Clinical trial NCT01498029: Knee Articular Cartilage Repair: Cartilage Autograft Implantation System Versus Conventional Microfracture
Official title: A Randomised Clinical Trial Comparing a Novel Single-stage Autologous Cartilage Implantation System to Conventional Microfracture for Repair of Articular Cartilage Defects in the Knee
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Other Articular Cartilage Disorders
Osteochondritis Dissecans
Keywords: Cartilage, Articular
Lead sponsor: Singapore General Hospital
Sponsor class: OTHER
First posted: 2011-12-23
Enrollment: 36
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Cartilage Autograft Implantation System (CAIS) is a single-stage procedure in which cartilage is harvested from non-critical regions of articular cartilage, but then immediately morcellated and loaded onto a polymer membrane-scaffold, which is subsequently used to fill the chondral defect. The autograft-membrane composite is fixed to the defect with a biodegradable staple.

The investigators aim to evaluate this new technique through a pilot clinical trial involving 36 patients randomized into microfracture and CAIS treatment arms (randomisation ratio 1:2), with a minimum follow-up of 1 year, using both clinical and radiological (magnetic resonance imaging) outcomes. If the results of this pilot trial are successful, the investigators plan to expand the study by recruiting more patients to achieve a suitably-powered trial.

Primary hypothesis 1: That functional scores will increase by at least 0.5 SD over pre-operative values, by 1 year following the CAIS procedure

Primary hypothesis 2: That articular cartilage height will have a sustained increase of at least 2 mm at 1 year following the CAIS procedure

Primary hypothesis 3: That functional scores in the CAIS group will be equivalent or superior to those in the microfracture group

Detailed description: Articular cartilage has limited potential for regeneration, and full-thickness cartilage defects in the knee are frequently symptomatic and debilitating. If left untreated, such injuries may progress to generalized osteoarthritis. The management of these injuries remains unsatisfactory despite intense research activity, and the clinical and social impact of this problem is growing, involving as it often does the young and the active.

Numerous surgical techniques have been developed to treat these injuries, but none has yet been shown to be superior. One of the most widely employed and best-studied means of achieving cartilage repair in patients with discrete regions of chondral destruction in the knee is that of microfracture. Microfracture is an arthroscopic technique that involves penetrating the subchondral bone at the base of full-thickness articular cartilage defects, thus allowing marrow pluripotent stem cells to egress into the chondral defect, facilitating cartilage repair. However, doubts have been raised concerning the quality and durability of the microfracture-induced repair tissue. In recent years, autologous chondrocyte implantation (ACI) has emerged as the technique with the greatest potential for advancing the management of chondral injury. In this procedure, autologous chondrocytes are harvested from non-critical areas on the articular surface, then expanded through cell culture in the laboratory, before being implanted 4-6 weeks later into the chondral defect, using a 'patch' of adjacent periosteum for containment of the cells within the defect. There are several disadvantages to the ACI technique just described: it is a two-stage procedure, chondrocyte culture can be lengthy and expensive, and the periosteal patch used to contain the cells is associated with a significant risk of complications such as detachment and hypertrophy. 2nd generation ACI techniques have focused on addressing some of these problems by substituting the periosteum patch with artificial membranes that served as scaffolds for the cultured chondrocytes.

A novel technique has recently been developed that could prove to avoid some of the deficiencies of the ACI technique. The Cartilage Autograft Implantation System (CAIS) is a single-stage procedure in which cartilage is harvested from non-critical regions of articular cartilage, but then immediately morcellated and loaded onto a polymer membrane-scaffold, which is subsequently used to fill the chondral defect. The autograft-membrane composite is fixed to the defect with a biodegradable staple.

We aim to evaluate this new technique through a pilot clinical trial involving 36 patients randomized into microfracture and CAIS treatment arms (randomisation ratio 1:2), with a minimum follow-up of 1 year, using both clinical and radiological (magnetic resonance imaging) outcomes. If the results of this pilot trial are successful, we plan to expand the study by recruiting more patients to achieve a suitably-powered trial.

Primary hypothesis 1: That functional scores will increase by at least 0.5 SD over pre-operative values, by 1 year following the CAIS procedure

Primary hypothesis 2: That articular cartilage height will have a sustained increase of at least 2 mm at 1 year following the CAIS procedure

Primary hypothesis 3: That functional scores in the CAIS group will be equivalent or superior to those in the microfracture group

Eligibility criteria: Inclusion Criteria:

* Full-thickness articular cartilage defect on the femoral condyle or trochlea greater than 2 cm2 but less than 10 cm2 in total surface area, following debridement to healthy, stable tissue.
* Knee mechanical axis malalignment of not more than 3 degrees either varus or valgus from neutral.
* Patient is fit for surgery.

Exclusion Criteria:

* Multifocal disease
* Tibial plateau lesions
* Patella lesions
* Absent menisci or meniscal tears that are unstable and cannot be successfully debrided
* Non-intact cruciate and collateral ligaments
* Inflammatory or crystalline arthropathy
* Systemic medication or conditions likely to compromise chondrocyte cell proliferation and differentiation, e.g. Cushing's syndrome, chemotherapy
* Morbid obesity (more than 150% ideal body weight)

Primary outcomes:
measure: MR Observations of Cartilage Repair Tissue
timeFrame: 3 weeks post operative
measure: MR Observations of Cartilage Repair Tissue
timeFrame: 6 months post-operative
measure: MR Observations of Cartilage Repair Tissue
timeFrame: 1 year post-operative
Secondary outcomes:
measure: Assessment of whole leg mechanical alignment
timeFrame: 1 week prior to surgery
measure: Assessment of whole leg mechanical alignment
timeFrame: 1 month post-operative
measure: Assessment of whole leg mechanical alignment
timeFrame: 3 month post-operative
measure: Assessment of whole leg mechanical alignment
timeFrame: 6 month post-operative
measure: Assessment of whole leg mechanical alignment
timeFrame: 1 year post-operative
measure: Clinical and functional evaluation using standardised and validated scoring system
timeFrame: 1 week prior to surgery
measure: Clinical and functional evaluation using standardised and validated scoring system
timeFrame: 1 month post-operative
measure: Clinical and functional evaluation using standardised and validated scoring system
timeFrame: 3 month post-operative
measure: Clinical and functional evaluation using standardised and validated scoring system
timeFrame: 6 month post-operative
measure: Clinical and functional evaluation using standardised and validated scoring system
timeFrame: 1 year post-operative
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Singapore General Hospital
Study officials:
affiliation: Singapore General Hospital
name: Shi-Lu Chia, PhD, MBBS
role: PRINCIPAL_INVESTIGATOR
References: