Fig 2
Implant position on a lateral radiographic view. (A) Position of the
prosthesis is calculated on lateral view according to the distance between
posterior edge of the implant and posterior edge of the inferior vertebra. (B)
Example of prosthesis position in group 4–7 mm.
The prosthesis is inserted by a mini-invasive
anterior approach, with complete discectomy and release of the discal space.
The patient is positioned supine in the so-called “French position,” with legs
bent and open laterally. The surgeon stands between the legs facing the lumbar
spine in the cephalad-caudal direction, which is ergonomic for checking the
midline of the spine when approaching the L5-S1 and L4-L5 levels. The
assistant stands on the right or left side of the patient. The incision is
longitudinal or horizontal crossing the midline and 7 to 8 cm long. A
Pfannenstiel incision is more cosmetic for one-level surgery. After vertical
incision of the rectus abdominis sheath, the muscle is retracted laterally to
reach the common fascia of the external oblique muscle. The retroperitoneal
space is reached and the peritoneal sac retracted. The peritoneal sac is
pushed to the contralateral side with the ureter and the hypogastric plexus.
The vessel bifurcation is now exposed and analyzed. To reach L5-S1, the left
iliac vein must be carefully retracted and the medial sacral vessels ligated.
An opening to the anterior part of the L5-S1 disc of least 32 mm must be
exposed. At the L4-L5 level, the left approach is commonly used. The surgeon
must pay attention to the ascending lumbar vein, which is located at the
corner of the psoas belly and the left iliac vein. This important collateral
must be ligated. The segmental vessels at L4 and L5 must also be ligated to
allow retraction of the aorta and vena cava. Traction on the left iliac vein
must be controlled throughout the procedure. The anterior part of the disc is
opened according to the size of the templates. The anterior anulus and nucleus
are removed using disc rongeur, kerisson, curettes, and a scraper. The
posterior anulus must be opened to free the disc space and to allow good
restoration of the disc height. It is not necessary to open the posterior
longitudinal ligament, but it must be detached from the posterior border of
the end plates using the specific instruments. The mobility of the disc space
is tested with a spreader under C-arm control. The midline is checked with AP
fluoroscopy. A dedicated instrument is introduced in the disc space and makes
it possible to create a parallel distraction of the disc, thus restoring the
disk height. The upper or the lower keel cutter is slid onto a guide and
impacted into the vertebral body to prepare the bed for the fin of the
prosthesis. The prosthesis is impacted into the prepared disc space under
fluoroscopic control. The retractors are carefully removed and bleeding is
controlled. The rectus abdominis fascia and subcutaneous fat are closed with
drainage.
The implant (Maverick) is a metal-on-metal disc
prosthesis made of cobalt-chrome, with a ball-and-socket design. The
prosthesis has a fixed posterior center of rotation located below the lower
end plate. The production of wear debris is low and without epidural reaction
on animal studies.
All patients were seen postoperatively at 1, 3,
and 6 months and at 1 and 2 years. Pain was assessed using a VAS, neurologic
function, Oswestry scores, and the SF-36. Clinical success was taken to be a
25% improvement on the Oswestry score (ie, the success rate defined by the US
Food and Drug Administration [FDA] in a randomized prospective study
concerning the SB Charité prosthesis). Degree of patient satisfaction was
noted, as were need of analgesics and duration of treatment with analgesics or
anti-inflammatory agents. All patients received postoperative physiotherapy
from 1 week post surgery and wore a supple girdle for 6 weeks. Statistical
analysis was with the Student t test and the χ test.
Results
All patients underwent follow-up examinations. Oswestry score preoperatively and
at 2 years' follow-up was 43.8 and 23.1, respectively. Low back pain improved
from a mean VAS of 7.6 ± 1.7 preoperatively to 3.2 ± 1.8 at 2 years. Mean leg
pain VAS score decreased from 3.9 preoperatively to 2.1 at 2 years (P<0.05).
Mean daily duration of back pain decreased from 70% to 40% (P<0.05).
Daily duration of leg pain decreased from 36% to 20% (P<0.05). According
to the FDA criteria (>25% improvement of Oswestry score), the success rate was
75% (P<0.05). Improvement in back pain directly affected the improvement
in Oswestry score (P = 0.008) (Table 1).
Evolution of SF-36 score
was weighted according to sex and age of the patient. An improvement greater
than 15% was considered a success. Thus, 85% of patients experienced physical
improvement at 1 year, whereas improvement of mental health was noted in 43%.
The mean hospital stay
was 4.6 days (range, 3–10 days).
Complications
There were 4 cases of
postoperative root pain and 2 cases with sequelae from previous surgery (discectomies).
Seventeen patients received posterior facet infiltration (11 with a good
result). Three patients had spinal pain other than in the lumbar region. One
patient had a superficial infection treated by local debridement. There was
one visceral lesion due to the surgical incision, which was damage to a ureter
in a female patient operated several times for gynecologic problems. The
damage was successfully repaired and the orthopedic result was excellent.
Minor intraoperative complications were noted due to the surgical approach in
11 cases. There was never any breakage of the device. No implant had to be
removed or surgically revised.
Consumption of analgesics
was reduced overall because no patient needed any morphine-based drugs
postoperatively, whereas 62% were taking them preoperatively. With regard to
resumption of professional activity, 63% returned to work (the mean time to
return to work was 5 months; range, 2 months to 1 year). When the Oswestry
score was improved by 25% or more, there was a 44.4% chance of returning to
work. When the score improved 75%, the chance of returning to work was 73% (P
= 0.004). Factors influencing the clinical result in terms of success were as
follows: young age was associated with a good result (P = 0.05) and
female sex was associated with better results (P = 0.003).
Alternatively, previous spine surgery decreased the chance of having a good
result (P = 0.005), whereas being off work before the intervention did
not influence clinical outcome (P = 0.14).
Radiologic results
Mobility in flexion and
extension was 7.9° at discs L5-S1, 9.4° at L4-L5, and 7.4° at L4-L5 when there
was an arthrodesis at L5-S1 (Table 2). The coronal
position of the device was considered excellent in 51 cases (79.6%) and
satisfactory in 13 cases (20.4%); there was no insertion with an offset
superior to 19% (Table 3). The position of the implant
on lateral radiography was considered excellent in 57 cases (89%) and
satisfactory in 7 cases (11%) (Table 4). No implant
was inserted with a distance superior to 7 mm from the posterior wall of the
inferior vertebra. There was no correlation between satisfactory functional
outcome (Oswestry >25% and VAS >2 improvement) and the position of the device
based on the criteria applied in AP and lateral radiographs.
Postoperatively, the
device migrated axially 3 to 5 mm in the region of the superior end plate in
five patients (Fig. 3). Subsidence was stable at
l-year follow-up. The outcome was satisfactory in three of these patients,
with an Oswestry score averaging 14 and a VAS pain score of 2. For the other
two patients, one had a very poor result (Oswestry improvement zero) and the
other had a poor result (Oswestry improvement 10). There was no case of
anterior or posterior migration. Three patients had heterotopic ossification
(two type 1, one type 3 according to McAfee classification); all were mobile
on dynamic radiographs.
Fig. 3. Posterior
subsidence of the implant: 4 mm stable over time, with excellent clinical
Correlations between
improvement in Oswestry score and radiologically diagnosed criteria were as
follows: facet osteoarthritis grade 1 or 2 did not influence outcome (P
= 0.82); the presence of high intensity zones in the indication did not
influence outcome (P = 0.66); the presence of an osteophyte did not
influence outcome (P = 0.69); the presence of intradiscal gas did not
influence outcome (P = 0.34); and the presence of a change in Modic-type
1 or 2 signal in the indication did not influence outcome (P = 0.33).
Alternatively, certain
criteria influenced functional outcome: muscle degeneration grades 1 and 2 led
to a better outcome than grades 3 and 4 (P = 0.006); and absence of
McNab osteophytes on the spine other than at the operated region were
associated with success (P = 0.003).
The position of the
implant on AP radiographs did not influence outcome when the implant was
situated between 0% and 19% (P<0.05). The position of the implant on
lateral view radiographs did not influence outcome when the implant was
situated between 0 and 7 mm from the posterior wall of the inferior vertebra (P<0.05).
Discussion
Discectomy with insertion
of total disk prosthesis has been widely reported to improve the clinical
symptoms of chronic back pain. The degree of improvement is equivalent to that
obtained with anterior fusion cages using the mini-invasive technique.
Radiographic follow-up in the authors' series showed a degree of mobility
close to normal and confirms the results obtained with other devices such as
the SB Charité (Depuy,
USA),
as reported by many authors, and with the Prodisc (Synthes,
Switzerland),
as reported by Bertagnoli and Kumar and Mayer et al. The
technique is safe because the intra- and postoperative complication rate is
low and equivalent to other series. The patients recover rapidly, and the mean
hospital stay of 3 to 5 days is similar to the results reported by Bertagnoli
and Kumar and Lemaire et al but in contrast to
8 to 12 days for an arthrodesis reported by Katz. The Oswestry
score improved for 75% of patients; this improvement is significantly
correlated with facet arthrosis and fatty muscle degeneration. It has been
demonstrated that the disc degenerates before the facets, but facet arthrosis
could be a limiting factor for total disc replacement, particularly in
adjacent level disease after fusion. This study is the first to show that a
semiconstrained implant with a fixed posterior center of rotation can be
implanted with grade 1 and 2 facet arthrosis with a good clinical outcome.
This result seems to confirm the work of Dooris et al
showing that a posterior center of rotation lightens the load on the facets.
This study is also the first to show a relationship between muscle fatty
degeneration and clinical results because the greater the amount of fat, the
less satisfactory the result. Contrary to the posterior approach, the anterior
implantation technique does not damage the spinal muscles and shortens the
delay until activity can be resumed.
The SF-36 physical score
improved more than the mental score, similar to the prospective randomized
study results using the SB Charité device.
The position of the
implant on AP and lateral radiographs was satisfactory with the instruments
used; all were implanted in good or excellent position. The functional outcome
(Oswestry and VAS scores) did not correlate with the implant position when the
device was implanted in a safety region demarcated on coronal and lateral
views, respectively, as defined in the protocol. Outside this safe area, the
results could be different; however, there were no data to confirm this.
In summary, a
semiconstrained device with a fixed center of rotation is a biomechanical
tradeoff for obtaining a very good clinical outcome, providing the device is
implanted within the safety margins previously outlined. This report is the
first to show such an outcome. Other disc prosthesis designs were less
successful in the past.
Disc prostheses offer the
prospect of earlier treatment of certain recalcitrant chronic back pain
without having recourse to an arthrodesis. It is always possible to revert to
an arthrodesis if results are poor or if there is progressive degeneration of
the posterior structures. A few cases of arthrodesis with posterior fixation
and a posterolateral graft have been reported by Lemaire et al for treating
patients whose pain is recalcitrant. The failure may be due to a technical
error or to an erroneous indication, so patients should be selected according
to very rigorous criteria. Le Huec et al proposed guidelines that take into
account the characteristics of not only the pathologic level (disk and
posterior elements) but also the adjacent levels. The spontaneous fusion of
certain prostheses has been reported by Lemaire et al, a problem always
accompanied by intraprosthetic calcification. One solution is to prescribe
postoperative nonsteroidal anti-inflammatory drugs, as in hip prostheses.
Another solution is to limit the bleeding of the vertebral end plates by
applying a hemostatic agent on the bony tissue not covered by the prosthesis.
Even heterotopic calcifications allowed the prosthesis to be mobile in three
of the authors' cases. Based on the McAfee classification, it is not possible
to know whether these patients will reach grade 4 calcification and,
therefore, lose their mobility. The metal-on-metal couple seems very safe as
demonstrated by animal studies and previous work in total hip replacement by
Jacobs et al and Haynes et al. The quantity of wear
debris produced by a metal-on-metal implant is low compared with
metal-on-polyethylene prostheses. Le Huec et al showed that there was no
shock absorption difference between metal-on-metal and metal-on-polyethylene
disc prostheses in physiologic conditions. Prosthesis dislocation has been
reported for Prodisc and SB Charité prostheses but not with the Maverick
implant. The design of the Maverick in respect to fundamental criteria
proposed by Hedman et al and Dooris is likely very important regarding the
biomechanics.
Summary
The metal-on-metal
Maverick device with a posterior center of rotation and controlled translation
is a promising therapeutic technique (Fig. 4). Its
mechanical characteristics and resistance to wear make it an interesting
option in terms of its life cycle. Only long-term follow-up exceeding 5 years
will make it possible to confirm these favorable preliminary results and to
analyze the effects on the segments adjacent to the operated levels. This
series shows that for one-level degenerative disc disease, the early results
are equivalent to the best anterior lumbar interbody fusion series, with a low
complication rate. Total disc replacement could offer benefit by preventing
adjacent-level disease because of decreased stress on the adjacent disc after
the sagittal balance is restored
Fig. 4. Excellent
position on anteroposterior and lateral views with excellent clinical outcome.
PII: S0030-5898(05)00009-X
doi:10.1016/j.ocl.2005.02.001
© 2005 Elsevier Inc.. All rights reserved
This study has bee re-formatted for web
reproduction, tables and links have been removed to facilitate this process.
Find the entire study at
http://www.orthopedic.theclinics.com/article/PIIS003058980500009X/fulltext
Back to GetADR home
ProDisc II Study
Clinical Results of Total Lumbar Disc Replacement With ProDisc II: Three-Year Results for Different Indications.
Clinical Case Series
Spine. 31(17):1923-1932, August 1, 2006.
Siepe, Christoph J. MD; Mayer, H Michael MD, PhD; Wiechert, Karsten MD; Korge, Andreas MD
Abstract:
Study Design. Prospective study analyzing midterm clinical results of total lumbar disc replacement (ProDisc II) for different indications.
Objectives. To assess functional outcome after total lumbar disc replacement (TDR) treated for varying indications.
Summary of Background Data. Despite its frequent use and increasing popularity, indications and contraindications for TDR have not been defined precisely at this stage and remain a matter of debate, leading to disc replacement procedures in a variety of pathologies that have not yet been evaluated and compared separately.
Methods. Patients meeting inclusion criteria were evaluated prospectively according to Visual Analogue Scale (VAS), Oswestry Questionnaire, SF-36, and numerous clinical parameters. Indications included degenerative disc disease (DDD), DDD with accompanying soft disc herniation (nucleus pulposus prolapse, NPP), osteochondrosis following previous discectomy, and DDD with presence of Modic changes. Postoperative improvement was recorded and analyzed for influence of preoperative diagnosis.
Results. Overall, 92 patients from four groups with a mean follow-up of 34.2 months (minimum, 24 months) achieved significant and maintained improvement from preoperative levels (P < 0001). Patients with DDD + NPP achieved results significantly better than patients from the other groups (P < 0.05). Presence of Modic changes or previous discectomy did not influence outcome negatively. Improvement was achieved for both monosegmental and bisegmental disc replacements (P < 0.05), nevertheless with significantly inferior results for bisegmental interventions at 12- and 24-month follow-up and considerably higher complication rate. While older patients were still highly satisfied with postoperative outcome, better functional outcome was observed in younger patients.
Conclusion. Present data suggest beneficial clinical results of TDR for treatment of DDD in a highly selected group of patients. Better functional outcome was obtained in younger patients under 40 years of age and patients with degenerative disc disease in association with disc herniation. Multilevel disc replacement had significantly higher complication rate and inferior outcome. Results are significantly dependent on preoperative diagnosis and patient selection, number of replaced segments, and age of the patient at the time of operation. Because of significantly varying outcomes, indications for disc replacement must be defined precisely.
Results
Overall results are outlined in Table 2 . In 92 patients that received total lumbar disc replacement with ProDisc II, a total of 108 disc prosthesis were implanted. Thirty-three (35.9%) of the patients were male, and 59 (64.1%) were female. The average age of the patients was 42.5 years (range, 21.9-66.1 years; SD, 9.1 years) with an even age distribution over all groups.
The operations were performed monosegmental (n = 77; 83.7%), bisegmental (n = 14; 15.2%), or multisegmental (3 levels, n = 1; 1.1%); operated levels are outlined in Table 2 . Monosegmental operations were predominantly performed at the lumbosacral junction (n = 59; 64.1%) and at the segment floating above the lumbosacral junction (n = 17; 18.5%). Including multisegmental procedures performed at the lumbosacral junction (n = 15; 16.3%), the lumbosacral motion segment was involved 74 times (80.4%).
Intraoperative/Perioperative Data
The overall operating time averaged 115 minutes for monosegmental operations (range, 58-210 minutes; SD, 32 minutes) and 190 minutes for bisegmental procedures (range, 103-300 minutes; SD, 46 minutes). The recorded volume of blood loss averaged 100 mL over all groups (range, 10-350 mL; SD, 65 mL). Patients were mobilized from the first postoperative day without additional support. There were no significant differences for intraoperative data between the different groups.
Group Analysis
Results for preoperative levels of VAS and ODI as well as postoperative improvement for different indications are outlined in Table 3 . With the exception of the VAS for Groups 2 and 3 (P = 0.04), there were no significant differences before surgery between the different groups.
Patients from all groups as well as combined data showed highly significant postoperative improvement for VAS and ODI scores and were able to maintain these results until last follow-up (P < 0.001; Figure 3). For Groups 1, 3, and 4, we were able to detect a minor decline for both ODI and VAS scores from 36-month to 48-month follow-up. Nevertheless, postoperative improvement was still significant (P < 0.05).
 |
Figure 3. (click image to zoom)
Postoperative results for VAS (A) and ODI (B) for different indications over time. DDD = degenerative disc disease; NPP = nucleus pulposus prolapse. Student's t test was performed to compare preoperative with postoperative data (VAS, ODI) for Groups 1-4. P < 0001 for all groups and combined data. |
Forty patients with DDD and without any other accompanying pathologies (Group 1) were used as a reference for comparison with the remaining groups.
Modic changes were seen in 23 patients. Presence of Modic changes did not have any significant influence on overall outcome compared with patients from Group 1.
Similarly, no significant difference could be detected between a preselected group of patients that had previously undergone discectomy and those without (comparison Group 1 vs. Group 3; P > 0.3). Sciatica in this group was present before surgery in 12 out of 17 patients and improved in 8, leaving 4 patients with no benefit as regards their leg pain. Sciatica was not caused in any of the patients from this group nor did preexisting radicular leg pain deteriorate as a cause of disc replacement after previous surgical intervention.
Overall, postoperative differences between Groups 1, 3, and 4 were not statistically significant. Best results were achieved for patients with DDD and coexisting contained soft disc herniation (Group 2, Figure 4). Results for postoperative VAS, ODI, as well as overall improvement at last follow-up for patients from this group were significantly superior to Groups 1, 3, and 4 (P < 0.05). Excellent results were maintained throughout the postoperative course with a mean follow-up of 33.1 months. All patients (n = 12; 100%) reported highly satisfactory outcome and would retrospectively opt for an operation again.
 |
Figure 4. (click image to zoom)
Disc replacement in a patient with back pain from symptomatic disc degeneration and accompanying central disc herniation at L5-S1 (A and B). Signs of adjacent disc degeneration at L4-L5. (C and D) Radiograph at the 36-month follow-up shows retained disc height at L4-L5 and satisfactory implant positioning. Clinically, the patient experienced significant and lasting improvement from his previous complaints. |
Subjective Outcome Evaluation
Asked for their subjective evaluation of total disc replacement, 65.2% of the patients were completely satisfied at the time of their last follow-up and recorded their result as excellent, 17.4% were satisfied and marked good results, and another 17.4% of the patients were not satisfied with their personal outcome ( Table 2 ).
Thus, 82.6% of the patients were satisfied or highly satisfied overall, which is reflected in the amount of 85.7% of patients that would retrospectively undergo disc replacement operation again; 12.7% of the patients would not decide for a repeat operation, while 1.6% of the patients were unsure. These results are in continuity with our previously published preliminary data.[22]
Monosegmental Versus Bisegmental Operations
Comparing monosegmental versus bisegmental disc replacements, statistical analysis showed significant improvement for both groups at 3- and 6-month follow-up as regards evaluation of VAS and ODI scores (P < 0.001) (Figure 5). While patients with monosegmental disc replacements were able to maintain excellent results throughout the postoperative course showing highly significant postoperative improvement for VAS and ODI (P < 0.001), a deterioration in the results was noted for bisegmental operations 12 and 24 months after surgery. As for ODI scores, there was still a strong tendency toward significant improvement from preoperative level at 12 and 24 months after surgery (P = 0.07), and improvement for VAS was still statistically significant (P = 0.01). Nevertheless, there was a significant difference comparing outcome of bisegmental TDR with monosegmental operations at 24 months after surgery (P = 0.02 for VAS; P = 0.01 for ODI, Mann-Whitney U-Wilcoxon rank sum test).
 |
Figure 5. (click image to zoom)
Postoperative development and comparison of VAS (A) and ODI (B) for monosegmental versus bisegmental disc replacements. ODI = Oswestry Disability Index; VAS = Visual Analogue Scale; TDR = total lumbar disc replacement. (A) +P = 0.01 paired t test, comparison of preoperative versus postoperative bisegmental TDR. oP < 0.001 paired t test, comparison preoperative versus postoperative monosegmental TDR. #P = 0.02 Mann-Whitney Test for comparison of monosegmental versus bisegmental TDR at 24 months postoperation. (B) +P = 0.07 paired t test, comparison of preoperative versus postoperative bisegmental TDR. oP < 0.001 paired t test, comparison of preoperative versus postoperative monosegmerntal TDR. #P = 0.01 Mann-Whitney test for comparison of monosegmental versus bisegmental TDR at 24 months postoperation. |
From a clinical point of view, this can be backed up by patient satisfaction rates. While 85.7% of patients with monosegmental disc replacements reported good and excellent subjective results, this is opposed to only 64.3% of patients after bisegmental disc replacement at the time of last follow-up.
Level of Disc Replacement
To evaluate the influence of the level of disc replacement on postoperative outcome, data for VAS and ODI from patients with monosegmental disc replacements performed at the lumbosacral junction were compared with disc replacements performed at the level above the lumbosacral junction. The number of patients and level of disc replacements is outlined in Table 2 . No significant difference was observed between the two groups, neither before surgery nor at any stage throughout the postoperative course. There was a trend toward better outcome for ODI for disc replacements performed at the level above the lumbosacral junction. However, statistical testing did not reveal any significant difference (P > 0.05).
Back to Work
At the last follow-up, 56.0% of the patients were back in their old working environment without restrictions in full time labor, while 4.4% were back in their old job but on a limited time scale; 7.7% of the patients had reorganized their professional life after surgery and found themselves in a new working environment.
Overall, 29% of the patients were on sick leave already before surgery, but only 1.1% of these were not able to benefit as regards their working status; 15.4% of the patients received Workers' Compensation, 3.3% received an old-age pension, and 12.1% of the patients were recorded as unemployed at last follow-up due to economic reasons despite the fact that from a medical point of view the patients were in a good condition.
Thus, the overall rate for patients being back in their old job or some kind of modified professional activity at their last visit summed up to 68.1% following TDR.
Age
Analyzing age from 92 patients, we found an even age distribution over all groups. This cohort was further subdivided according to age into five different subgroups by decades starting from the age of 20 to analyze influence of age on clinical outcome. Because of the small number of patients 20 to 30 years of age and ≥60 years of age, these groups were not used for statistical analysis, leaving three age groups (30-40, 40-50, and 50-60 years, respectively). Patients from each group similarly showed significant improvement for VAS, ODI, and good to excellent subjective patient evaluation (P < 0.05; Table 4 ).
Comparing postoperative results from patients 40 to 50 years of age with patients 50 to 60 years of age, we did not find any statistical significance. Best results were achieved for patients 30 to 40 years of age at the time of the operation. Postoperative improvement for VAS and ODI was significantly better in this age group compared with patients 40 to 50 or 50 to 60 years of age. Nevertheless, subjective outcome evaluation still showed highly satisfactory results, with 93.3% of patients 50 to 60 years of age reporting good to excellent clinical outcome at last follow-up.
Complications
Complications are listed in Table 5 . The overall complication rate was 19.6%, requiring revision surgery at the index level in 8.7% of the patients and another 2.2% at the non-index level following TDR. There were no vertebral body fractures as reported previously by other authors. Furthermore, there were no direct vessel lacerations in any of the patients. Complication rate was considerably higher for bisegmental disc replacements (n = 5 of 14 operations; 35.7%) compared with monosegmental interventions (n = 11 of 77; 14.3%).
Charite Study - 10 years follow-up Charite
International
Symposium - Swiss Spine Institute
Program Study, June 22, 2002,
09.45h
Scientific Session 3
Long Term Results with the SB Charite
Artificial Disc
Jean-Pilippe
Lemaire, MD
100 patients (41 males, 59
females) with a mean age of 50.9 years (35.2-62.1) are studied after 10 years
follow-up. 43% had a sedentary work, 37% light work and 19% heavy work, 44% had
previous surgery.
The clinical results was
analyzed according to a modified Beaujon scale, including the delay and the
quality of return to work. Radiological results describe 3 factors, anatomic,
kinematic and biomechanic (lordosis and balance). 62% have an excellent clinical
result, 28% good results and 10% poor results. This percentage can be compared
with results of same patients at 51 months follow up, and allow to discuss the
factors improving the indications and results.
80% of the patients return to
the same work, 77.7% of the light workers, 63.2% of the heavy workers.
Radiological, there is no modifications of the prothesis, no loosening, no cold
flow of the polyethylene. The loss of mobility is of 10% with a mean value of 10
degrees. The prosthesis restore the lordosis and the sagittal balance of the
lordosis. There is 9% of complications, but real complications of the prosthesis
are 2%, the others being complications of any anterior approach.
The FDA Trial results
|
DEPARTMENT OF HEALTH AND HUMAN
SERVICES
|
PMA
MEMORANDUM |
|
Division of General, Restorative and
Neurological Devices
Orthopedic Devices Branch, HFZ-410
(301) 594-2036 |
Food and Drug Administration
Office of Device Evaluation
Center for Devices and Radiological Health
9200 Corporate Boulevard
Rockville, MD 20850 |
|
Charité™ Artificial Disc
DePuy Spine
325 Paramount Drive
Raynham, MA 02767-0350 |
CLINICAL REVIEW
SUMMARY
The subject device is the Charité™ Artificial
Disc, consisting of two CoCrMo alloy endplates and an UHMWPE core, indicated for
spinal arthroplasty in patients with single-level lumbar degenerative disc
disease (DDD) from L4 to S1. The sponsor conducted a
non-inferiority randomized, prospective clinical trial comparing the clinical
results of treatment with the subject device and anterior interbody fusion using
the BAK fusion cage. The study demonstrated that the Charité™ Artificial Disc
is safe and effective in the treatment of lumbar DDD compared to anterior
interbody fusion with the BAK cage.
REVIEW
The subject of this review is
P040006, the clinical module for M020026/M003,
dated 2/13/04 and received 2/13/04.
Regulatory History
The Modular Shell was approved 3/4/03. The
first module, M001, was filed on 3/12/03. The second module, M002, was filed
4/17/03.
CLINICAL INFORMATION
The subject device (as well as previous design
versions) has been commercially available in other countries since 1987. The
sponsor estimates that over 7,000 patients worldwide have received a Charité
Artificial Disc replacement. The Waldemar Link Company in Hamburg, Germany is
manufacturer of the device.
CLINICAL TRIALS
INVESTIGATIONAL PLAN
The sponsor states that five versions of the
protocol were utilized in this study. The sponsor provided a summary of the
changes in Volume 14, pp.1-8. The
investigational plan is summarized below
with the protocol changes noted in the applicable section.
Purpose
The stated purpose of the investigation is to
evaluate the safety and effectiveness of the
SB Charité™ III (SB III) compared to the BAK
Interbody Fusion Device (BAK Cage) for the treatment of single-level
degenerative disc disease, as per 21 CFR
812.25(a). The sponsor makes no unsubstantiated statements about expected
outcomes and makes no concluding statements about the safety or effectiveness of
the device.
Study Design
The sponsor proposed
a randomized, prospective, multicenter clinical trial consisting of
341
patients with single-level
DDD of the lumbar spine (L4L5
or L5S1) in patients who have not previously received
surgical treatment, except for a prior discectomy, laminotomy, or nucleolysis at
the same level, and have failed to improve with conservative treatment for at
least 6 months prior to enrollment. After
enrollment, the patients will be randomized
in a 2:1
ratio to two treatment groups:
SB III or BAK
control. Each investigational site has an
independent block
randomization schedule.
There will be a maximum of 15 investigational sites. The first 5 patients at
each investigational site will not be randomized but will all receive the SB III
device.
Controls
(Volume 14, Section 8.13.1.1,
p.12)
The patients randomized to the control
treatment will undergo lumbar interbody fusion with a BAK cage.
Intended Use
“The
Charité
Artificial Disc
is
indicated for spinal arthroplasty in skeletally mature patients with
degenerative disc disease (DDD) at one level from L4 to S1.
DDD is defined as discogenic back pain with degeneration of the disc confirmed
by patient history and radiographic studies. These DDD patients may also have
up to 3mm of spondylolisthesis at the involved level. Patients receiving the
Charité Artificial Disc should have had at least 6 months of conservative
treatment prior to implantation of the Charité Artificial Disc; these treatments
may include discectomy, laminotomy/ectomy (without accompanying facetotomy), or
nucleolysis at the same level to be treated.”
Device Description
The subject device is the Charité™ Artificial
Disc. The device consists of two endplates manufactured from CoCrMo alloy (ASTM
F75) and an UHMWPE sliding core (ASTM F648). The bi-convex core articulates
between the two concave endplates. The endplates are available in 5 sizes, and
each size is available in 4 angles: plane-parallel (0ْ) and oblique (5ْ, 7.5ْ,
and 10ْ). The undersurface of the endplates is slightly convex and has 6
tooth-like projections that anchor the plates to the bone. The UHMWPE core is
available in 5 diameters, and each is available in 5 heights for sizes 1-3, and
4 heights for sizes 4-5. The core also has a radio-opaque CoCr alloy wire for
x-ray visualization.
|
Charite Endplates |
|
Size |
AP width (mm) |
Lateral width (mm) |
Angles (degrees) |
|
1 |
23 |
28.5 |
0, 5, 7.5, 10 |
|
2 |
25 |
31.5 |
0, 5, 7.5, 10 |
|
3 |
27 |
35.5 |
0, 5, 7.5, 10 |
|
4 |
29 |
38.5 |
0, 5, 7.5, 10 |
|
5 |
31 |
42.0 |
0, 5, 7.5, 10 |
|
Charite Cores |
|
Size |
Diameter (mm) |
Heights (mm) |
|
1 |
23 |
7.5, 8.5, 9.5, 10.5, 11.5 |
|
2 |
25 |
7.5, 8.5, 9.5, 10.5, 11.5 |
|
3 |
27 |
7.5, 8.5, 9.5, 10.5, 11.5 |
|
4 |
29 |
8.5, 9.5, 10.5, 11.5 |
|
5 |
31 |
8.5, 9.5, 10.5, 11.5 |
There were three generations of the subject
device: Charité I, Charité II, and Charité III. The Charité I and II devices
had 1mm thick stainless steel endplates. The Charité I device was implanted in
13 patients beginning in 1984, but had a problem with endplate subsidence,
attributed to the small surface area of the implant. The Charité II had a new
oval-shaped endplate design with a large surface area, and these were implanted
in 58 patients beginning in 1985. However, the endplates of these devices
fractured, and this problem was attributed to the non-forged stainless steel
material. The Charité III design was introduced in 1987. The device design
incorporated changes in endplate material (CoCrMo alloy); number, shape and
position of the endplate teeth; addition of additional endplate sizes and
angles; and changes in the core shape and size. The device has been named the
SBIII, SBC, Link SBC, and others. In June 2003, DePuy Spine acquired the
device.
Statistical Plan
The study
has been designed as a non-inferiority trial.
Success definition:
The protocol (Volume 2, p.38) states that the
individual patient will be determined to be a success if all of the following
are found:
1.
Improvement in the Oswestry Disability Index ≥25% at 24 months compared
to the score at baseline.
2.
No device failures requiring revision, re-operation, or removal.
3.
Absence of major complications, defined as major blood vessel injury,
neurological damage, or nerve root injury.
4.
Maintenance or improvement in neurological status at 24 months, with no
new permanent neurological deficits compared to baseline.
The study was designed as a non-inferiority
trial with a δ = 0.15.
H0: μs ≥ μt +
δ H1: μc < μt + δ
μs: Clinical success rate
in the BAK Cage Control group
μe: Clinical success rate
in the SB Charité™ III group
δ: Clinically significant difference
between the treatment groups. δ = 0.15
Because the δ includes
confidence intervals, the observed success rate for the SB Charité™ III group
could be no more that 4.9% lower than the success rate for the BAK Cage Control
group to conclude that the two groups are equivalent.
Sample Size Justification:
The sponsor assumed a 70% success rate for both
treatment groups.
δ = 0.15
α = 0.05
β = 0.80
The estimated sample size was 174 patients for
the treatment group and 87 patients for the control group, or 261 patients
total. With a 10% dropout rate, the treatment group sample size is 194 patients
and the control group is 97 patients, for a total of 291 patients. Assuming 5
training cases per site at 15 sites, the total is 366 patients (269
investigational and 97 control).
Analysis Populations:
The sponsor also defined the following
populations for analysis:
·
Intent-to-Treat (ITT) population:
all patients who were randomized in the study and had either a 24-month
follow-up evaluation or had been declared an “early discontinuation” (i.e., lost
to follow-up). Patients who were not yet due for follow-up or those who were
overdue for the 24-month evaluation were not included in the ITT group.
·
All Randomized Subjects
population: all patients enrolled.
·
Completers population: patients
who were evaluated at 24 months regardless of whether the visit was within the
defined evaluation time window (22 months to 26 months)
·
Completers In-Window population:
patients who had the 24-month evaluation within the defined evaluation time
window (22 months to 26 months)
·
Safety population: all patients
who were randomized and received treatment.
Missing Data:
Patients with incomplete or missing data were
classified as failures for the efficacy analysis. Missing values were ignored
for the analysis of secondary endpoints, summaries of baseline characteristics,
and other summaries.
Endpoints
Primary Endpoints:
·
Oswestry Score (μ) at 24-months or
later.
Secondary Endpoints:
·
Pain VAS improvement of ≥20mm
·
SF-36 improvement ≥15%
·
Disc height (lateral x-ray)
·
Displacement or migration of the
device
·
Radiolucency around the implant
for Charité patients at 24 months
Interim Analyses
None.
Inclusion/Exclusion Criteria
(Volume 14, pp.17-14)
|
Inclusion |
Exclusion |
|
·
Male or female
·
Age 18-60 years
·
Symptomatic degenerative disc
disease with objective evidence of lumbar DDD by CT or MR scan, followed by
discogram
·
Single level disease at L4L5
or L5S1
·
Minimum of 6 months of
unsuccessful conservative treatment
·
Oswestry Low Back Pain
Disability Questionnaire ≥30 points
·
Patient a surgical candidate
for an anterior approach to the lumbar spine (<3 abdominal surgeries)
·
Back pain at the operative
level only (by discogram)
·
Leg pain and/or back pain in
the absence of nerve root compression, per MRI or CT scan, without prolapse
or narrowing of the lateral recess.
·
VAS ≥40mm
·
Able to comply with protocol
·
Informed consent
DDD is defined as discogenic
back pain with degeneration of the
disc as confirmed by history and radiographic studies with one or more of
the following factors:
o
Contained herniated nucleus
pulposus
o
Facet joint
degeneration/changes
o
Decreased disc height by ≥2mm,
and/or
o
Scarring/thickening of
ligamentum flavum, annulus fibrosus, or facet joint capsule
|
·
Previous or other spinal
surgery at any level, except prior discectomy, laminotomy, laminectomy, or
nucleolysis at the same level
·
Multiple level degeneration
·
Previous trauma to the L4,
L5, or S1 levels in compression or burst
·
Non-contained or extruded
herniated nucleus pulposus
·
Mid-sagittal stenosis of <8mm
(by CT or MR)
·
Spondylolisthesis >3mm
·
Lumbar scoliosis (>11ْ sagittal
plane deformity)
·
Spinal tumor
·
Active systemic or surgical
site infection
·
Facet joint arthrosis
·
Arachnoiditis
·
Isthmic spondylolisthesis
·
Chronic steroid use
·
Metal allergy
·
Pregnancy
·
Autoimmune disorders
·
Psychsocial disorders
·
Morbid obesity (BMI >40)
·
Bone growth stimulator use in
spine
·
Investigational drug or device
use within 30 days
·
Osteoporosis or osteopenia or
metabolic bone disease
·
Positive single or bilateral
straight leg raising test
|
Study
Treatments (Volume 14, Section
8.13.1.1, p.22)
SB
Charité™ III Treatment Group
All investigational group patients will undergo
a discectomy and implantation of the SB Charité™ III device through an anterior
retroperitoneal approach
BAK
Interbody Fusion Device Control Treatment Group
Patients randomized to the control group will
have an anterior lumbar interbody fusion at one or two contiguous levels (L2-S1)
with autogenous bone grafting and stabilization with the BAK Cage using the
anterior retroperitoneal approach.
Postoperative
Protocol
The investigational and control groups will have
the same postoperative protocol. Lumbar strengthening (“stabilization therapy”)
begins at 2-4 weeks postop. No lifting or bending for 6 months.
Evaluations
(Volume 14, Section 8.31.1.1, pp.23)
The protocol specifies that patient assessments will be performed
preoperatively, and postoperatively prior
to discharge, 6 weeks (±2 weeks), 3 months
(±2 weeks), 6 months
(±1 month), 12 months
(±1 month),
24 months (±2 months) (schedule of evaluations, Section 8.4.1, Table 9).
Clinical
Evaluation
The following
clinical
assessments will be performed:
·
Work status: Baseline, 6 wks, 3
mo, 6 mo, 12 mo, 24 mo
·
Visual Analog Scale (VAS) for
Pain: Baseline, 6 wks, 3 mo, 6 mo, 12 mo, 24 mo
·
Oswestry Disability Index (ODI):
Baseline, 6 wks, 3 mo, 6 mo, 12 mo, 24
mo
Each question is scored on a 6-point scale. The
responses are added, then doubled, and expressed as a percentage. ODI are rated
as follows: 0-20 minimal disability; 20-40 moderate disability; 40-60 severe
disability; and >60 severely disabled/bed-bound.
·
SF-36
Health Related
Quality of
Life
Survey: Baseline, 6 mo, 12 mo, 24 mo
Neurological status: Baseline, 6 wks, 3 mo, 6
mo, 12 mo, 24 mo
·
Range of Motion: Baseline, 6 mo,
12 mo, 24 mo
·
History and physical examination:
Baseline, 24 mo
·
Adverse events:
Postop, 6 wks, 3 mo, 6 mo, 12 mo, 24 mo
Radiographic
Evaluation
·
X-rays—AP, lateral,
flexion/extension laterals: Within 6 mo
of enrollment, postoperatively at 6 wks, 3 mo, 6 mo, 12 mo, 24 mo
All
radiographs will be evaluated by the investigator and another evaluator at that
investigational site. If there disagreements, a third evaluator will review the
films. In the 4/5/00 protocol version, the protocol was modified to require all
radiographic evaluations to be performed by a core laboratory. The radiographic
evaluation protocol was provided in Volume 14, Section 8.13.1.2. The
recommended radiographic technique was provided. The radiographs are scanned
into the computer, and all calculations are made with the BioQuant Image
Analysis System software program.
The radiographic criteria for fusion were
defined as follows:
-
Absence of radiolucent lines around ≥50% of the assembly
-
Translation motion <3mm (on flexion/extension), and
-
Angulation motion <5 degrees (on flexion/extension)
Device migration or displacement was defined as
movement >3mm (the measurement error for plain radiographs).
U.S.
CLINICAL TRIAL RESULTS
Two related U.S. studies of the subject device
are described below. The Pivotal Study was the prospective, randomized,
controlled, multicenter IDE clinical trial. The Continued Access Study was the
prospective, uncontrolled, multicenter registry of patients implanted with the
device under continued access. For the Pivotal Trial, the database closure date
was 1/16/04.
|
Summary of U.S. Clinical Trials |
|
|
Pivotal Study |
Continued Access Study |
|
Design |
Multicenter
Training arm (5 pts/site)
Randomized arm
·
2:1 investigational:control
24-month follow-up |
Multicenter
Registry
24-month follow-up |
|
Sites |
15 |
15 |
|
Subjects |
Approved: 194:97 + 75 training cases
375 enrolled
·
71 training arm (Charité)
·
205 randomized (Charité)
·
99 randomized (BAK control) |
615 approved
350 enrolled (approximately)
71 (with >12 months follow-up) |
|
Enrollment period |
Training: 3/21/00 – 5/22/01
Randomized: 5/16/00 – 4/24/02 |
5/17/02 to present |
|
Investigational Rx |
Charité Artificial Disc |
Charité Artificial Disc |
|
Control Rx |
BAK Cage |
None |
Study
Population
There were 71 training patients implanted with
the Charité Artificial Disc. There were
304 randomized patients, 205 implanted with the Charité Artificial Disc and 99
fused with the BAK Cage. In addition, there were 71 patients implanted with the
Charité Artificial Disc in the continued access study. The training cases will
be analyzed separately from the randomized patients.
The sponsor divided the patients into two
analysis groups: the Intent-To-Treat (ITT) group and the All Randomized Subjects
group. The ITT group consists of all treated patients who were treated with
only the patients who died or were discontinued. The All Randomized Subjects
group consists of all patients enrolled into the study. The All Randomized
Subjects analysis group consists of 304 patients (205 Charité patients and 99
BAK patients). The ITT group consists of 267 patients (182 Charité patients and
85 BAK patients).
The mean age of the study group was 39.5 years
(19-60 years) in the Charité group, and
40.1 years (20-60 years) in the BAK group.
There were 83 (46%) men and 99 (54%) women in the
Charité group and 47 (55%) men and 38 women
(45%) in the BAK group. The demographic
data are reproduced in the following table.
|
ITT Population Characteristics |
|
|
Charité Artificial Disc |
BAK Cage |
|
N |
182 |
85 |
|
Sex, Men (%)
Women (%) |
83 (46%)
99 (54%) |
47 (55%)
38 (45%) |
|
Age, mean
Range |
39.5
19-60 |
40.1
20-60 |
|
Age Category >45 years
Age Category ≤45 years |
41 (23%)
141 (77%) |
28 (33%)
57 (67%) |
|
Level L4L5 |
53 (29%) |
28 (33%) |
|
Level L5S1 |
129 (71%) |
57 (67%) |
There was no significant difference in the
duration of prior conservative treatment for DDD: 33.7 months for the
Charité group and 27.0 months for the BAK
group. There were 62 patients (34%) in the Charité group and 27 patients (32%)
in the BAK group who had undergone previous surgical treatment (Appendix 1,
Table 13.1). There was one patient in each group (2% and 4%, respectively) who
had osteoporosis based on DXA.
Surgical variables
|
ITT Surgical Procedures |
|
|
Charité Artificial Disc |
BAK Cage |
|
N |
182 |
85 |
|
Level L4L5 |
53 (29%) |
28 (33%) |
|
Level L5S1 |
129 (71%) |
57 (67%) |
The operative times were 111 minutes and 115.3
minutes, respectively for the Charité and
the BAK groups (p=0.5462). The estimated
blood loss was 207cc and 224cc, respectively
(p=0.6012).
For the Charité group, the implant
configurations (craniad/caudad endplates) were as follows: 109 oblique/oblique;
12 oblique/parallel; 54 parallel/oblique; and 30 parallel/parallel. The implant
component sizes were as follows:
|
Charite Artificial Disc Implanted
(Table 17.2) |
|
Size |
Cephalad Endplates |
Caudad Endplates |
Core |
|
|
Parallel |
Oblique |
Parallel |
Oblique |
|
|
1 |
0 |
0 |
0 |
0 |
0 |
|
2 |
6 |
11 |
6 |
11 |
17 |
|
3 |
54 |
77 |
24 |
107 |
131 |
|
4 |
24 |
33 |
12 |
45 |
57 |
|
5 |
0 |
0 |
0 |
0 |
0 |
For the
99 randomized control group patients, the cage sizes were as follows:
|
Lengths:
61 20mm
24 24mm |
Diameters:
1 11mm
17 13mm
50 15mm
17 17mm |
Patient Accounting
There were 177
Charité
patients (86%) and 78 BAK patients (79%) who were evaluated at 24 months. There
were 5 (3%) and 7 (8%) patients, respectively, who discontinued early from the
study for the following reasons: patient non-compliance (6), voluntary
withdrawal (3), lost to follow-up (left the U.S.) (1), patient refusal (1),
death (1). There were 18 patients (10
Charité and 8 BAK) who were overdue for
their 24-month evaluation, and 19 patients (13
Charité
and 6 BAK) who were not yet due for the 24-month follow-up.
Of the 205 Charité patients, 3 patients had not reached the 24-month evaluation
time point at the time of database closure, 1/16/04. Therefore, the theoretical
number of patients due at the 24-month time point for the Charité group was 202
patients.
|
Patient Populations |
|
|
Randomized Study |
Continued Access |
|
Training Arm |
Charité Artificial Disc |
BAK Cage |
|
Enrolled |
71 |
205 |
99 |
71 |
|
All Randomized |
|
205 |
99 |
|
|
Not overdue for 24-month |
|
13 (6%) |
6 (6%) |
|
|
Completers |
|
177 (86%) |
78 (79%) |
|
|
Early Discontinuation |
|
5 (2%) |
7 (7%) |
|
|
ITT |
|
182 (89%) |
85 (86%) |
|
|
Overdue for 24-month |
|
10 (5%) |
8 (8%) |
|
The sponsor also defined the following
populations for analysis:
·
All Randomized Subjects population:
all patients enrolled.
·
Intent-to-Treat (ITT) population:
all patients who were randomized in the study and had either a 24-month
follow-up evaluation or had been declared an “early discontinuation” (i.e., lost
to follow-up). Patients who were not yet due for follow-up or those who were
overdue for the 24-month evaluation were not included in the ITT group.
·
Completers population: patients who
were evaluated at 24 months regardless of whether the visit was within the
defined evaluation time window (22 months to 26 months)
·
Completers In-Window population:
patients who had the 24-month evaluation within the defined evaluation time
window (22 months to 26 months)
·
Safety population: all patients who
were randomized and received treatment.
The patients were categorized as “early
discontinuations” if they were non-compliant with the investigational protocol,
voluntarily withdrew from the study, refused to return for follow-up, or died.
In the Charité group, there were 5 patients who were early discontinuations: 2
patients who were non-compliant, 1 voluntary withdrawal, 1 refusal to return for
follow-up, and 1 death. For the BAK group, there were 7 patients who were early
discontinuations: 4 patients who were non-compliant, 2 voluntary withdrawals,
and 1 lost to follow-up (left the U.S. and unable to return). These early
discontinuations were infrequent and were more frequent in the BAK control group
(7% v. 2%).
Because the sponsor closed the database before
the end of the 24-month evaluation time window, there are some patients who have
reached the 24-month time point but are not outside the 24 month ± 2 month time
window. There are 10 (5%) Charité and 8 (8%) BAK patients in this “Not Yet
Overdue” category. These have been eliminated from the ITT population.
Thus, the ITT group (182 Charité patients and
85 BAK patients) consisted of All Randomized Subjects who either returned for
follow-up within the 24-month evaluation time window (158 Charité patients and
72 BAK patients), or outside the 24-month time window (19 Charité patients and 6
BAK patients), as well as those categorized as “early discontinuations” (5
Charité patients and 7 BAK patients).
There were 19 patients (13 patients, or 6%, in
the Charité group and 8 patients, or 6%, in the BAK group) who were “not yet
overdue” for the 24-month follow-up evaluation, i.e., they had reached the
24-month evaluation time point but were still within the 24-month evaluation
time window (±2 months).
Results
·
Primary Endpoint
OVERALL SUCCESS
Individual patient success was defined as a
patient with all of the following conditions:
·
Improvement >25% Oswestry at 24
months compared to baseline
·
No device failures requiring
revision, reoperation or removal
No pseudarthrosis (control group)
·
Absence of major complication,
defined as vessel injury, neurological damage, or nerve root injury
·
Maintenance or improvement in
neurological status at 24 months, with no permanent neurological deficits
compared to baseline
The overall success rates for the
Charité and the BAK groups were 63% and 53%,
respectively, for the ITT population (p<0.0001). The overall success rates for
the Completers and Completers In-Window populations were nearly identical.
|
Overall Success,
Table 19 |
|
|
Charité Artificial Disc |
BAK Cage |
p value |
|
N |
182 |
85 |
|
|
ITT population |
114 (63%) |
45 (53%) |
<0.0001 |
|
|
|
|
|
|
N |
177 |
78 |
|
|
Completers |
115 (65%) |
46 (59%) |
0.0005 |
|
|
|
|
|
|
N |
158 |
72 |
|
|
Completers In-Window |
101 (64%) |
42 (58%) |
0.0015 |
|
Success
Rates, Table 20 |
|
|
Charité Artificial Disc |
BAK Cage |
p value |
|
N |
182 |
85 |
|
|
Oswestry success (>25% improvement) |
127 (70%) |
49 (58%) |
0.0540 |
|
Device failure success (none) |
174 (96%) |
77 (91%) |
0.1632 |
|
Major complication success (none) |
180 (99%) |
84 (99%) |
1.0000 |
|
Neurological deterioration success (none) |
160 (88%) |
74 (87%) |
0.8437 |
The sponsor performed sensitivity analyses for
the primary efficacy success endpoints
(Section 8.4.2.7, Statistics, p.27; Section 8.4.4, Effectiveness, p.39).
These included analyses of the ITT subjects with non-completers considered to be
failures; ITT subjects with any 24-month follow-up; ITT subjects with 24-month
follow-up within the 24-month time window; “last observation carried forward,”
or LOCF, for All Randomized Subjects; LOCF for ITT; LOCF with discontinuations
as failures; overall LOCF for overdue patient. LOCF was performed for All
Randomized Patients and All Randomized Patients with discontinuations considered
failures. For all of these analyses, the overall success rate for the Charité
Artificial Disc Group ranged from 63% to 68%, and the overall success rate for
the BAK Group ranged from 48% to 54% (see Tables 21a and 21b). An analysis was
also performed removing the neurological component of success, and again showed
a higher proportion of success for non-completers, slightly higher in the
Charité Artificial Disc Group.
The overall success rate for the Charité
Artificial Disc Group is sustained over time. A repeated measures model
demonstrated that the success rates for the ITT groups at 6 months, 12 months
and 24 months were 69.2%, 67.6%, and 64.2% for the Charité Group, and 47.8%,
58.8%, and 54.7% for the BAK Group (see Table 22). An analysis of the time to
sustained response, i.e., the first time when success for the BAK Group was
observed and continued through 24 months, was performed. For the Charité Group,
the times to first response at 6 months, 12 months and 24 months were 44%, 51%,
and 63%, and for the BAK Group they were 35%, 41%, and 53%.
Subgroup and covariate analyses were performed
(see Table 23.1). The following factors were found to be not significant at the
0.15 level: age, baseline Oswestry score, gender, operative level, use of
hormone replacement therapy, and use of pain medication. The following factors
were found to be associated with the outcome: body mass index (but no treatment
interaction); current activity (better in active patients in the Charité group,
and better in inactive patients in the BAK group); osteopenia (Charité performed
better than BAK; however, this involved only 15 total patients); and study site.
There were no significant differences in the
success rates for the individual components of the Overall Success definition at
24 months:
OSWESTRY SUCCESS
·
Improvement >25% Oswestry at 24
months compared to baseline
The
Oswestry success rates for the
Charité and the BAK groups were 70% and 58%,
respectively, for the ITT population (p=0.0540).
|
Oswestry
Success
Defined as >25% Improvement, Table 20.1a |
|
|
Charité Artificial Disc |
BAK Cage |
p value |
|
N |
182 |
85 |
|
|
ITT population |
127 (70%) |
49 (58%) |
0.0540 |
|
|
|
|
|
|
N |
177 |
78 |
|
|
Completers |
127 (72%) |
49 (63%) |
0.1860 |
|
|
|
|
|
|
N |
158 |
72 |
|
|
Completers In-Window |
112 (71%) |
46 (64%) |
0.2886 |
DEVICE FAILURES SUCCESS
·
No device failures requiring
revision, reoperation or removal
·
No pseudarthrosis (BAK Control
Group)
The Device
Failure success rates for the
Charité and the BAK groups were 96% and 91%,
respectively, for the ITT population (p=0.0490).
|
Device Failure
Success
Defined No Device Failure, Table 20.1a |
|
|
Charité Artificial Disc |
BAK Cage |
p value |
|
N |
182 |
85 |
|
|
ITT population:
Failures |
8 (4%) |
8 (9%) |
0.1632 |
|
ITT population:
Successes |
174 (96%) |
77 (91%) |
|
|
|
|
|
|
N |
177 |
78 |
|
|
Completers |
170 (96%) |
71 (91%) |
0.1350 |
|
|
|
|
|
|
N |
158 |
72 |
|
|
Completers In-Window |
153 (97%) |
66 (92%) |
0.1030 |
MAJOR COMPLICATIONS SUCCESS
·
Absence of major complication,
defined as vessel injury, neurological damage, or nerve root injury
The Major
Complications success rates for the
Charité and the BAK groups were 99% and 99%,
respectively, for the ITT population (p=1.000).
|
Complications
Success
Defined as No Major Complication, Table
20.1a |
|
|
Charité Artificial Disc |
BAK Cage |
p value |
|
N |
182 |
85 |
|
|
ITT population |
180 (99%) |
84 (99%) |
1.0000 |
|
|
|
|
|
|
N |
177 |
78 |
|
|
Completers |
175 (99%) |
77 (99%) |
1.0000 |
|
|
|
|
|
|
N |
158 |
72 |
|
|
Completers In-Window |
157 (99%) |
71 (99%) |
0.5290 |
NEUROLOGICAL SUCCESS
·
Maintenance or improvement in
neurological status at 24 months, with no permanent neurological deficits
compared to baseline
The
Neurological success rates for the
Charité and the BAK groups were 88% and 87%,
respectively, for the ITT population (p=0.8437).
The sponsor performed subgroup and covariate
analyses. The following were found to be not significant: age (≤45 years v. >45
years), baseline Oswestry, gender, operative level, use of hormone replacement
therapy, and use of pain medication. The following were found to be associated
with the outcome as either a main effect or in the interaction term: body mass
index, current activity level, osteopenia, and study site.
|
Neurological
Success
Defined As No Deterioration of
Neurological Status, Tables 20.1a and 29.1 |
|
|
Charité Artificial Disc |
BAK Cage |
p value |
|
N |
182 |
85 |
|
|
ITT population |
160 (88%) |
74 (87%) |
0.8437 |
|
|
|
|
|
|
N |
177 |
78 |
|
|
Completers |
160 (90%) |
74 (95%) |
0.3239 |
|
|
|
|
|
|
N |
158 |
72 |
|
|
Completers In-Window |
144 (91%) |
68 (94%) |
0.4422 |
·
Secondary Endpoints
OSWESTRY DISABILITY INDEX
The mean Oswestry score by study population, by
follow-up time, by treatment group, and the changes from baseline were
analyzed.
Both the Charité and the BAK group patients
experienced significant improvements in their ODI from baseline at the 6-week,
3-month, 6-month, 12-month, and 24-month evaluation timepoints. The Charité
group patients had a significantly greater change in the ODI at the 6-week,
3-month and 6-month time points, although the differences were not significant
at the later timepoints.
|
Oswestry Disability Index
ITT Population, Table 27.1 |
|
|
Baseline |
6 wk |
3 mo |
6 mo |
12 mo |
24 mo |
|
Charité, n |
182 |
174 |
168 |
170 |
169 |
177 |
|
ODI |
49.8 |
37.4 |
29.6 |
27.1 |
25.9 |
25.8 |
|
Change* |
|
-22.9 |
-39.5 |
-45.5 |
-48.3 |
48.9 |
|
From baseline, p |
|
<0.0001 |
<0.0001 |
<0.0001 |
<0.0001 |
<0.0001 |
|
|
|
BAK, n |
85 |
78 |
81 |
76 |
72 |
79 |
|
ODI |
51.7 |
43.7 |
36.7 |
34.8 |
30.9 |
30.1 |
|
Change* |
|
-12.8 |
-26.7 |
-32.4 |
-39.9 |
-43.4 |
|
From baseline, p |
|
<0.0001 |
<0.0001 |
<0.0001 |
<0.0001 |
<0.0001 |
|
Between groups, p |
|
0.0485 |
0.0087 |
0.0126 |
0.1197 |
0.3407 |
*a negative change indicates an improvement in
the ODI.
The number of patients who achieved greater than
25% improvement in the ODI from baseline as also greater in the Charité group
patients at the 6-week, 3-month and 6-month time points, but were not
significantly different at the later timepoints.
|
Improvement in Oswestry Scores from
Baseline
(≥25%
Improvement), Table 26.1 |
|
|
6 wk |
3 mo |
6 mo |
12 mo |
24 mo |
|
Charité, n |
174 |
168 |
170 |
169 |
177 |
|
Improved |
80 (46%) |
107 (64%) |
121 (71%) |
120 (71%) |
128 (72%) |
|
|
|
|
|
|
|
|
Charité, n |
78 |
81 |
76 |
72 |
79 |
|
Improved |
24 (31%) |
37 (46%) |
41 (54%) |
47 (64%) |
49 (63%) |
|
|
|
|
|
|
|
|
Between groups, p |
0.0269 |
0.0091 |
0.0130 |
0.3637 |
0.1860 |
NEUROLOGICAL STATUS
|
Neurological Status
ITT Analysis, Table 29.1 |
|
|
Charité Group |
BAK Group |
|
N |
182 |
85 |
|
No change |
131 (77%) |
58 (76%) |
|
Significantly improved |
5 (3%) |
5 (7%) |
|
Slightly improved |
27 (16%) |
7 (9%) |
|
Slightly deteriorated |
7 (4%) |
3 (4%) |
|
Significantly deteriorated |
1 (1%) |
3 (4%) |
|
Mixed response |
0 |
0 |
|
Total |
171 |
76 |
|
Missing |
11 |
9 |
PAIN VISUAL ANALOG SCALE
(Tables 30.1-31.2)
The sponsor provided the Pain VAS scores for
both groups at each follow-up time point. The mean change from baseline
(measured at 6 weeks) varied from -35.9 to -41.1 for the Charité group and from
-28.6 to -35.1 in the BAK group. There were 128 (74%) Charité patients who were
Pain VAS successes (≥20mm improvement from baseline) compared to 49 (62%) BAK
patients (p=0.0759).
|
Pain VAS
ITT Analysis, Table 31.1 |
|
|
Charité Group |
BAK Group |
|
N |
182 |
85 |
|
Significant improvement (≥20mm)* |
128 (74%) |
49 (62%) |
|
Some Improvement |
22 (13%) |
11 (14%) |
|
No change (-3mm to +3mm) |
3 (2%) |
6 (8%) |
|
Deterioration (≥3mm) |
21 (12%) |
13 (16%) |
|
Total |
174 |
79 |
|
Missing |
8 |
6 |
* Success = ≥20mm improvement
QUALITY OF LIFE SF-36
(Tables 32.1-33.2)
For the component SF-36 scores, 99 (73%) Charité
patients and 41 (66%) BAK patients had a 15% or greater improvement in the
Physical Composite Score (PCS) at 24 months, and 68 (50%) and 34 (55%) patients
had a 15% improvement, for the Mental Composite Score (MCS), respectively.
These were not significantly different (p=0.3475 and 0.4959, respectively).
DISC HEIGHT
In the Charité group, there were no patients who
had a decrease in disc height greater than 3mm at 24 months. There were 3
patients in the BAK group who lost more than 3mm in disc height (4%).
RANGE OF MOTION
(Tables 35.1)
The vertebral range of motion measured on the
lateral flexion and extension views using the Cobb method at the operated level
was measured at 3, 6, 12, and 24 months. At all intervals, the Charité
Artificial Disc demonstrated near-physiologic ROM (mean). The mean ROM was 4.9,
6.0, 7.0 and 7.4 degrees, respectively.
|
Vertebral Range of Motion
Table 35.1 |
|
|
3 months |
6 months |
12 months |
24 months |
|
N |
133 |
163 |
161 |
175 |
|
Mean (degrees) |
4.9 |
6.0 |
7.0 |
7.4 |
|
Standard deviation (degrees) |
3.89 |
4.56 |
4.92 |
5.24 |
|
Median (degrees) |
4.4 |
5.2 |
6.3 |
6.9 |
|
Range, min-max (degrees) |
0-19 |
0-20 |
0-20 |
0-22 |
Normal segmental range of motion is defined as
up to 10 degrees of motion measured on lateral flexion-extension films.
Normal lumbar segmental range of motion has been
documented in the literature. In Pearcy and Shepherd (Pearcy M, Portek I,
Shepherd J: Three-dimensional x-ray analysis of normal movement in the lumbar
spine. Spine, 9(3): 294-297, 1984), the radiographically measured range
of motion of the L4L5 motion segment was 13 degrees of
flexion and 2 degrees of extension, with a 16 degree flexion-extension arc (s.d.
= 4 degrees). At the L5S1 motion segment, the range of
motion was 9 degrees of flexion and 5 degrees of extension, with a 14 degree
flexion-extension arc (s.d. = 5 degrees). Therefore, the mean range of motion
found in this investigation (4.9 at 3 months up to 7.4 degrees at 24 months) was
within the normal range of motion, and the patients at the extreme ROM (up to a
mean of 22 degrees) are still within 2 standard deviations of the mean. Thus,
the Charité patients did achieve near-normal segmental motion at the operated
segments.
The design characteristics of the device allow
for 24 degrees of flexion, 32 degrees of extension, 32 degrees of lateral
bending, and 360 degrees of axial rotation. Thus, the clinically demonstrated
motion is within the design parameters for the device.
The lateral bending and axial rotational range
of motion were not reported for this investigation. The normal range of motion
reported in Pearcy and Tibrewal (Pearcy MJ and Tibrewal SB: Axial rotation and
lateral bending in the normal lumbar spine measured by three-dimensional
radiography. Spine, 9(6): 582-587, 1984) at the L4L5
motion segment was found to be 3 degrees of axial rotation (range 1-5 degrees),
and 6 degrees of lateral bending (range 1-9 degrees). For the L5S1
motion segment, the normal range of motion was 2 degrees of axial rotation
(range 0-3 degrees), and 3 degrees of lateral bending (range 1-6 degrees).
Because these motions were not measured in this IDE study, no conclusions about
the device’s ability to restore normal lateral bending and rotational ranges of
motion can be made.
DEVICE MIGRATION
(Tables 35.1)
There were no device migrations reported for the
BAK group. At 3, 6, 12, and 24 months, there were 2 (1%), 1 (1%), 2 (1%), and 3
(2%) migrations >3mm in the Charité group.
PSEUDARTHROSIS AND RADIOLUCENCIES
In the BAK group, there were 2 (3 %) patients with a pseudarthrosis at 6 months,
2 (3%) at 12 months, and 4 (5%) at 24 months (Table 35.1). In the Charité
group, a radiolucency was identified in 1 (1%) patient at 12 months and 2 (1%)
patients at 24 months; longitudinal ossifications were identified in 1 (1%), 3
(2%), 6 (4%), and 11 (6%) patients at 6 weeks, 6 months, 12 months and 24
months, respectively (Tables 35.1 and 36.1).
WORK STATUS
(Table 37.1)
For both groups, there were decreases in the
number of patients on short-term disability compared to baseline. At baseline,
there were 15 (8%) patients in the Charité group compared to 8 (6%) patients in
the BAK group on short-term disability. At 12 months, there were 1 (1%) and 1
(1%) patient, respectively, and at 24 months there were 1 (1%) and 0 patients,
respectively, on short-term disability.
SUBJECT SATISFACTION
(Table 38.1)
Subject satisfaction was higher for the Charité
group patients than the BAK patients. At 24 months, the difference was
significant (p=0.0092).
|
Patient Satisfaction |
|
|
12 months |
24 months |
|
|
Charité Group |
BAK Group |
Charité Group |
BAK Group |
|
N |
182 |
85 |
182 |
85 |
|
Satisfied |
118 (72%) |
42 (59%) |
129 (73%) |
43 (55%) |
|
Somewhat satisfied |
33 (20%) |
16 (23%) |
27 (15%) |
20 (26% |
|
Somewhat dissatisfied |
8 (5%) |
6 (8%) |
17 (10%) |
5 (6%) |
|
Dissatisfied |
6 (4%) |
7 (10%) |
4 (2%) |
10 (13%) |
|
|
|
|
|
|
|
Same treatment? |
|
|
|
|
|
Definitely YES |
123 (74%) |
42 (59%) |
122 (69%) |
40 (52%) |
|
Probably YES |
22 (13%) |
12 (17%) |
23 (13%) |
10 (13%) |
|
Not sure |
14 (8%) |
9 (13%) |
21 (12%) |
12 (16%) |
|
Probably NOT |
2 (1%) |
3 (4%) |
1 (1%) |
5 (6%) |
|
Definitely NOT |
6 (4%) |
5 (7%) |
10 (6%) |
10 (13%) |
·
Adverse Events
The sponsor collected adverse event information on all randomized patients
(“Safety Population”), and categorized them as follows: typical or unusual
(Table 40.1-40.2); severe or life-threatening (Table 41.1-41.2); device-related
or not device-related (Table 42.1-42.2); severe and device-related (Table
43.1-43.2); occurring within 2 days of surgery (Table 44.1-44.2); and by date of
onset categories (Table 45.1-45.2).
|
Adverse Events
Table 39 |
|
|
Charité Group |
BAK Group |
|
|
Patients |
% |
Patients |
% |
|
Patients enrolled |
205 |
|
99 |
|
|
Patients with an adverse event |
156 |
76.1 |
77 |
77.8 |
|
Pain, back or lower extremity, total |
107 |
52.5 |
52 |
52.5 |
|
Device-related |
10 |
4.9 |
2 |
2.0 |
|
Not Device-related |
97 |
47.3 |
50 |
50.5 |
|
Other |
46 |
22.4 |
26 |
26.3 |
|
Neurological, total |
34 |
16.6 |
17 |
17.2 |
|
Device-related |
3 |
1.5 |
0 |
0 |
|
Not Device-related |
31 |
15.1 |
17 |
17.2 |
|
Pain (other), total |
27 |
13.2 |
9 |
9.1 |
|
Device-related |
0 |
0 |
0 |
0 |
|
Not Device-related |
27 |
13.2 |
9 |
9.1 |
|
Infection, total |
25 |
12.2 |
6 |
6.1 |
|
Device-related |
1 |
1 |
0 |
0 |
|
Not Device-related |
14 |
11.7 |
6 |
6.1 |
|
Approach problems (abdominal) |
18 |
8.8 |
8 |
8.1 |
|
Fusion treatment related |
0 |
0 |
26 |
26.3 |
|
Device-related |
0 |
0 |
1 |
1.0 |
|
Not Device-related |
0 |
0 |
25 |
25.3 |
|
DDD progression, natural history, total |
6 |
2.9 |
4 |
4.0 |
|
Device-related |
0 |
0 |
1 |
1.0 |
|
Not Device-related |
6 |
2.9 |
3 |
3.0 |
|
Prosthesis related, total |
8 |
3.9 |
1 |
10 |
|
Device-related |
2 |
1.0 |
0 |
0 |
|
Not Device-related |
6 |
2.9 |
1 |
1.0 |
|
Additional surgery, Index level |
10 |
4.9 |
8 |
8.1 |
|
Device-related |
5 |
2.4 |
1 |
1.0 |
|
Not Device-related |
4 |
2.0 |
8 |
8.1 |
|
Additional surgery, other than index level |
3 |
1.5 |
3 |
3.0 |
|
Intraoperative complications |
2 |
1.0 |
3 |
3.0 |
|
Abnormal bone formation |
|
;)
;)
