Brief Report
Restore Orthobiologic Soft Tissue Implant for rotator cuff repair
Zhi-ling Zhang
June 2009
Evidence Based Healthcare Advisory Group Research and Development ACC
Important Note This brief report summarises information on the effectiveness and safety of Restore Orthobiologic Soft Tissue Implant for rotator cuff repair. It is not intended to replace clinical judgement, or be used as a clinical protocol. A reasonable attempt has been made to find and review papers relevant to the focus of this report. It does not claim to be exhaustive. This document has been prepared by staff of ACC, Evidence Based Healthcare Advisory Group. The content does not necessarily represent the official view of ACC or represent ACC policy.
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Acknowledgements The draft of this report was circulated to several internal and external experts for peer review, including: •
Dr Craig Ball, Shoulder and Elbow Specialist, Ascot Hospital, Auckland
•
Dr Alex Malone, Orthopaedic Surgeon (upper limb surgery), Leinster Orthopaedic Centre, Christchurch
•
Dr Kevin Morris, Director of Clinical Services, ACC, Wellington
•
Dr Alastair Wilson, Corporate Medical Advisor, ACC, Wellington
•
Dr Graham Corbett, Branch Medical Advisor, ACC, Whangarei
•
Dr Peter Larking, Research Services, ACC, Wellington.
The author is grateful for their comments on the draft report. The conclusions in this final report are the views expressed by the author.
The author thanks Helen Brodie and Beth Tillier of ACC Library Services for their kind support in obtaining related materials used in this report.
Some product information was kindly provided by Mr. Chris Iggo, Manager, Market Development, DePuy Trauma and Extremities, Asia Pacific. Auckland, New Zealand.
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Background Rotator cuff tears are very common shoulder conditions, strongly associated with increasing age1. Management of rotator cuff tears includes non-surgical treatments e.g anti-inflammatory drug treatment and rehabilitation; and surgical treatments e.g. rotator cuff repair, subacromial decompression and tendon transfers 2 ,3. With a relatively high failure rate (ranged from 20% to 65%), surgical repair of large or massive rotator cuff tears remains a significant challenge in clinical practice
2 ,4
. In the last decades, new techniques including bio-absorbable graft
materials have been tried to improve healing rate and other clinical outcomes of the rotator cuff repair.
In 2002, ACC was asked to fund Restore Orthobiologic Soft Tissue Implant (Restore implant) for rotator cuff repair. The Evidence Based Healthcare Group conducted a brief assessment on the implant and found that: •
There was no published clinical study at that time. Therefore, the clinical effectiveness of the implant could not be assessed5.
•
Seven adverse events in relation to Restore implant were found in the FDA’s Manufacturer and User Facility Device Experience Database (MAUDE). These events were reported in 2001 and the first two quarters of 2002. The risk of adverse events could not be quantified due to the lack of information on the number of the implant used. These adverse events exhibited a similar pattern of “infection-like symptoms” including swelling, redness, drainage and pain or fever after surgery. However, no evidence of bacterial infection was found from laboratory tests in these cases5.
•
Based on the brief assessment, a committee recommended ACC decline the funding request.
In the last two years, ACC has been asked by some healthcare providers to fund this implant for rotator cuff repairs. This brief report aims to summarise current available clinical information and to provide updated evidence for revising purchasing decision.
4
Product information According to the notification submitted to FDA by DePuy Orthopaedics Inc. (Indiana, USA), the Restore Orthobiologic Soft Tissue Implant is a round device, manufactured from 10 layers of Small Intestine Submucosa (SIS). SIS is a biomaterial derived from the porcine small intestine and is composed predominately of collagen (more than 90%), a small amount of carbohydrate and water6 ,7. The implant is intended for use in general surgical procedures for reinforcement of soft tissue where weakness exists. It is intended to act as a resorbable scaffold that initially has sufficient mechanical strength to assist with soft tissue repair, but then resorbs and is replaced by the patient’s own tissue 7.
This implant was approved for marketing in the USA by FDA under the category of 510 (k) in 1998 7. A 510 (k) is a pre-market submission made to the FDA to demonstrate that the device to be marketed is “at least as safe and effective, that is, substantially equivalent, to a legally marketed devices that are not subject to PMA” (Premarket Approval) 8. In terms of effective and safety, the implant was considered as substantially equivalent to the following surgical meshes and wound dressings: •
Organogenesis Graft Patch
•
Sentron SIS Hernia Repair Device
•
Bio-Vascular Supple Peri-guard
•
Cook Biotech Inc. SIS Surgical Mesh
•
Cook Biotech Inc. SIS Wound Dressing
Since this product was considered in the category of 510 (k), no clinical trial was required to demonstrate its effectiveness and safety by FDA.
The FDA also approved an expended intended use of the implant for reinforcement of soft tissues, which are repaired by suture or suture anchors during rotator cuff repair surgery in 2003, and for reinforcement of soft tissue repaired by sutures or suture anchors during other tendon repair surgeries, including the reinforcement of patellar, Achilles, biceps and quadriceps7.
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The first operation using this implant for rotator cuff repair was carried out in Stanford Hospital, California in 19999.
Information Searching We used OVID to search reports on the product, from a range of databases including MEDLINE, MEDLINE Daily Update, EMBASE, CDSR, ACP Journal Club, DARE, CCTR, CLCMR, CLHTA and CLEED. These databases were searched for to April 2009. The search strategy is presented in Appendix 1.
The Google was used to search for related information using the terms of “Restore Orthobiologic Soft Tissue Implant”, “Restore implant” and “Restore patch”. The 510 (k) Premarket Notification Database7 and the Manufacturer and User Facility Device Experience Database (MAUDE) in FDA website 10 were also searched. Some authors were contacted for more detailed information about their reports. DePuy Trauma and Extremities, Asia Pacific, Johnson & Johnson Medical Pty Limited in Auckland, New Zealand was also contacted for information of clinical studies on Restore implant. The company provided some reports from animal studies in relation to the product.
Methods of the review The included studies were appraised by the author for this review. The quality of each study was determined by using the Scottish Intercollegiate Guidelines Network (SIGN) grading system 11 (Appendix 2): Quality assessment: The quality of the studies was assessed by analysing the information including the definition of study population and treatment, criteria of inclusion and exclusion, methods of randomisation, the use of control group, baseline measurements of the study subjects in different study groups, blinding, sample size, outcome measurements, period of follow-up and potential bias in the studies. A table (Appendix 4) was used to summarise the characteristics of study subjects, treatment, outcomes and the level of evidence determined.
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Results Clinical effectiveness Four published clinical studies12-15 that reported effectiveness of Restore implant for rotator cuff repair were found. Iannotti reported a randomised controlled study12 which compared clinical outcomes in patents who received open surgical rotator cuff repair with or without the Restore implant. Thirty two patients with large to massive chronic tears of the supraspinatus and infraspinatus tendons were enrolled in the study; thirty patients completed one year follow up after the surgery. As assessed by magnetic resonance imaging (MRI) examination, healing of the rotator cuff was found in 4 of 15 patients who were treated by open surgical repair with Restore implant augmentation, and in 9 of 15 patients who were treated by open surgery only. After adjustment for the effect of tear size on the rate of healing, repairs without Restore implant were found to be 7% more likely to heal than with the implant. This result is not statistically significant (odd ratio = 1.07; p = 0.07). Shoulder function, pain, and patients’ satisfaction were assessed by PENN score (The University of Pennsylvania Shoulder Scale) in this study. In all score measurements, patients who were treated with surgical repair without Restore implant had better scores than those treated with the implant. However, the differences between the two groups were not statistically significant (p > 0.05) except for the difference of function score (p = 0.03). Based on this small study, the authors concluded that the use of Restore implant to augment rotator cuff repair did not improve the rate of tendonhealing or the clinical outcome.
Sclamberg reported a case series of 11 consecutive patients with large to massive rotator cuff tears
14
who were treated by open surgical repair with the Restore implant. All these patients
had extensive atrophy and retraction of their suprapinatus and infraspinatus. MRI examination at 6 month follow up showed that 10 of 11 patients had recurrence of large, retracted tears. Only one repair remained intact at 10 months after surgery. There was no statistically significant difference between pre-operative and post-operative shoulder scores measured by the American Shoulder and Elbow Surgeons Shoulder Score (ASES). Five patients had worse scores post-operatively. The authors concluded that the use of the implant “seems to be ineffective and does not improve clinical outcome” 14.
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Walton reported a case series of 15 patients (16 shoulders repaired) with large to massive rotator cuff tears who were treated by conventional surgical repair with the Restore implant in Australia
15
. These patients were originally enrolled to a randomised controlled trial which
was then abandoned due to safety concerns about inflammatory reactions (see adverse events reported by Malcarney16 in the following section). Sixteen patients who were treated by conventional surgical repair without Restore implant were used as a comparison group. The comparison group were also from the abandoned RCT and retrospectively matched with the intervention group for mean age, tear size and gender ratio. The results showed that patients who were treated with the Restore implant had a higher activity related pain score at 3 months (but similar from 6 months to 2 years post surgery) and less participation in sport. There was no statistically significant difference in patients’ overall satisfaction. Among the patients scanned by MRI at two years post surgery, tears recurred in 6 of 10 patients who were treated with the Restore implant and 7 of 12 patients who were treated without the implant. The authors concluded that the use of the implant provided “no recognisable benefit” when compared with the results from the comparison group 15.
