RCT of ChondroCelect® (in an ACI Procedure) vs Microfracture in the Repair of Cartilage Defects of the Knee (TIGACT01)
This is a phase III, multicenter, open-label, randomized controlled trial of ChondroCelect® in an Autologous Chondrocyte Implantation (ACI) procedure compared to the procedure of microfracture (MF) in the repair of symptomatic cartilage lesions of the knee. Eligible patients attended two screening visits and were booked for arthroscopy approximately 2 weeks later. At that time, patients were randomized to either ACI with ChondroCelect® or to MF, a procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue. Patients randomized to MF had the procedure performed at the time of their arthroscopy; those randomized to ACI with ChondroCelect® had their cells harvested during the arthroscopy and then returned to the clinic approximately 4 weeks later for an open knee procedure, during which the ACI procedure using ChondroCelect® was performed. Patients subsequently followed the same rehabilitation program and had follow-up assessments up to 12 months post-surgery. The 12-month visit was the end-of-study visit for the TIG/ACT/01/2000 protocol. Subject to satisfying the eligibility criteria, patients who had participated in the initial 12 month trial could enter the extension trial. The 12-month visit for the initial study was the baseline visit for the extension study. During the extension study, patients have follow-up assessments up to 60 months post-surgery.
Articular Cartilage Lesion of the Femoral Condyle
Drug: ChondroCelect implantation
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Prospective Multicenter Randomized Controlled Trial of ChondroCelect® (Via Autologous Chondrocyte Implantation) vs Microfracture (as Procedure) in the Repair of Symptomatic Cartilaginous Defects of the Femoral Condyles|
- Histomorphometry Safranin-O + Anti-Collagen II Antibody Staining [ Time Frame: 12 months post-surgery ] [ Designated as safety issue: No ]Histomorphometry on end point biopsies at 12 months post-surgery. Safranin-O (ratio 0-1)+ anti-Collagen II antibody (ratio 0-1) stain signal expressed as a ratio of the total cartilage surface area (Saf O + anti Coll II divided by total surface = ratio 0-2). Safranin-O stains proteoglycans and anti-Collagen II antibody reflects the presence of Collagen II.
- Overall Histology Assessment on First Subscale of ICRS II Score [ Time Frame: 12 months post-surgery ] [ Designated as safety issue: No ]Overall histology assessment of cartilage repair, first subscale of International Cartilage Repair Society II (ICRS II) score by two blinded independant histopathologists on a visual analogue scale (VAS 0-100mm) from worst (0) to best (100)
- Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 Months (Average) [ Time Frame: Average change from baseline in Overall KOOS at 12-18 months post-surgery ] [ Designated as safety issue: No ]Overall Knee injury and Osteoarthritis Outcome score (average of 4 KOOS subdomains, Sports not included) at the average of 12-18 months (calculated by averaging change from baseline measurements at 12 and 18 months). Best score = 100; worst score = 0. The analysis was the average of the change from baseline at the 12 and 18 months timepoints.
- Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 36 Months [ Time Frame: Change from baseline in Overall KOOS at 36 months post-surgery ] [ Designated as safety issue: No ]Overall Knee injury and Osteoarthritis Outcome score (average of 4 KOOS subdomains: Activities of Daily Living, Quality of Life, Symptoms and Stiffness Pain; Sports not included) at 36 months (change from baseline). Best = 100; worst = 0.
- Number of Treatment Failures at 36 Months [ Time Frame: Continuous ] [ Designated as safety issue: Yes ]
Participants with failed treatment - defined as the number of patients who underwent a reintervention of the index lesion - at 36 months.
The index lesion is the lesion that was initially treated in the study.
- Safety: Adverse Events [ Time Frame: continuous up to 60 months ] [ Designated as safety issue: Yes ]Side effects are recorded as the number of patients with adverse events. These events are coded according to the Medical Dictionary for Regulatory Affairs (MedDRA terms).
|Study Start Date:||February 2002|
|Study Completion Date:||January 2010|
|Primary Completion Date:||July 2006 (Final data collection date for primary outcome measure)|
Drug: ChondroCelect implantation
10.000 cells/µl cell suspension for implantation (Autologous Chondrocyte Implantation). ChondroCelect consists of characterised autologous cartilage-forming cells expressing a specific marker profile.
The dose depends on the size of the lesion. Recommended dose is 0.8 to 1.0 million cells/cm².
Other Name: CCI
|Active Comparator: Microfracture||
A procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue.
Other Name: subchondral drilling
|AZ St. Jan Brugge, Department of Orthopedics|
|Brugge, Belgium, 8000|
|AZ St Lucas Brugge, Department of Orthopedics|
|Brugge, Belgium, 8310|
|Academisch Ziekenhuis, Vrije Universiteit Brussel, Department of Orthopedics|
|Brussels, Belgium, 1090|
|SPM Monica Antwerp|
|Deurne, Belgium, 2100|
|Ghent University Hospital, Department of Orthopedics|
|Ghent, Belgium, 9000|
|AZ St. Elisabeth, Department of Orthopedics|
|Herentals, Belgium, 2200|
|AZ Groeninge, Department of Orthopedics|
|Kortrijk, Belgium, 8500|
|University Hospitals Leuven, Department of Orthopedics|
|Leuven, Belgium, 3000|
|A.Z. Sint Jozef, Department of Orthopedics|
|Malle, Belgium, 2390|
|Department of Orthopedic Surgery, School of Medicine, University of Zagreb|
|Zagreb, Croatia, 10000|
|University Hospital Hannover, Department of Orthopedics|
|Hannover, Germany, 30625|
|University Medical Center Utrecht, Department of Orthopedics|
|Utrecht, Netherlands, 3584|
|Principal Investigator:||Daniël BF Saris, M.D., Ph.D.||University Medical Center Utrecht, Department of Orthopedics, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.|
|Principal Investigator:||Johan Vanlauwe, M.D.||University Hospitals Leuven, Department of Orthopedics, Herestraat 49, 3000 Leuven, Weligerveld 1, 3212 Pellenberg, Belgium.|
|Study Director:||Frank P Luyten, M.D., Ph.D.||Division of Rheumatology, Department of Muskuloskeletal Sciences, University Hospitals, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium|