Clinical Registry Assessment of the Missouri Osteochondral Allograft Preservation System - MOPS

Study Overview
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Brief Summary
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With institutional review board approval and informed consent, patients are prospectively enrolled into a registry to follow outcomes after osteochondral allograft (OCA) and/or meniscal allograft transplantation. Patients are included when 1 year followup data are available, including complications and reoperations, patient reported outcome measures (PROMs), compliance with rehabilitation, revisions, and failures. In addition, MOPS grafts are compared to standard preservation grafts, and unipolar, multisurface, and bipolar cohorts, as well as patient compliance variables, are compared.

Detailed Description
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With institutional review board approval and documented informed consent, patients are prospectively enrolled into a dedicated registry designed to follow outcomes after OCA transplantation with or without meniscal allograft transplantation. All grafts are obtained from tissue banks accredited by the American Association of Tissue Banks (AATB) and used in conformance of the tissue to the US Food and Drug Administration classification of a human cell and tissue product under section 361 of the Public Health Services Act. Initially, standard preservation (SP) grafts stored in refrigeration in proprietary solutions for 21 days after recovery from 1 of 3 AATB accredited tissue banks were used. As a separate arm, first clinical use of Missouri Osteochondral Preservation System (MOPS) grafts, which are stored at room temperature using MOPS methods for up to 56 days after recovery from 1 AATB accredited tissue bank, was assessed. In phase 2, after MOPS grafts became commercially available, type of graft implanted was based on patient-matched graft availability. Then, on the basis of emerging evidence published in the peer-reviewed medical literature, we implemented a shift in practice to discontinue use of SP grafts at our center. Surgery is performed on patients with at least one large focal full-thickness articular cartilage defect and/or functional deficiency of 1 or both menisci for knee patients, and for hip, ankle or shoulder patients with at least 1 large focal full-thickness defect who chose this treatment option over other nonsurgical or surgical options as indicated and were approved for coverage by their insurance provider. OCA transplantation surgery is performed using press-fit cylindrical grafts and/or custom-cut patient-specific tab-in-slot shell grafts stabilized with either screws, bioabsorbable pins, or bioabsorbable nails. OCA bone is saturated with autogenous bone marrow aspirate concentrate (Angel System; Arthrex, Inc) immediately before implantation after subchondral drill holes are created and the donor bone is thoroughly lavaged to remove marrow elements. Meniscal allograft transplants (fresh or fresh frozen) are performed via a bone plug technique with suspensory fixation or included as part of the tibial OCA transplant. Viable chondrocyte density of OCAs at the time of transplantation are determined when tissues are available, as previously described. Procedure-specific postoperative management protocols are prescribed to each patient undergoing allograft transplantation. All patients receive oral and written instructions regarding postoperative rehabilitation. Data are collected preoperatively and at 6 weeks, 3 months, 6 months, and yearly after surgery for each case. Demographic and operative data are collected from the electronic medical record. Patient-reported outcome measures (PROMs) are collected at each time point. All reported complications and reoperations are recorded in the electronic medical record. Revision is defined as a second operation to revise the osteochondral and/or meniscal allograft in at least 1 part of the patient's joint, and failure is defined as conversion to total or partial artificial joint arthroplasty, joint fusion, or amputation. The decision to pursue revision or failure surgery is based on the attending surgeon's discussion of joint pathology, treatment options, and related prognosis in conjunction with patient preference. Successful outcomes are defined as patients reporting return to functional activities with no need for revision or conversion surgery at last recorded follow-up. Descriptive statistics are calculated to report means, ranges, and percentages. On the basis of the difference in graft preservation methodology, cases are also analyzed by cohort as defined by SP versus MOPS. On the basis of surgery type, cases are also analyzed by cohort as defined by unipolar, multisurface, or bipolar transplants. Chi-square or Fisher exact tests are used to assess for significant differences in proportions. When significant differences in proportions are noted, odds ratios are calculated for relevant comparisons. One-way analysis of variance or t tests are used to assess for significant differences among cohorts at respective time points. Repeated measures analyses of variance are used to assess for significant differences within cohorts over time. Kaplan-Meier survival probability estimates with 95% CIs are calculated and compared. Significance is set at P<.05.