Mozes reported a case series using the Restore implant to reinforce rotator cuff repairs on 9 selected patients 13. Seven of these patients had recurrences of massive rotator cuff tears after previous surgical repairs; two were long standing neglected rotator cuff tears in patients with weight bearing shoulders (bilateral below the knees amputation and incomplete paraplegia after anterior poliomyelitis). These patients were followed for 6 to 22 months after surgical repair with the Restore implant. “Excellent and good results”13 were observed in 8 cases. One patient, who had previously received repairs twice, had a third failure. In the eight successful cases, “an almost normal pain-free active range of movement was observed three months after surgery”13. The authors concluded “use of the Restore soft tissue implant could possibly be utilised to strengthen the repair, as well as the inside ingrowth of the tendon, leading to a successful repair of the rotator cuff”13. This case series was reported as an abstract. There is significant lack of some clinical information e.g. the outcome assessment. We are unable to get more detailed information of this case series from the authors or the related professional organisation in Israel.
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Safety Malcarney16 reported 4 cases of early inflammatory reaction after rotator cuff repair with the Restore implant in Australia. These 4 cases (16%) were among 25 patients who underwent conventional rotator cuff repair with the Restore implant by one surgeon during a 6 month period in Sydney.
These four patients developed an overt, inflammatory reaction at a mean of 13 days after surgery. The reaction was characterised by an erythematous surgical wound with subcutaneous fluctuance which was similar to early postoperative infection. Two of the 4 patients had drainage from their wound. All 4 patients were taken back to surgery for irrigation and debridement of superficial and deep tissues including the rotator cuff. The implant could not be identified as a whole; however, a large amount of yellow mucinous tissue was found during the surgical irrigation and debridement. The tissue formed a patchy veil over the remaining rotator cuff where the implant had been sutured 16. Laboratory results did not indicate microbiological infection. Histopathological findings indicated an acute inflammatory reaction to the implant. However, there were no eosinophils to suggest an allergy or giant cells to suggest a foreign body reaction.
Eighteen months after the surgical irrigation and debridement, three of four patients were evaluated. All three patients reported mild stiffness, and demonstrated moderate to severe rotator cuff weakness. The patients also reported mild to moderate pain. Due to these complications, a randomised controlled trial to compare rotator cuff repair with or without the Restore implant was abandoned as previously described.
Iannotti also reported complications in 3 of 16 patients who were treated by surgical repair with Restore implant in the randomised controlled trial12. One patient developed erythema and spontaneous drainage from the wound 3 weeks after the surgery. This patient was treated with immediate open irrigation and debridement. There was no bacterial growth on culture of any specimens taken during the procedure prior to the administration of antibiotics. Pathological examination of the tissue demonstrated acute inflammation. In another patient, swelling of the shoulder and increasing pain developed 6 weeks after the surgery. The subaromial space was aspirated and the white blood cell count in the aspirate was 16,000/mm3. Oral antibiotics were administered, but the therapy was discontinued seven days later when the final culture results
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were revealed to be negative. One year post surgery, MRI examination showed a complete two-tendon tear equal in size to the tear seen on the preoperative MRI scan. In the third patient, erythema and increased skin temperature around the wound developed at four weeks after the surgery patient. The symptoms resolved without any treatment. MRI scan showed a partially healed repair one year after surgery.
Adverse events after using the Restore implant for rotator cuff repair have also been reported in some conference presentations. For example, Dr Gorman reported “an immunologic reaction in 7 (22%) of 32 patients who had undergone a rotator cuff repair in which the Restore patch had been used for augmentation” at the Mid American Orthopaedic Association Annual Meeting held in Florida in April 2005
17 ,18
. We are unable to get more detailed
information about the report from the author. Prof. Zheng at University of Western Australia also reported that “local clinical experience with Restore SIS for tendon repair demonstrated prominent noninfectious swelling and severe pain at the site of implantation (unpublished data)”19. Adverse events related to medical devices listed in the MAUDE Device database10 was search in 2002; there were seven adverse events involving “Restore Soft Tissue Implant” reported in 2001 and the first two quarters of 2002. These adverse events are listed in Appendix 3.
An update search on the database was carried out in April 2009. Another 31 adverse events in relation to the Restore implant were found. Not all these records have detailed event descriptions which can be reviewed to determine the types of surgical procedure used with the Restore implant. Among them, nine adverse events were clearly described including redness, pain and swelling in the implantation site after rotator cuff repairs. Laboratory tests were negative for bacteria in these cases. The clinical patterns of these adverse events in the MAUDE database appear to be similar to those reported in the individual studies previously described12 ,16. However, the incidence of the adverse events cannot be quantified from this source due to the lack of information on numbers of implants used and lack of detailed clinical information reported in some events.
Characteristics of these included clinical studies are presented in Appendix 4.
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Discussion Methodological quality Compared with the previous review (2002) in which no clinical study was found, some clinical studies have been identified. However, numbers of clinical studies using the Restore implant for rotator cuff repair are still limited. Only five published studies (including an abstract) with relevant clinical outcomes were found. A reasonable attempt was made to obtain detailed information and data of other studies in the gray literature, but without success.
Randomised controlled studies are the gold standard for investigation of effectiveness of clinical interventions. Only one randomised control trial12 was found in this updated assessment. The study compared clinical outcomes of open surgical repair with or without the Restore implant and therefore is appropriately designed to investigate whether the Restore implant adds any clinical benefit. However, the sample size in this study appears to be very small. Even though all measurements in the control group were better than the intervention group; the differences between the groups were not statistically significant apart from the median function score. Outcome assessment was not blinded, and the intention to treat principle was not used in the data analysis.
Clinical outcomes of patients treated by conventional rotator cuff repair were compared with those treated by the surgical repair with Restore implant in a case series by Walton
15
. In
addition to the small sample size, this study may also be subject to selection bias since the comparison group were retrospectively matched. The case series reported by Sclamberg 14 and Mozes 13 also had a small sample sizes (11 and 7 patients respectively). The follow up of the case series reported by Sclamberg was also relatively short (6 to 10 months).
Theoretically, more randomised control trials are needed in the future. However, it is difficult to predict whether the new studies will take place since there are safety concerns with the implant. A randomised controlled trial was abandoned due to safety concerns in Australia ,16
. 11
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Effectiveness and safety The only available randomised controlled study12 showed that there was no statistical differences in outcomes between open surgical repair with or without Restore implant. These results indicate that the Restore implant may not provide clinical benefit for rotator cuff repair. It may be argued that the statistical insignificance is due to a small sample size. However, most measurements in this study showed that the patients treated by surgical repair without the Restore implant had better results than those treated with the implant. Increasing the sample size is likely to change the statistical significance rather than the direction of the results.
Compared with a retrospectively matched comparison group, the case series reported by Walton15 ,16 also showed that outcomes of patients treated with the Restore implant are similar to or worse than those treated without the implant. Patients treated with the implant had significantly higher activity related pain scores than those without the implant at 3 months after the surgery. In the case series reported by Sclamberg14, retear occurred in ten of the eleven patients treated by surgical repair with the Restore implant 6 to 10 months after the surgery. Five of the eleven patients had worse shoulder scores after surgery. These results do not suggest that the surgical repair with the implant in is an effective treatment. The case series reported by Mozes13 is the only study that suggests positive outcomes from using the Restore implant in surgical repair. Eight of nine patients who received the treatment had “excellent and good results”. Retear only occurred in one patient. It is difficult to discuss the results further since there is no comparison group and the study is only reported in abstract.
There is a similar pattern of adverse events reported in the studies by Iannotti, Malcarney and cases reported in the MAUDE database. The events occurred a few weeks after surgery, and were characterised by an erythematous, swelling and painful surgical wounds. Some of these cases needed surgical irrigation and debridement. Laboratory tests were negative for bacteria. Therefore post-surgical bacterial infection can be excluded. A study carried out in Australia19 found that Restore implant is not an acellular biomaterial, and contains porcine DNA. This material has “the capacity to cause variable inflammatory 12
response after implantation”19. This finding may explain the adverse reaction after rotator cuff repair with the implant.
It is interesting to note the percentages of patients who developed the adverse reactions in three studies were not very different: 16% in the study by Malcarney 16, 20% in the study by Iannotti and 22% in the study by Gorman
17
. These numbers were reported in three small
sample size studies, and surgery appears to had been carried out before 2005.
Conclusions •
The number of studies that can be used to assess the clinical effectiveness and safety of the Restore implant are limited. Only one randomised controlled trial and some case series are available. All these studies have different limitations in methodology.
•
The available studies do not show that the Restore implant provides additional clinical benefit for surgical rotator cuff repair.
•
Use of the implant is associated with a risk of developing non-infectious reactions in the implantation site.
•
Uncertainty of clinical benefit of the implant, risk of adverse reactions and an additional cost of the implant to rotator cuff repair need to be considered in related decision making.
References 1. Yamaguchi K, Ditsios K, Middleton WD, Hildebolt CF, Galatz LM, Teefey SA. The demographic and morphological features of rotator cuff disease. A comparison of asymptomatic and symptomatic shoulders. Journal of Bone & Joint Surgery - American Volume 2006;88(8):1699-1704. 2. Williams GR, Jr., Rockwood CA, Jr., Bigliani LU, Iannotti JP, Stanwood W. Rotator cuff tears: why do we repair them? Journal of Bone & Joint Surgery - American Volume 2004;86-A(12):2764-2776. 3. New Zealand Guideline Group. The diagnosis and management of soft tissue shoulder injuries and related disorders - best practice evidence-based guideline, 2004. 4. Coons DA, Alan Barber F. Tendon graft substitutes-rotator cuff patches. Sports Medicine & Arthroscopy Review 2006;14(3):185-190.
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5. Zhang ZL, Mai D. DePuy Restore Orthobiologic Soft Tissue Implant. Wellington, Accident Compensation Corporation 2002. 6. DePuy Orthopaedics Inc. Restore Orthobiologic Implant: For rotator cuff repair. Warsaw, Indiana, 2001. 7. FDA. 510(k) Premarket Notification Database: on http://www.accessdata.fda.gov, Accessed on 20 May 2009. 8. FDA. Premarket Notification 510(k). on http://www.fda.gov/CDRH/DEVADVICE/314.html. Accessed on 20 May 2009. 9. Samson K. Stanford goes to the farm for rotator cuff repair. Biomedical Instrumentation and Technology 1999;33(4):342-343. 10. FDA. MAUDE - Manufacturer and User Facility Device Experience. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/search.CFM, Accessed on 20 May 2009. 11. SIGN. Grading system for recommendations in evidence-based clinical guidelines--report of a review of the system for grading recommendations in SIGN guidelines: Scottish Intercollegiate Guidelines Network (SIGN), 2000. 12. Iannotti JP, Codsi MJ, Kwon YW, Derwin K, Ciccone J, Brems JJ. Porcine small intestine submucosa augmentation of surgical repair of chronic two-tendon rotator cuff tears: A randomized, controlled trial. Journal of Bone and Joint Surgery 2006;Series A 88(6):12381244. 13. Mozes G, Maman E, Parnes N. Repair of massive rotator cuff tears reinforced by Restore Orthobiologic Soft Tissue Implant. Preliminary study J Bone Joint Surg Br 2006 2006;88B:344-345. 14. Sclamberg SG, Tibone JE, Itamura JM, Kasraeian S. Six-month magnetic resonance imaging follow-up of large and massive rotator cuff repairs reinforced with porcine small intestinal submucosa. Journal of Shoulder & Elbow Surgery 2004;13(5):538-541. 15. Walton JR, Bowman NK, Khatib Y, Linklater J, Murrell GAC. Restore orthobiologic implant: not recommended for augmentation of rotator cuff repairs. Journal of Bone & Joint Surgery - American Volume 2007;89(4):786-791. 16. Malcarney HL, Bonar F, Murrell GAC. Early inflammatory reaction after rotator cuff repair with a porcine small intestine submucosal implant: a report of 4 cases.[see comment]. American Journal of Sports Medicine 2005;33(6):907-911. 17. Rubino LJ, 3rd, Miller MD. What's new in sports medicine. Journal of Bone & Joint Surgery - American Volume 2006;88(2):457-468. 18. Anonymous. Orthopaedic News, Spring 2006. on http://www.docftp.com/doc/123056; Accessed on 14 May 2009.
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19. Zheng MH, Chen J, Kirilak Y, Willers C, Xu J, Wood D. Porcine small intestine submucosa (SIS) is not an acellular collagenous matrix and contains porcine DNA: possible implications in human implantation. Journal of Biomedical Materials Research Part B, Applied Biomaterials 2005;73(1):61-67.
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Appendices
Appendix 1. Ovid search strategy 1 2 3. 4. 5 6 7 8 9 10 11 12 13
“Restore orthobiologic soft tissue implant”.af. (Restore adj5 implant).af. ( DePuy adj5 implant).af. (Restore adj5 patch).af. (DePuy adj5 Restore).af. or/1-5 Restore.mp. implant.mp. 7 and 8 porcine small intestine submucosa.af. “rotator cuff”.af. 10 and 11 6 or 9 or 12
16
Appendix 2. Level of evidence in the SIGN system
1++
High quality meta analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias
1+
Well conducted meta analyses, systematic reviews, or RCTs with a low risk of bias
1-
Meta analyses, systematic reviews, or RCTs with a high risk of bias
2++
High quality systematic reviews of case-control or cohort studies High quality case-control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal
2+
Well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal
2-
Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
3
Non-analytic studies, e.g. case reports, case series
4
Expert opinion
Appendix 3. Reported adverse events involving “Restore Soft Tissue Implant” in MAUDE database, 2001 and first two quarters of 2002
No
ID*
Date FDA
Device Age
Adverse event description
Additional manufacturer narrative
“TWO TO THREE DAYS FOLLOWING SURGERY; THE SURGEON NOTICED SWELLING; REDNESS AND FEVER AT THE IMPLANT SITE. A FEW DAYS LATER; HE NOTICED CLEAR FLUID WEEPING FROM THE SURGICAL SITE. CULTURES WERE NEGATIVE FOR AN INFECTION. EVENTUALLY; THE STAPLES FAILED AND THE SURGEON HAD TO GO BACK IN FOR A REVISION. NOTICED THAT THE IMPLANT WAS NOT PRESENT. IN FACT; HE COULDN'T EVEN FIND THE NON-ABSORBABLE SUTURES (MERCILIN) THAT WERE HOLDING THE RESTORE IMPLANT TO THE REPAIRED CUFF TENDON.”
“THE INVESTIGATION COULD NOT VERIFY THE REPORTED ADVERSE REACTION. THE PRODUCT REMAINS IMPLANTED. REVIEW OF THE DEVICE HISTORY RECORDS CONFIRMED THE PRODUCT WAS STERILIZED AND MET SPECIFICATION PRIOR TO DISTRIBUTION. THE INVESTIGATION COULD NOT VERIFY THE REPORTED PROBLEM OR IDENTIFY ANY PRODUCT CONTRIBUTION TO THE REPORTED EVENT. BASED ON THE COMPANY'S INVESTIGATION, THE NEED FOR CORRECTIVE ACTION IS NOT INDICATED. SHOULD ADDITIONAL INFORMATION BE RECEIVED, THE INVESTIGATION WILL BE REOPENED. MONITOR THROUGH TREND ANALYSIS. DEPUY CONSIDERS THE INVESTIGATION CLOSED AT THIS TIME.”
received 1
383170 03/21/2002
10 DAY
2
333306 05/18/2001
UNKNOWN “SURGEON USED THE RESTORE
3
336227 06/06/2001
12 DAY
“THE DR REPORTED THAT A PATIENT MAY BE HAVING IMMUNOLOGICAL REACTION PROBLEMS OR IS EXHIBITING INFECTION-LIKE SYMPTOMS FOLLOWING USE OF THIS IMPLANT. A FOLLOW-UP CALL TO PRODUCT MANAGER PROVIDED INFORMATION THAT THE PATIENT HAD TESTED POSITIVE FOR ANTIBODIES TO RAW PORK IN 1990 OR 1992 AND HAD NOT INFORMED THE SURGEON ABOUT THIS CONTRAINDICATION.”
“…PRODUCT CODE AS THE PRODUCT WAS NOT RETURNED. EVALUATION OF THE PRODUCT AS NOT POSSIBLE AS IT WAS NOT RETURNED. THE INVESTIGATION COULD NOT IDENTIFY THE EXACT CAUSE OF THE REPORTED SYSTEMS; HOWEVER, THE PT NOT INFORMING THE DOCTOR OF THE CONTRAINDICATION CONDITION MAY BE A CONTRIBUTING FACTOR. BASED ON CO'S INVESTIGATION, THE NEED FOR CORRECTIVE ACTION IS NOT INDICATED. SHOULD THE PRODUCT AND/OR ADDITIONAL INFORMATION BECAME AVAILABLE, THE INVESTIGATION WILL BE REOPENED. THIS WILL BE MONITORED THROUGH TREND ANALYSIS. DEPUY CONSIDERS THIS COMPLAINT CLOSED AT THIS TIME.”
4
348288 08/21/2001
1 MONTH
“THIS PATIENT COMPLAINED OF REDNESS AND SWELLING WITH CLEAR DISCHARGE ABOUT 4 WEEKS POSTOP. NO PRIOR INFECTION. DISCHARGE DID NOT CONTAIN INFECTION. PATIENT IS NOW RECOVERED AND TAKING THERAPY.”
“…USED AS PRODUCT NOT RETURNED. EVALUATION WAS NOT POSSIBLE AS THE PRODUCT REMAINS IMPLANTED. REVIEW OF THE DEVICE HISTORY RECORDS FOUND NO PROBLEMS. THE INVESTIGATION FOUND NO EVIDENCE OF PRODUCT CONTRIBUTION TO THE REPORTED PROBLEM. THE INVESTIGATION COULD NOT VERIFY OR IDENTIFY THE CAUSE OF THE REPORTED PORBLEM. BASED ON THE COMPANY'S INVESTIGATION, THE NEED FOR CORRECTIVE ACTION IS NOT INDICATED. MONITOR THROUGH TREND ANALYSIS. DEPUY CONSIDERS THIS COMPLAINT CLOSED AT THIS TIME.”
IMPLANT FOR A TORN ROTATOR CUFF. A FEW DAYS LATER THE PATIENT COMPLAINED OF PAIN AND REDNESS AROUND THE SHOULDER. SURGEON THOUGHT THAT THE PATIENT MIGHT HAVE AN INFECTION, BUT RULED OUT WHEN COULDN'T GROW CULURE. THE PATIENT'S SYSTEMIC WHITE COUNT WAS NORMAL, AND PROTEIN WAS NORMAL. CURRENTLY TREATING WITH STEROIDS AND ANTIBIOTICS. PATIENT DESCRIBED AS SOMEWHAT NONCOMPLIANT. PATIENT WAS SCOPED IN 2001.”
“…NO DEVICE RETURNED AS IT REMAINS IMPLANTED. EVALUATION WAS NOT POSSIBLE AS THE PRODUCT REMAINS IMPLANTED. THE LOT NUMBER REQUIRED TO REVIEW THE DEVICE HISTORY RECORDS WAS NOT PROVIDED. THE INVESTIGATION COULD NOT DRAW ANY CONCLUSIONS BASED ON THE LIMITED INFORMATION PROVIDED. SHOULD ADDITIONAL INFORMATION BECOME AVAILABLE, THE INVESTIGATION WILL BE REOPENED. COMPLAINTS WILL BE MONITORED THROUGH TREND ANALYSIS.”
5
348547 08/23/2001
28 DAY
“THIS PATIENT COMPLAINED OF REDNESS AND SWELLING WITH DISCHARGE ABOUT 4 WEEKS POST-OP. THE DISCHARGE DID NOT CONTAIN INFECTION. DR REFERRED THE PT TO ANOTHER DR WHO PERFORMED REVISION. HE REMOVED WHAT WAS LEFT OF IMPLANT AND REPAIRED CUFF TENDON.”
“…USED AS THE PRODUCT IS NOT BEING RETURNED. EVALUATION WAS NOT POSSIBLE AS THE PRODUCT WAS NOT RETURNED. REVIEW OF THE DEVICE HISTORY RECORDS FOUND NO PROBLEMS. THE INVESTIGATION FOUND NO EVIDENCE OF PRODUCT CONTRIBUTION TO THE REPORTED PROBLEM. THE INVESTIGATION COULD NOT VERIFY OR IDENTIFY THE CAUSE OF THE REPORTED PROBLEM. BASED ON THE COMPANY'S INVESTIGATION, THE NEED FOR CORRECTIVE ACTION IS NOT INDICATED. SHOULD THE PRODUCT AND/OR ADDITIONAL INFORMATION BE PROVIDED, THE INVESTIGATION WILL BE REOPENED. DEPUY CONSIDERS THIS COMPLAINT CLOSED AT THIS TIME.”
6
354897 10/09/2001
14 DAY
“THE PATIENT DEVELOPED REDNESS WITH A LOT OF FLUID MATERIAL AND SWELLING ONE WEEK POST-OP. THE DOCTOR BELIEVES THE PATIENT EITHER BECAME INFECTED OR REJECTED THE MATERIAL. THE PATIENT WAS REVISED TWO WEEKS AFTER IMPLANT DATE.”
“EVALUATION WAS NOT POSSIBLE AS THE PRODUCT WAS NOT RETURNED. REVIEW OF THE DEVICE HISTORY RECORDS AND COMPLAINT DATABASE FOUND NO ISSUES. THE INVESTIGATION COULD NOT VERIFY OR IDENTIFY ANY ROOT CAUSE OF THE REPORTED PROBLEM. BASED ON THE CO'S INVESTIGATION, THE NEED FOR CORRECTIVE ACTION IS NOT INDICATED. SHOULD ADDITIONAL INFORMATION BE PROVIDED, THE INVESTIGATION COULD BE REOPENED. MONITOR THROUGH TREND ANALYSIS. DEPUY CONSIDERS THIS COMPLAINT CLOSED AT THIS TIME.”
7
354900 10/09/2001
14 DAY
“THE PATIENT DEVELOPED DRAINAGE FROM THE INCISION AT 1 TO 2 WEEKS POST-OP. THE FAMILY DOCTOR MAY HAVE OPENED (TO DRAIN INCISION) PRIOR TO REVISION. THE PATIENT IS A DIABETIC.”
“EVALUATION WAS NOT POSSIBLE AS THE PRODUCT WAS NOT RETURNED. REVIEW OF THE DEVICE HISTORY RECORDS AND COMPLAINT DATABASE FOUND NO ISSUES. THE INVESTIGATION COULD NOT VERIFY OR IDENTIFY ANY ROOT CAUSE OF THE REPORTED PROBLEM. BASED ON THE CO'S INVESTIGATION, THE NEED FOR CORRECTIVE ACTION IS NOT INDICATED. SHOULD ADDITIONAL INFORMATION BE PROVIDED, THE INVESTIGATION COULD BE REOPENED. MONITOR THROUGH TREND ANALYSIS. DEPUY CONSIDERS THIS COMPLAINT CLOSED AT THIS TIME.”
* : “MDR Report Key” using in MAUDE database
19
Appendix 4. Characteristics of included clinical studies Study Iannotti 200612 Randomised controlled study
Participants
Intervention
Subjects: Thirty two shoulders in patients with a large (4-5 cm) or massive (>5 cm) chronic tear of the supraspinatus and infraspinatus tendons; open surgical repairs were conducted between January 2002 and January 2004.
Intervention 1 (n=15 shoulders): Patients received open surgical repair and with augmentation with Restore implant. The implant was “sewn to the greater tuberosity at the tendon-bone attachment site and sutured to intact rotator cuff tendon both anterior and posterior”.
Setting: Department of Orthopaedic Surgery and the Orthopaedic Research Centre, Cleveland Clinic Foundation, Cleveland, Ohio
Control (n=15 shoulders): Patients received open surgical repair only.
