AMIC Compared With Microfracture for Focal Articular Cartilage Damage of the Hip

Study Overview
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Brief Summary
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This is a pilot multi-centre RCT of 40 patients (ages 18-40 years, inclusive) undergoing primary hip arthroscopy with a focal articular cartilage defect of the acetabulum to compare the effect of using autologous matrix-induced chondrogenesis (AMIC) in comparison to microfracture on hip function, health-related quality of life, hip pain, cartilage regeneration, health utility, and any adverse events at 2 years. Follow-up will occur at 6 weeks, 6 months, 12 months, 18 months, and 24 months post-surgery.

Official Title
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Autologous MatRix-Induced ChondrogenEsis ComPared With Microfracture for Focal ArtIcular CaRtilage Damage of the Hip (REPAIR): A Pilot Randomized Controlled Trial

Conditions
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Hip Arthroscopy, Articular Cartilage Defect, Microfractures

Intervention / Treatment
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* Procedure: Autologous matrix-induced chondrogenesis (AMIC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged 18-40 years Hip pain lasting 6 months or more with no relief from documented non-operative modalities Focal articular cartilage defects of the acetabulum on MRI, confirmed to be full thickness (International Cartilage Regeneration and Joint Preservation Society (ICRS) grade 3 or 4)37 during arthroscopic examination Focal acetabular articular cartilage lesions measuring between 2x2 cm2 and 5x5 cm2 on MRI and confirmed on arthroscopic examination Patient agrees to participate in the study-specific postoperative rehabilitation protocol Patient can speak, read, and understand the language of the site Patient has provided informed consent Exclusion Criteria: Cartilage defects of the femoral head Previous surgery on the study hip Traumatic chondral injury of the hip from a single event Presence of advanced osteoarthritis (Tonnis grade 2 or 3)38 or any other acute or chronic inflammatory joint disease Known hypersensitivity or allergy to porcine collagen Acute or chronic infection at the surgical site Evidence of hip dysplasia (i.e., lateral centre edge angle < 20˚) Evidence of acetabular over coverage such as coxa profunda or coxa protrusion Immunosuppressive or anti-proliferative medication use Chronic pain syndromes Significant medical co-morbidities (requiring assistance for activities of daily living (ADLs)) History of paediatric hip disease Uncontrolled diabetes Contraindications to MRI imaging (e.g. claustrophobia) Patient is involved in ongoing legal or workplace claims Patient is incarcerated Patient is pregnant or breastfeeding Patient who will likely have problems, in the judgement of the investigator, with maintaining follow-up Any other reason(s) the investigator feels is relevant for excluding the patient

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All patients presenting to each clinical site's out-patient fracture clinics and/or sports medicine subspecialty clinics between ages of 18 and 40 years with a symptomatic chondral injury of the hip will be screened. There will be a Research Coordinator on hand during the initial phase of the surgery for each consented patient, where the surgeon will assess the final aspects of eligibility. If eligibility is confirmed, the Research Coordinator will randomize the patient using a centralized 24-hour online randomization system that will follow a randomization schedule in random block sizes of 4 and 8. The secure online randomization system will ensure concealment of the treatment allocation. If the surgeon deems intra-operatively that the subject does not meet the inclusion criteria, the surgeon will manage the lesion as per the normal standard of care and the subject's ineligibility will be recorded on the screening form.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Microfracture<br>As per current standard of care for focal articular cartilage lesions of the acetabulum, the unstable cartilage will be debrided and removed from the subchondral bone using a mechanical shaver until a stable margin is obtained. A ring curette will be used to remove the calcified cartilage layer and create a border of healthy cartilage tissue that can support the marrow clot. Through the mid-anterior portal, specialized 90˚ awls will then be placed with the tip perpendicular to the subchondral bone of the acetabulum, and a mallet will be used to penetrate the subchondral bone with perforations 3 mm deep to access the bone marrow elements. This is done until the defect is homogeneously covered with micro-perforations 2-3 mm apart. | Procedure: Autologous matrix-induced chondrogenesis (AMIC)<br>* AMIC is a novel approach in which the microfracture technique has been enhanced by the use of a type I/III collagen matrix (Chondro-Gide®; Geistlich Pharma AG, Wolhusen, Switzerland). In this single-step procedure, the matrix is placed over the defect to stabilize the fragile blood clot that arises from microfracture and to provide infrastructure for repair tissue formation. Essentially, the matrix covers the defect and serves as a protective shield that contains the cells and minimizes the impact of shear forces when moving the hip on the delicate blood clot. At the same time, it functions as the roof of a biological chamber that forms over the defect. The biocompatible collagen material provides an environment for cell growth and is replaced by native tissue over time.<br>* Other names: Chondro-Gide(R);|
| Experimental: Autologous matrix-induced chondrogenesis (AMIC)<br>Those allocated to the AMIC treatment group will also receive microfracture. Once the walls of the debrided lesion are confirmed to be stable with a probe, the exact size of the defect will be measured for templating of the scaffold. The dry Chondro-Gide® matrix will be prepared by cutting it to 10% smaller than the focal defect (as it increases in size about 10% after moistening). Once the cartilage lesion is dried manually, the implant will then be secured to the defect in a press-fit fashion to the surrounding cartilage. Manual pressure is then applied to secure the implant into the defect and the hip is released from traction and rotated to facilitate further fixation of the graft. Traction is then applied to arthroscopically confirm position and fixation of the implant. | Procedure: Autologous matrix-induced chondrogenesis (AMIC)<br>* AMIC is a novel approach in which the microfracture technique has been enhanced by the use of a type I/III collagen matrix (Chondro-Gide®; Geistlich Pharma AG, Wolhusen, Switzerland). In this single-step procedure, the matrix is placed over the defect to stabilize the fragile blood clot that arises from microfracture and to provide infrastructure for repair tissue formation. Essentially, the matrix covers the defect and serves as a protective shield that contains the cells and minimizes the impact of shear forces when moving the hip on the delicate blood clot. At the same time, it functions as the roof of a biological chamber that forms over the defect. The biocompatible collagen material provides an environment for cell growth and is replaced by native tissue over time.<br>* Other names: Chondro-Gide(R);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hip function and health-related quality of life using the International Hip Outcome Tool (iHOT-33) | The iHOT-33 is designed to measure hip-specific health-related quality of life changes after treatment of active young patients with hip disorders. The total score is calculated as a simple mean of the responses ranging from 0 to 100, with 100 representing the best possible quality-of-life score. | Change from baseline to 24 months post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hip pain using the Visual Analogue Scale (VAS); 100-point scale | To measure hip pain. The total score is calculated as a single response ranging from 0 to 100, with 100 representing the worst possible pain. | Change from baseline to 24 months post-surgery | 
| Cartilage repair using the Modified Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scale (scored from 0-100) | To evaluate cartilage repair in the hip using MRI imaging. The total score is calculated as a simple mean of the responses ranging from 0 to 100, with 100 representing the worst cartilage status. | Change from baseline to 24 months post-surgery | 
| Health utility using the Euro-Qol 5 Dimensions (EQ-5D); index score | Utility-based instrument for use as a measure of health outcome. Health state index scores generally range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health), with higher scores indicating higher health utility. | Change from baseline to 24 months post-surgery | 
| Total number of adverse events | Any reported complications such as infection, additional or revision surgery, hypersensitivity or allergic reactions, and reduced range of motion | 24 months post-surgery |