Other Articular Cartilage DisordersPhase 3CAISNCT01498029
Knee Articular Cartilage Repair: Cartilage Autograft Implantation System Versus Conventional Microfracture
A Phase 3 study testing Microfracture and Cartilage Autograft Implantation System (CAIS) in people with Other Articular Cartilage Disorders and Osteochondritis Dissecans, run by Singapore General Hospital at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 50 years
- Conditions the study is for
- Other Articular Cartilage Disorders, Osteochondritis Dissecans
- What is being tested?
- Microfracture and Cartilage Autograft Implantation System (CAIS)
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteSingapore
- Study dates
- Jan 2012to Dec 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
Singapore General Hospital
Singapore, 169608
Shi-Lu Chia, PhD, MBBS, +65 9817 1102, chia.shi.lu@sgh.com.sg
Shi-Lu Chia, PhD, MBBS
About this study
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
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.
Read more
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
Read the 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
- Being tested
- Microfracture, Cartilage Autograft Implantation System (CAIS)
- Keywords
- Cartilage, Articular
- Medical subject headings
- Osteochondritis Dissecans
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MicrofractureProcedure or surgery
Also called Knee, Cartilage, Cartilage Repair
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
Cartilage Autograft Implantation System (CAIS)Device
Also called Knee, Cartilage, Cartilage Repair
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.
| Study group | Role | What they receive |
|---|---|---|
| Randomized to Microfracture | Active comparator | This group of patients who have been randomised to receive microfracture procedure will be the control group for this study Receives: Procedure: Microfracture |
| Randomized to CAIS | Experimental | This group of patients who have been randomised to receive the CAIS procedure will be the experimental group for this study Receives: Device: Cartilage Autograft Implantation System (CAIS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 1 year post-operative
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 1 year post-operative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2011 (estimated)
- Study startJan 2012
- Primary completionDec 2013 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Other Articular Cartilage DisordersStudies of the same condition, open and under way.
- More trials run by Singapore General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shi-Lu Chia, PhD, MBBS, Principal investigator, Singapore General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01498029
- Sponsor's protocol ID
- CART/ 5 April 2011
- Acronym
- CAIS
- Status last verified
- Dec 2011
- First submitted
- 7 Dec 2011
- Last updated
- 21 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01498029
- Acronym / sponsor ID
- CAIS / CART/ 5 April 2011
- Keywords
- Cartilage, Articular
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Singapore General HospitalUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 23 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Randomized to Microfracture | Active comparator | Procedure: MicrofractureThis group of patients who have been randomised to receive microfracture procedure will be the control group for this study |
| Randomized to CAIS | Experimental | Device: Cartilage Autograft Implantation System (CAIS)This group of patients who have been randomised to receive the CAIS procedure will be the experimental group for this study |
Who may qualify
- Ages
- 21 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MicrofractureAlso: Knee, Cartilage, Cartilage RepairThe 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 | Procedure or surgery | Randomized to Microfracture |
| Cartilage Autograft Implantation System (CAIS)Also: Knee, Cartilage, Cartilage RepairThe 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. | Device | Randomized to CAIS |
Primary outcome
MR Observations of Cartilage Repair Tissue
Time frame: 3 weeks post operative
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
MR Observations of Cartilage Repair Tissue
Time frame: 6 months post-operative
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
MR Observations of Cartilage Repair Tissue
Time frame: 1 year post-operative
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
10 secondary outcomes
Assessment of whole leg mechanical alignment
Time frame: 1 week prior to surgery
Assessment of whole leg mechanical alignment
Time frame: 1 month post-operative
Assessment of whole leg mechanical alignment
Time frame: 3 month post-operative
Assessment of whole leg mechanical alignment
Time frame: 6 month post-operative
Assessment of whole leg mechanical alignment
Time frame: 1 year post-operative
Clinical and functional evaluation using standardised and validated scoring system
Time frame: 1 week prior to surgery
Clinical and functional evaluation using standardised and validated scoring system
Time frame: 1 month post-operative
Clinical and functional evaluation using standardised and validated scoring system
Time frame: 3 month post-operative
Clinical and functional evaluation using standardised and validated scoring system
Time frame: 6 month post-operative
Clinical and functional evaluation using standardised and validated scoring system
Time frame: 1 year post-operative
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shi-Lu Chia, PhD, MBBS principal investigator
Singapore General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Microfracture and Cartilage Autograft Implantation System (CAIS) in people with Other Articular Cartilage Disorders and Osteochondritis Dissecans, run by Singapore General Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shi-Lu Chia, PhD, MBBS (+65 98171 102, chia.shi.lu@sgh.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MR Observations of Cartilage Repair Tissue (time frame: 3 weeks post operative). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2012.