A Randomized Controlled Trial Comparing Chondro-Gide® to Microfracture Alone for Treatment of Knee Cartilage Defects.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of using Chondro-Gide® collagen membrane either sutured or glued compared to microfracture alone in the treatment of symptomatic cartilage defects of the knee.

Detailed Description
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Prospective, randomized, active treatment-controlled, open-label multicenter study (up to 40 sites in the US and EU). All subjects that meet preoperative screening eligibility criteria will be randomized to treatment with Chondro-Gide® either sutured or glued or Microfracture alone. Eligible and consenting subjects are randomized in a 1:1:1 ratio using centralized randomization list to receive one of the following treatments: Group I: Microfracture alone; Group II: Microfracture covered with a Chondro-Gide® membrane glued with fibrin glue (AMIC glued); Group III: Microfracture covered with a Chondro-Gide® membrane sutured (AMIC sutured) All subjects will be assessed at intervals post-procedure (6 weeks, 3 months, and 1,2 and 5 years). Subjects will be required to follow a strict pre-specified post-surgery rehabilitation protocol specific to the defect location. Measures to assess effectiveness and safety will be conducted at all follow-ups. Safety will be assessed by the collection of adverse events at all timepoints.

Official Title
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Randomised Multi-Center Study: Microfracturing With Chondro-Gide® for the Treatment of Isolated Cartilage Defects in the Knee Project-Nr.: 10830-003

Conditions
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Cartilage Injury, Osteochondritis Dissecans

Intervention / Treatment
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* Procedure: Microfracture
* Device: Chondro-Gide sutured
* Device: Chondro-Gide glued


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between 18 and 50 One or two cartilage defects Grade III or IV according to Outerbridge classification Defect size between 2 and 10 cm2 (inclusive) Intact normal surrounding cartilage to suture the Chondro-Gide® membrane Informed consent Patient willing to fulfill a strict postoperative physiotherapy scheme Exclusion Criteria: More than 2 defects Defects on both knees X-ray signs of osteoarthritis Bone lesion > 0.7 cm in the defect Knee instability, varus or valgus deformation, status after complete meniscus resection, status after mosaicplasty, patella dysplasia Rheumatoid, infectious disease Skin lesion on the operated knee Treatment with cartilage building medication Drug and alcohol abuse Chronic heart disease, endocrine or metabolic disease, Haemophilia A/B Pregnancy or lactation Collagen allergy Participation in other Trials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: microfracture<br>Microfracture is an arthroscopic surgical technique involving placement of microfracture penetrations within the cartilage defect to provide stem cells and growth factors from the bone marrow to aid cartilage repair | Procedure: Microfracture<br>* Microfracture is a well-established arthroscopic surgical technique for cartilage repair which involves several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect, with resultant complete defect fill by a well-anchored clot<br>|
| Experimental: Microfracture with Chondro-Gide sutured<br>Microfracture covered with a collagen membrane (Chondro-Gide®) using atraumatic sutures in a one-step mini-arthrotomy procedure | Device: Chondro-Gide sutured<br>* Implantation of Chondro-Gide membrane using atraumatic sutures following microfracture via mini-arthrotomy<br>|
| Experimental: Microfracture with Chondro-Gide glued<br>Microfracture covered with a collagen membrane (Chondro-Gide®) using fibrin glue in a one-step mini-arthrotomy procedure | Device: Chondro-Gide glued<br>* Implantation of Chondro-Gide membrane using Fibrin glue following microfracture via mini-arthrotomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological evaluation of structural repair of evaluable biopsies harvested from the core of the index lesion during arthroscopy at 2 years | The macroscopically assessed integration, surface properties and extent of filling of the defect and the microscopically assessed using the International Cartilage Repair Society (ICRS) score | 2 years post-surgery | 
| MRI (magnetic resonance imaging) assessment of structural repair parameters. | Structural repair is assessed with magnetic resonance imaging (MRI, 1.5T) by an independent and blinded radiologist, with a focus on the extent, signal intensity and surface of the defect filling, integration to adjacent cartilage, and bone marrow lesion (BML). | 6 months and 1,2 and 5 years post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the patient's evaluation of overall knee condition using the Modified Cincinnati Knee Rating System. | The Change from Baseline will be evaluated. | 6 months and 1,2 and 5 years post-surgery | 
| Change from Baseline in the patient's evaluation of pain using the Visual Analog Scale (VAS). | The Change from Baseline will be evaluated. | 6 months and 1,2 and 5 years post-surgery | 
| Change from Baseline in the patient's evaluation of overall knee condition using the International Cartilage Repair Society (ICRS) Cartilage Injury Evaluation Package. | The Change from Baseline will be evaluated. | 6 months and 1,2 and 5 years post-surgery | 
| Adverse Events (AE) Review | The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE), will be collected for all participants. | 5 years post-surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chondro-Gide®, microfracture, enhanced marrow stimulation, articular cartilage, Autologous Matrix-Induced Chondrogenesis, knee surgery, AMIC