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.
see above
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
118
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.
A procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue.
AZ St. Jan Brugge, Department of Orthopedics
Bruges, Belgium
AZ St Lucas Brugge, Department of Orthopedics
Bruges, Belgium
Academisch Ziekenhuis, Vrije Universiteit Brussel, Department of Orthopedics
Brussels, Belgium
SPM Monica Antwerp
Deurne, Belgium
Ghent University Hospital, Department of Orthopedics
Ghent, Belgium
AZ St. Elisabeth, Department of Orthopedics
Herentals, Belgium
AZ Groeninge, Department of Orthopedics
Kortrijk, Belgium
University Hospitals Leuven, Department of Orthopedics
Leuven, Belgium
A.Z. Sint Jozef, Department of Orthopedics
Malle, Belgium
Department of Orthopedic Surgery, School of Medicine, University of Zagreb
Zagreb, Croatia
...and 2 more locations
Histomorphometry Safranin-O + Anti-Collagen II Antibody Staining
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.
Time frame: 12 months post-surgery
Overall Histology Assessment on First Subscale of ICRS II Score
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)
Time frame: 12 months post-surgery
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 Months (Average)
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.
Time frame: Average change from baseline in Overall KOOS at 12-18 months post-surgery
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 36 Months
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.
Time frame: Change from baseline in Overall KOOS at 36 months post-surgery
Number of Treatment Failures at 36 Months
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.
Time frame: Continuous
Safety: Adverse Events
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).
Time frame: continuous up to 60 months
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