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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 118
- 试验地点
- 12
- 主要终点
- Histomorphometry Safranin-O + Anti-Collagen II Antibody Staining
研究概览
简要总结
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.
详细描述
see above
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed patient informed consent
- •Symptomatic cartilage single lesion of the femoral condyle
- •Lesion on femoral condyle between 1 and 5 cm²
- •Agree to participate actively in a strict rehabilitation protocol and follow-up programme
- •Agree to only use paracetamol mono-or combination preparation (max 4g/d) and Non-Steroidal Anti Inflammatory Drugs (NSAIDS) during the study and to discontinue this medication 2 weeks before the baseline visit and the follow-up visits. The use of paracetamol mono-preparation (max 4g/d) is allowed up to one week before the baseline visit and the follow-up visits.
- •Females of childbearing age should use a proven method to prevent pregnancy
排除标准
- •Participation in concurrent trials
- •Participation in previous trials within 3 months
- •Subjects with hepatitis, HIV or syphilis
- •Malignancy
- •Alcohol or drug (medication) abuse
- •Poor general health as judged by Investigator
- •Clinically relevant second cartilage lesion on the patella
- •Patellofemoral cartilage lesion
- •Osteochondritis Dissecans (OCD) : recent OCD (within 1 year before baseline), depth of lesion > 0.5cm, subchondral slerosis
- •Advanced osteoarthritis (OA) : radiographic atlas of OA grade 2-3
- •Known allergy to gentamicin or penicillins (or presence of multiple severe allergies)
- •Complex ligamentous instability of the knee
- •Meniscal transplant
- •Meniscal suture with meniscal arrows (ipsilateral)
- •Meniscus resection : if < 1 yr before baseline - lateral meniscus resection or medial meniscus resection of more than 50%. If > 1 yr before baseline - ipsilateral meniscus resection of more than 50%, controlateral meniscus resection of more than 50% if ipsilateral meniscus is not intact, combination of medial and lateral meniscus resection and one of both > 50%.
- •Varus or valgus malalignment of more than 5°
- •Mosaicplasty
- •Microfracture performed less than 1 yr before baseline
- •Having received hyaluronic acid intra-articular injections in the affected knee within the last 6 months of baseline
- •Taking specific OA drugs such as chondroïtin sulfate, diacerein, n-glucosamine, piascledine, capsaicin within 2 weeks of the baseline visit
- •Corticosteroïd treatment by systemic or intra-articular route within the last month of baseline or intramuscular or oral corticosteroïds within the last 2 weeks of baseline
- •Chronic use of anticoagulants
- •Uncontrolled diabetes
- •Any concomitant painful or disabling disease of the spine,hips or lower limbs that would interfere with evaluation of the afflicted knee
- •Any clinically significant or symptomatic vascular or neurologic disorder of the lower extremities
- •Any evidence of the following diseases in the target joint : septic arthritis, inflammatory joint disease, gout, recurrent episodes of pseudogout, Paget's disease of bone, ochronosis, acromegaly, hemochromatosis, Wilson's disease, primary osteochondromatosis, heritable disorders, collagen gene mutation
- •Current diagnosis of osteomyelitis
- •Liver enzymes (SGOT, SGPT, Alkaline Phosphatase) of more then two times the upper limit of normal or any other result that is clinically important according to the Investigator
- •CRP > 10 mg/l
研究组 & 干预措施
ChondroCelect
干预措施: ChondroCelect implantation (Drug)
Microfracture
干预措施: Microfracture (Procedure)
结局指标
主要结局
Histomorphometry Safranin-O + Anti-Collagen II Antibody Staining
时间窗: 12 months post-surgery
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
时间窗: 12 months post-surgery
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)
时间窗: Average change from baseline in Overall KOOS at 12-18 months post-surgery
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.
次要结局
- Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 36 Months(Change from baseline in Overall KOOS at 36 months post-surgery)
- Number of Treatment Failures at 36 Months(Continuous)
- Safety: Adverse Events(continuous up to 60 months)