Articular Cartilage DefectPhase 3SUMMITNCT00719576
Superiority of MACI® Versus Microfracture Treatment in Patients With Symptomatic Articular Cartilage Defects in the Knee
A Phase 3 study testing autologous cultured chondrocytes on porcine collagen membrane and Microfracture in people with Articular Cartilage Defect, run by Vericel Corporation at 20 sites in 7 countries.
Trial summary
The objective of this trial is to demonstrate superior efficacy and safety of MACI compared with arthroscopic microfracture in the treatment of patients (aged 18 to 55 years) with symptomatic articular cartilage defects of the knee. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Articular Cartilage Defect
- What is being tested?
- autologous cultured chondrocytes on porcine collagen membrane and Microfracture
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 20 sitesin 7 countries
- Study dates
- Jul 2008to Mar 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Symptomatic, single or multiple full-thickness cartilage defects of the knee with or without bone involvement
Who cannot join
- Known history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin
- Severe osteoarthritis of the knee
- Inflammatory arthritis, inflammatory joint disease, or uncorrected congenital blood coagulation disorders
- Prior knee surgery (within 6 months), excluding surgery to procure a biopsy or a concomitant procedure to prepare the knee for a MACI implant.
Trial locations and contacts
20 sites in 7 countries.
20 sites in 7 countries
France4 sites
Hopital d'instruction des armees Robert Picque
Bordeaux
Centre Hospitalier Lyon Sud
Lyon
Polyclinique Saint-Roch
Montpellier
Chirurgien Orthopediste et Traumatologue du Sport, Institut de I'Appareil Locomoteur Nollet
Paris
Poland4 sites
Szpital Uniwersytecki
Bydgoszcz
Regional Hospital of Traumatologic Surgery
Piekary Śląskie
Center for Sports Medicine CMS
Warsaw
Medical Academy Warsaw
Warsaw
Czechia3 sites
Urazova nemocnice v Brne
Brno
Fakultni Nemocnice Na Bulovce
Prague
Fakultni Nemocnice v Motole
Prague
Netherlands3 sites
Academisch Ziekenhuis Maastricht
Maastricht
St. Elisabeth Ziekenhuis
Tilburg
UMC Utrecht
Utrecht
United Kingdom3 sites
The South West London Elective Orthopaedic Centre (SWLEOC)
Epsom
Nuffield Dept. of Orthopaedic Surgery, University of Oxford
Oxford
Spire Cheshire Hospital
Warrington
About this study
Official title: A Prospective, Randomized, Open-label, Parallel-group, Multi-center Study to Demonstrate the Superiority of MACI® Versus Arthroscopic Microfracture for the Treatment of Symptomatic Articular Cartilage Defects of the Femoral Condyle Including the Trochlea.
The objective of this trial is to demonstrate superior efficacy and safety of MACI compared with arthroscopic microfracture in the treatment of patients (aged 18 to 55 years) with symptomatic articular cartilage defects of the knee.
Read the detailed description
This is a prospective, randomized, open-label, parallel-group, multicenter study designed to investigate the outcome of MACI implant versus arthroscopic microfracture in the treatment of articular cartilage defects in the knee in patients between ages of 18 and 55 years.
All patients who meet the eligibility criteria and are considered suitable for inclusion will have a cartilage biopsy taken prior to randomization to study treatment. Eligible patients will then be randomized during the index arthroscopy procedure to receive either MACI implant or microfracture treatment.
Patients randomized to treatment with MACI implant will return within approximately 4 to 8 weeks of the index arthroscopy to undergo the chondrocyte implantation procedure via arthrotomy. Patients randomized to microfracture will undergo the procedure during the index arthroscopy.
Patients will be assessed post-arthroscopy and post-arthrotomy at intervals during 2 years follow-up. Evaluations include adverse events, functional and pain outcomes, arthroscopic and histologic evaluation and magnetic resonance imaging (MRI).
