Knee Articular Cartilage Repair: Cartilage Autograft Implantation System Versus Conventional Microfracture (CAIS)

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

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

Study Overview

• Status: Unknown
• Conditions: Osteochondritis Dissecans; Other Articular Cartilage Disorders
• Intervention / Treatment: Procedure: Microfracture; Device: Cartilage Autograft Implantation System (CAIS)

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

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 3

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 169608
    • Recruiting
    • Singapore General Hospital
    • Contact: Shi-Lu Chia, PhD, MBBS; Phone Number: +65 9817 1102; Email: chia.shi.lu@sgh.com.sg
    • Principal Investigator: Shi-Lu Chia, PhD, MBBS
    • Sub-Investigator: Seng Jin Yeo, FRCS, MBBS
    • Sub-Investigator: Zhihong Zhou, BEng
    • Sub-Investigator: Andy Yew, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Randomized to Microfracture; This group of patients who have been randomised to receive microfracture procedure will be the control group for this study	Procedure: Microfracture; The microfracture procedure is a standard method for treatment of cartilage damage in which the surgeon will clean the site of your cartilage damage and then will make several small holes in your bone to stimulate your bone marrow with the intention to repair the damaged area with new cartilage tissue; Other Names: Knee; Cartilage; Cartilage Repair
EXPERIMENTAL: Randomized to CAIS; This group of patients who have been randomised to receive the CAIS procedure will be the experimental group for this study	Device: Cartilage Autograft Implantation System (CAIS); The Cartilage Autograft Implantation System (CAIS) is a kit of devices that utilizes morselized autologous hyaline cartilage harvested arthroscopically, affixed onto a synthetic, resorbable implant using a fibrin sealant and implanted in a single surgical procedure. The system is designed as a surgical treatment of damaged knee cartilage using the subject's own healthy cartilage obtained from a non-weight or low weight-bearing region.; Other Names: Knee; Cartilage; Cartilage Repair

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MR Observations of Cartilage Repair Tissue	The MOCART (MR Observations of Cartilage Repair Tissue) scoring system, which has been well validated in studies of cartilage regeneration techniques, will be used to assess the cartilage repair response	3 weeks post operative
MR Observations of Cartilage Repair Tissue	The MOCART (MR Observations of Cartilage Repair Tissue) scoring system, which has been well validated in studies of cartilage regeneration techniques, will be used to assess the cartilage repair response	6 months post-operative
MR Observations of Cartilage Repair Tissue	The MOCART (MR Observations of Cartilage Repair Tissue) scoring system, which has been well validated in studies of cartilage regeneration techniques, will be used to assess the cartilage repair response	1 year post-operative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of whole leg mechanical alignment	Standard weight-bearing plain radiographs of the knee, as well as long leg standing films to assess mechanical alignment, will also be performed.	1 week prior to surgery
Assessment of whole leg mechanical alignment	Standard weight-bearing plain radiographs of the knee, as well as long leg standing films to assess mechanical alignment, will also be performed.	1 month post-operative
Assessment of whole leg mechanical alignment	Standard weight-bearing plain radiographs of the knee, as well as long leg standing films to assess mechanical alignment, will also be performed.	3 month post-operative
Assessment of whole leg mechanical alignment	Standard weight-bearing plain radiographs of the knee, as well as long leg standing films to assess mechanical alignment, will also be performed.	6 month post-operative
Assessment of whole leg mechanical alignment	Standard weight-bearing plain radiographs of the knee, as well as long leg standing films to assess mechanical alignment, will also be performed.	1 year post-operative
Clinical and functional evaluation using standardised and validated scoring system	Pre- and post-operative assessment (1,3,6 and 12 months) of the diseased knee will be performed using standardised, validated scoring systems: SF-36 (general health), KOOS and ICRS (disease-specific) scores	1 week prior to surgery
Clinical and functional evaluation using standardised and validated scoring system	Pre- and post-operative assessment (1,3,6 and 12 months) of the diseased knee will be performed using standardised, validated scoring systems: SF-36 (general health), KOOS and ICRS (disease-specific) scores	1 month post-operative
Clinical and functional evaluation using standardised and validated scoring system	Pre- and post-operative assessment (1,3,6 and 12 months) of the diseased knee will be performed using standardised, validated scoring systems: SF-36 (general health), KOOS and ICRS (disease-specific) scores	3 month post-operative
Clinical and functional evaluation using standardised and validated scoring system	Pre- and post-operative assessment (1,3,6 and 12 months) of the diseased knee will be performed using standardised, validated scoring systems: SF-36 (general health), KOOS and ICRS (disease-specific) scores	6 month post-operative
Clinical and functional evaluation using standardised and validated scoring system	Pre- and post-operative assessment (1,3,6 and 12 months) of the diseased knee will be performed using standardised, validated scoring systems: SF-36 (general health), KOOS and ICRS (disease-specific) scores	1 year post-operative

Collaborators and Investigators

• Sponsor: Singapore General Hospital
• Investigators: Principal Investigator: Shi-Lu Chia, PhD, MBBS, Singapore General Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ANTICIPATED): December 1, 2013
• Study Completion (ANTICIPATED): December 1, 2014

Study Registration Dates

• First Submitted: December 7, 2011
• First Submitted That Met QC Criteria: December 22, 2011
• First Posted (ESTIMATE): December 23, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): March 21, 2012
• Last Update Submitted That Met QC Criteria: March 20, 2012
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: Cartilage, Articular
• Additional Relevant MeSH Terms: Fractures, Bone; Wounds and Injuries; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Cartilage Diseases; Fractures, Stress; Osteochondritis; Osteochondritis Dissecans
• Other Study ID Numbers: CART/ 5 April 2011