Gender: male (23) and female (7) Age: mean age 58 yrs, ranged from 41 to 70 yrs Inclusion criteria: 1). A tear of both the supraspinatus and the infraspinatus tendons documented by preoperative magnetic resonance imaging, 2). an age greater than 18 yrs, 3). A tear of at least three months duration, and 4). A fully repairable tear as determined by
Follow up: average 14 months. Two patients were unable or refused to undergo MRI examination at the one year follow up. These two patients were not included in the analysis.
Outcomes
Comments and authors’ conclusion
Rotator cuff healed (assessed by MRI examination 1 yr after surgery )
Block randomisation used
Intervention Control
Assessor blinded ?
4/15 9/15
Small sample size After adjustment for the effect of tear size on the rate of healing , repairs without augmentation were found to be 7% more likely to heal than augmented repairs (odds ratio, 1.07, p=0.07) Median PENN score (The University of Pennsylvania Shoulder Scale) at the end of follow up: Total score (P=0.07) Intervention 83 Control 91 Function score (P=0.03) Intervention 52 Control 57 Pain score (P=0.18) Intervention 25 Control 29 Satisfaction score (P=0.09) Intervention 8 Control 10
Two patients who did not complete the follow up MRI scanning were not included in the analysis Evidence level: 1Authors’ conclusions “ augmentation of the surgical repair of large and massive chronic rotator cuff tears with porcine small intestine submucosa did not improve the rate of tendon healing or the clinical outcome scores. On the basis of these data, we do not recommend using porcine small intestine submocosa to augment repairs of massive
Change from pre-operation to post-operation PENN score (%):
intra-operative assessment. Exclusion criteria: 1). Prior shoulder surgery, 2). Cervical spinal disease, 3). A frozen shoulder, and 4). Glenohumeral arthritis.
Total score (P=0.26) Intervention 117% Control 153% Function score (P=0.48) Intervention 122% Control 177% Pain score (P=0.13) Intervention 46% Control 114% Satisfaction score (P=0.09) Intervention 187% Control 350% Adverse events in three patients were found in the intervention group.
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chronic rotator cuff tears ”
Sclamberg 2004 14 Case series
Subjects: Eleven consecutive patients with large (1) and massive (10) rotator cuff tears, surgeries were performed between September 2000 and September 2001. All patients in this study had extensive atrophy and retraction of their supraspinatus and infraspinatus. Setting: Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California
Surgical treatment: open procedure was performed with release and reattachment of the deltoid; an acromioplasty was done in 6 patients; tendons were partially reattached to the greater tuberosity with suture anchors or thick nonabsorbable sutures through bone. Restore implant was used as an inter-positional graft in 7 repairs, and as reinforcement in 5 repairs.
The American Shoulder and Elbow Pain score (P=0.7): Pre-operation Post-operation
60.3 (mean) 58.4 (mean)
Case series---lack of comparison group Relatively short term of follow up
Rerupture (postoperative MRI scan): 10/11 (91%) One patient had an intact repair on MRI at 10 month, with improved shoulder score from 60 to 65.
Unclear about when the postoperative questionnaire undertaken
Five patients had worse shoulder scores postoperatively.
Small sample size
Standard postoperative protocols and rehabilitation were undertaken.
Pain improved in 7 patients, unchanged in 3 patients, and increased in 1 patient.
Evidence level: 3
Follow up: At lease 6 months (range 6 – 10 months),
All patients had weakness of the supraspinatus and external rotators on rotator cuff testing.
Gender: female and male Range of motion did not change after surgery compared with preoperative status.
Age: mean age 67.5, ranged from 52 to 78 yrs
Pre-operation Post-operation
0.53 (SD=0.64) 0.60 (SD=0.63)
Frequency of awakening (0=never wake up, 1= awaken 1 to 2 times a week, 2=3 to 6 times a week, 3=7 times or more) Pre-operation Post-operation
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0.27 (SD=0.80) 0.20 (SD=0.56)
Authors’ conclusion “on the basis of our results, we do not recommend the use of interpositional porcine SIS xenografts for large and massive rotator cuff tears, especially those with atrophy.”
Walton 2007 15
Modified case series study, compared with a retrospectively matched control group The original study design was a RCT which was then abandoned due to safety concern of inflammatory
Subjects: 19 patients with large to massive rotator cuff tears, and received conventional rotator cuff repair with Restore patch. Mean tear size was 9.1cm. 16 control patients who only received conventional surgical treatment without the implant, also came from the original RCT study, and retrospectively matched with mean age, mean tear size and gender ratio. All these patients and most controls received surgical treatment in the period between April 2002 and January 2003.
reaction.
Setting: Orthopaedic Research Institute, University of New South Wales, Australia Gender: female and male Age: mean age 60.2 yrs (59.6 yrs in the control group)
Restore implant group: 19 patients underwent diagnostic arthroscopy followed by conventional rotator cuff repair by a single surgeon. Restore patch was placed over the top of the rotator cuff repair as an augmentation patch.
Activity related Pain score at 3 months after surgery (P