- Conditions
- Articular Cartilage Defect
- Being tested
- autologous cultured chondrocytes on porcine collagen membrane, Microfracture
- Keywords
- Cartilage legions, symptomatic focal cartilage defects, microfracture, MACI, autologous chondrocyte
- Medical subject headings
- Fractures, Stress
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
autologous cultured chondrocytes on porcine collagen membraneBiological
Also called MACI, matrix-applied characterized autologous cultured chondrocytes
Implantation via mini-arthrotomy
MicrofractureProcedure or surgery
Microfracture performed by arthroscopic surgery
| Study group | Role | What they receive |
|---|---|---|
| MACI | Experimental | autologous cultured chondrocytes on porcine collagen membrane Receives: Biological: autologous cultured chondrocytes on porcine collagen membrane |
| Microfracture | Active comparator | Microfracture Receives: Procedure: Microfracture |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 104 for the Participant's Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain and Function (Sports and Recreational Activities) Scores.
The KOOS is a validated knee-specific instrument developed to assess the patients' opinion of their knee and associated problems. KOOS consists of 5 subscales: Pain, Function in sports and recreational activities, other Symptoms, Function in activities of daily living (ADL), and knee related Quality of life (QOL). A 5-point Likert scale was used to record the response to each item ranging from 0 (no problems) to 4 (extreme problems). Within each subscale, items were added up and normalized to a value between 0 (extreme problems) and 100 (no problems). Subscales are not combined to calculate a total score.
Measured: Baseline and Week 104
Secondary outcomes (6)
Histological Evaluation of Structural Repair of Evaluable Biopsies Harvested From the Core of the Index Lesion During Arthroscopy at Week 104
The mean microscopic International Cartilage Repair Society (ICRS) II overall assessment score was used to assess the histology efficacy endpoint.
Scoring of the cartilage repair biopsies was completed using the ICRS II histology scoring system (Mainil-Varlet, 2010, Am J Sports Med) by 2 independent pathologists blinded to the patient's assigned study treatment. This scoring system includes 14 parameters, comprising an overall assessment score reported here, as well as 13 other items related to chondrocyte phenotype, tissue structure, and other factors, each scored on a scale from 0 to 100 representing poor to good quality cartilage.
Measured: Week 104
Assessment of Defect Fill by Magnetic Resonance Imaging (MRI)
Number of participants with MRI degree of defect fill > 50%. Evaluation of MRI data was performed by independent central review blinded to the participant's treatment.
Appropriate MRI sequences were used to image cartilage repair tissue.
Measured: Week 104
Response Rate Based on KOOS Pain and Function (Sports and Recreational Activities) Scores at Week 104.
A responder is defined as a participant with at least a 10-point improvement in both the KOOS Pain and Function (Sports and Recreational activities) scores from Baseline
Measured: Week 104
Treatment Failure
The planned analyses concerning time to treatment failure were not conducted due to the small number of per protocol treatment failure cases. As such, the number of participants with treatment failure is being reported.
Patients were considered as a treatment failure if all of the following 5 criteria were met:
- Patient's global assessment of their knee joint compared to Baseline was the same or worse
- Physician's global assessment of the patient's knee joint compared to Baseline was the same, worse, or significantly worse.
- Percent improvement from Baseline in KOOS Pain score was less than 10%.
- Physician diagnostic evaluation of failure excluded etiologies (eg, meniscal tear) other than failed treatment of the index lesion.
- The physician decided that surgical re-treatment of the index lesion(s) was required that involved either extensive debridement for lesion expansion, violation of the subchondral bone, or autologous cultured chondrocyte implantation.
Measured: Week 104
Change From Baseline at Week 104 in the Remaining 3 Subscales of the KOOS Instrument (Activities of Daily Living, Knee-related Quality of Life, and Other Symptoms)
The KOOS is a validated knee-specific instrument developed to assess the patients' opinion of their knee and associated problems. KOOS consists of 5 subscales: Pain, Function in sports and recreational activities, other Symptoms, Function in activities of daily living (ADL), and knee related Quality of life (QOL). A 5-point Likert scale was used to record the response to each item ranging from 0 (no problems) to 4 (extreme problems). Within each subscale, items were added up and normalized to a value between 0 (extreme problems) and 100 (no problems).
Measured: Baseline and Week 104
Participants With Treatment-Emergent Adverse Events
Measured: Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Articular Cartilage DefectStudies of the same condition, open and under way.