Official Title
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Clinical Assessment of the Missouri Osteochondral Allograft Preservation System: Lifelong Registry

Conditions
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Symptomatic Osteochondral Defect(s), Cartilage, Meniscus, Ankle, Knee, Shoulder, Hip

Intervention / Treatment
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* Procedure: Standard of care osteochondral and or meniscal allograft transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults and children age ≥13 years Knee, hip, ankle, or shoulder osteochondral defect ≥15mm as determined by MRI or diagnostic knee arthroscopy for allograft transplantation Must be physically and mentally willing and able to comply with postoperative and routinely scheduled clinical and radiographic evaluations. Must be able to read and understand English or a language for which translated versions of the patient reported questionnaires and Informed consent form are available. Must be able to sign informed consent and must voluntarily sign the Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved subject Informed Consent Form. Exclusion Criteria: Is a prisoner Is receiving workman's compensation Subject is mentally incompetent such that would preclude the subject from providing adequate consent and/or complying with study requirements

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MOPS<br>Transplanted tissue preserved using the MOPS method and obtained from one AATB-approved tissue bank | Procedure: Standard of care osteochondral and or meniscal allograft transplantation<br>* Standard of care osteochondral and or meniscal allograft transplantation<br>|
| Standard Preservation<br>Transplanted tissue preserved using standard preservation methods and obtained from one of three AATB-approved tissue banks | Procedure: Standard of care osteochondral and or meniscal allograft transplantation<br>* Standard of care osteochondral and or meniscal allograft transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Knee Documentation Committee (IKDC) | The International Knee Documentation Committee (IKDC) Subjective Knee Form is a patient-oriented questionnaire that assesses symptoms and function in daily living activities. | annually up to 29 years | 
| PROMIS survey (PROMIS Bank v1.2 - Physical Function) | PROMIS® stands for Patient Reported Outcomes Measurement Information System, which is a system of highly reliable, precise measures of patient-reported health status for physical, mental, and social well-being. In this particular case, this survey assesses the patient's physical function. | annually up to 29 years | 
| Visual Analogue Scale (VAS) Pain Score | The visual analog scale (VAS) is a tool widely used to measure pain. A patient is asked to indicate his/her perceived pain intensity (most commonly) along a 10 cm horizontal line, and this rating is then measured from the left edge (=VAS score) | annually up to 29 years | 
| Single Assessment Numeric Evaluation (SANE) | SANE is a patient rating from 0-100. Patients rate their current illness score in relation to their pre-injury baseline. | annually up to 29 years | 
| Success, Revision, Failure | Revision is defined as a second operation to revise the osteochondral and/or meniscal allograft in at least 1 part of the patient's joint, and failure is defined as conversion to artificial arthroplasty, arthrodesis, or amputation. Successful outcomes are defined as patients reporting return to functional activities with no revision or failure at last recorded follow-up. | annually up to 29 years | 
| PROMIS survey (PROMIS Bank v1.2 - Physical Function - Mobility | PROMIS® stands for Patient Reported Outcomes Measurement Information System, which is a system of highly reliable, precise measures of patient-reported health status for physical, mental, and social well-being. In this particular case, this survey assesses the patient's mobility. | annually up to 29 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PROMIS survey (PROMIS Bank v1.1 - Pain Interference) | PROMIS® stands for Patient Reported Outcomes Measurement Information System, which is a system of highly reliable, precise measures of patient-reported health status for physical, mental, and social well-being. In this particular case, this survey assesses how the patient's pain interferes with their general life style. | annually up to 29 years | 
| Standard of Care (SOC) Diagnostic Imaging | When the study patient attends their standard-of-care visits with their primary surgeon, the surgeon may or may not order diagnostic radiological imaging (X-Ray, MRI) depending on their medical judgment. If such radiological imaging is ordered and the images are available, they will be evaluated to assess the healing and integration of the graft. | Pre-operative, 6 week, 3 month, 6 month, and annually up to 29 years | 
| Blood and Urine Samples | Blood and urine samples will be collected pre-operatively, at each surgical procedure (at the initial surgical procedure and any necessary procedure thereafter), and at each post-operative visit after the initial 2 week visit (6 weeks, 3 months, 6 months, 12 months, 24 months). These samples will be used to evaluate biomarkers associated with tissue inflammation, synthesis, degradation, and cell death. | Pre-operative, Day of Surgery, 6 week, 3 month, 6 month, and annually up to 29 years | 
| Non-SOC MRI | A non-standard-of-care MRI will be taken at the 12 month visit to assess the healing and integration of the graft. | 12 month visit |