RCT of ChondroCelect® (in an ACI Procedure) vs Microfracture in the Repair of Cartilage Defects of the Knee
Condition: Articular Cartilage Lesion of the Femoral Condyle
MeSH terms: Fractures, Stress
Intervention: ChondroCelect implantation; Microfracture
Intervention description: 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.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 118.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Cartilage; Articular; Femoral; Knee

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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