Superiority of MACI® Versus Microfracture Treatment in Patients With Symptomatic Articular Cartilage Defects in the Knee (SUMMIT)
|ClinicalTrials.gov Identifier: NCT00719576|
Recruitment Status : Completed
First Posted : July 21, 2008
Results First Posted : December 14, 2017
Last Update Posted : December 14, 2017
|Condition or disease||Intervention/treatment||Phase|
|Articular Cartilage Defect||Biological: autologous cultured chondrocytes on porcine collagen membrane Procedure: Microfracture||Phase 3|
This is a prospective, randomized, open-label, parallel-group, multicenter study designed to investigate the outcome of MACI implant versus arthroscopic microfracture in the treatment of articular cartilage defects in the knee in patients between ages of 18 and 55 years.
All patients who meet the eligibility criteria and are considered suitable for inclusion will have a cartilage biopsy taken prior to randomization to study treatment. Eligible patients will then be randomized during the index arthroscopy procedure to receive either MACI implant or microfracture treatment.
Patients randomized to treatment with MACI implant will return within approximately 4 to 8 weeks of the index arthroscopy to undergo the chondrocyte implantation procedure via arthrotomy. Patients randomized to microfracture will undergo the procedure during the index arthroscopy.
Patients will be assessed post-arthroscopy and post-arthrotomy at intervals during 2 years follow-up. Evaluations include adverse events, functional and pain outcomes, arthroscopic and histologic evaluation and magnetic resonance imaging (MRI).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||144 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Prospective, Randomized, Open-label, Parallel-group, Multi-center Study to Demonstrate the Superiority of MACI® Versus Arthroscopic Microfracture for the Treatment of Symptomatic Articular Cartilage Defects of the Femoral Condyle Including the Trochlea.|
|Study Start Date :||July 2008|
|Actual Primary Completion Date :||March 2012|
|Actual Study Completion Date :||March 2012|
autologous cultured chondrocytes on porcine collagen membrane
Biological: autologous cultured chondrocytes on porcine collagen membrane
Implantation via mini-arthrotomy
Active Comparator: Microfracture
Microfracture performed by arthroscopic surgery
- Change From Baseline to Week 104 for the Participant's Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain and Function (Sports and Recreational Activities) Scores. [ Time Frame: Baseline and Week 104 ]The KOOS is a validated knee-specific instrument developed to assess the patients' opinion of their knee and associated problems. KOOS consists of 5 subscales: Pain, Function in sports and recreational activities, other Symptoms, Function in activities of daily living (ADL), and knee related Quality of life (QOL). A 5-point Likert scale was used to record the response to each item ranging from 0 (no problems) to 4 (extreme problems). Within each subscale, items were added up and normalized to a value between 0 (extreme problems) and 100 (no problems). Subscales are not combined to calculate a total score.
- Histological Evaluation of Structural Repair of Evaluable Biopsies Harvested From the Core of the Index Lesion During Arthroscopy at Week 104 [ Time Frame: Week 104 ]
The mean microscopic International Cartilage Repair Society (ICRS) II overall assessment score was used to assess the histology efficacy endpoint.
Scoring of the cartilage repair biopsies was completed using the ICRS II histology scoring system (Mainil-Varlet, 2010, Am J Sports Med) by 2 independent pathologists blinded to the patient's assigned study treatment. This scoring system includes 14 parameters, comprising an overall assessment score reported here, as well as 13 other items related to chondrocyte phenotype, tissue structure, and other factors, each scored on a scale from 0 to 100 representing poor to good quality cartilage.
- Assessment of Defect Fill by Magnetic Resonance Imaging (MRI) [ Time Frame: Week 104 ]
Number of participants with MRI degree of defect fill > 50%. Evaluation of MRI data was performed by independent central review blinded to the participant's treatment.
Appropriate MRI sequences were used to image cartilage repair tissue.
- Response Rate Based on KOOS Pain and Function (Sports and Recreational Activities) Scores at Week 104. [ Time Frame: Week 104 ]A responder is defined as a participant with at least a 10-point improvement in both the KOOS Pain and Function (Sports and Recreational activities) scores from Baseline
- Treatment Failure [ Time Frame: Week 104 ]
The planned analyses concerning time to treatment failure were not conducted due to the small number of per protocol treatment failure cases. As such, the number of participants with treatment failure is being reported.
Patients were considered as a treatment failure if all of the following 5 criteria were met:
- Patient's global assessment of their knee joint compared to Baseline was the same or worse
- Physician's global assessment of the patient's knee joint compared to Baseline was the same, worse, or significantly worse.
- Percent improvement from Baseline in KOOS Pain score was less than 10%.
- Physician diagnostic evaluation of failure excluded etiologies (eg, meniscal tear) other than failed treatment of the index lesion.
- The physician decided that surgical re-treatment of the index lesion(s) was required that involved either extensive debridement for lesion expansion, violation of the subchondral bone, or autologous cultured chondrocyte implantation.
- Change From Baseline at Week 104 in the Remaining 3 Subscales of the KOOS Instrument (Activities of Daily Living, Knee-related Quality of Life, and Other Symptoms) [ Time Frame: Baseline and Week 104 ]The KOOS is a validated knee-specific instrument developed to assess the patients' opinion of their knee and associated problems. KOOS consists of 5 subscales: Pain, Function in sports and recreational activities, other Symptoms, Function in activities of daily living (ADL), and knee related Quality of life (QOL). A 5-point Likert scale was used to record the response to each item ranging from 0 (no problems) to 4 (extreme problems). Within each subscale, items were added up and normalized to a value between 0 (extreme problems) and 100 (no problems).
- Participants With Treatment-Emergent Adverse Events [ Time Frame: Week 104 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00719576
|Urazova nemocnice v Brne|
|Fakultni Nemocnice Na Bulovce|
|Fakultni Nemocnice v Motole|
|Hopital d'instruction des armees Robert Picque|
|Centre Hospitalier Lyon Sud|
|Chirurgien Orthopediste et Traumatologue du Sport, Institut de I'Appareil Locomoteur Nollet|
|Academisch Ziekenhuis Maastricht|
|St. Elisabeth Ziekenhuis|
|St Olavs Hospital|
|Regional Hospital of Traumatologic Surgery|
|Piekary Slaskie, Poland|
|Center for Sports Medicine CMS|
|Medical Academy Warsaw|
|Capio Artro Clinic AB|
|The South West London Elective Orthopaedic Centre (SWLEOC)|
|Epsom, United Kingdom|
|Nuffield Dept. of Orthopaedic Surgery, University of Oxford|
|Oxford, United Kingdom|
|Spire Cheshire Hospital|
|Warrington, United Kingdom|
|Study Director:||Medical Monitor||Genzyme, a Sanofi Company|