- 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
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vericel Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00719576
- Sponsor's protocol ID
- MACI00206
- Other IDs
- 2006-004817-16
- Acronym
- SUMMIT
- Status last verified
- May 2021
- First submitted
- 17 Jul 2008
- Last updated
- 12 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Saris D, Price A, Widuchowski W, Bertrand-Marchand M, Caron J, Drogset JO, Emans P, Podskubka A, Tsuchida A, Kili S, Levine D, Brittberg M; SUMMIT study group. Matrix-Applied Characterized Autologous Cultured Chondrocytes Versus Microfracture: Two-Year Follow-up of a Prospective Randomized Trial. Am J Sports Med. 2014 Jun;42(6):1384-94. doi: 10.1177/0363546514528093. Epub 2014 Apr 8.
PubMed 24714783
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Open-label, Parallel-group, Multi-center Study to Demonstrate the Superiority of MACI® Versus Arthroscopic Microfracture for the Treatment of Symptomatic Articular Cartilage Defects of the Femoral Condyle Including the Trochlea.
- ClinicalTrials.gov ID
- NCT00719576
- Acronym / sponsor ID
- SUMMIT / MACI00206
- Conditions
- Articular Cartilage Defect
- Keywords
- Cartilage legions, symptomatic focal cartilage defects, microfracture, MACI, autologous chondrocyte
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- Vericel CorporationIndustry (pharma, biotech, devices)
- Study start
- Jul 2008
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 21 Jul 2008 (estimated)
- Results
- Posted 14 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this trial is to demonstrate superior efficacy and safety of MACI compared with arthroscopic microfracture in the treatment of patients (aged 18 to 55 years) with symptomatic articular cartilage defects of the knee.
Detailed description
This is a prospective, randomized, open-label, parallel-group, multicenter study designed to investigate the outcome of MACI implant versus arthroscopic microfracture in the treatment of articular cartilage defects in the knee in patients between ages of 18 and 55 years.
All patients who meet the eligibility criteria and are considered suitable for inclusion will have a cartilage biopsy taken prior to randomization to study treatment. Eligible patients will then be randomized during the index arthroscopy procedure to receive either MACI implant or microfracture treatment.
Patients randomized to treatment with MACI implant will return within approximately 4 to 8 weeks of the index arthroscopy to undergo the chondrocyte implantation procedure via arthrotomy. Patients randomized to microfracture will undergo the procedure during the index arthroscopy.
Patients will be assessed post-arthroscopy and post-arthrotomy at intervals during 2 years follow-up. Evaluations include adverse events, functional and pain outcomes, arthroscopic and histologic evaluation and magnetic resonance imaging (MRI).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MACI | Experimental | Biological: autologous cultured chondrocytes on porcine collagen membraneautologous cultured chondrocytes on porcine collagen membrane |
| Microfracture | Active comparator | Procedure: MicrofractureMicrofracture |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Symptomatic, single or multiple full-thickness cartilage defects of the knee with or without bone involvement
Key exclusion criteria (4 listed)
- Known history of hypersensitivity to gentamicin, other aminoglycosides, or products of porcine or bovine origin
- Severe osteoarthritis of the knee
- Inflammatory arthritis, inflammatory joint disease, or uncorrected congenital blood coagulation disorders
- Prior knee surgery (within 6 months), excluding surgery to procure a biopsy or a concomitant procedure to prepare the knee for a MACI implant.
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 |
|---|---|---|
| autologous cultured chondrocytes on porcine collagen membraneAlso: MACI, matrix-applied characterized autologous cultured chondrocytesImplantation via mini-arthrotomy | Biological | MACI |
| MicrofractureMicrofracture performed by arthroscopic surgery | Procedure or surgery | Microfracture |
Primary outcome
Change From Baseline to Week 104 for the Participant's Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain and Function (Sports and Recreational Activities) Scores.
Time frame: Baseline and Week 104
The KOOS is a validated knee-specific instrument developed to assess the patients' opinion of their knee and associated problems. KOOS consists of 5 subscales: Pain, Function in sports and recreational activities, other Symptoms, Function in activities of daily living (ADL), and knee related Quality of life (QOL). A 5-point Likert scale was used to record the response to each item ranging from 0 (no problems) to 4 (extreme problems). Within each subscale, items were added up and normalized to a value between 0 (extreme problems) and 100 (no problems). Subscales are not combined to calculate a total score.
6 secondary outcomes
Histological Evaluation of Structural Repair of Evaluable Biopsies Harvested From the Core of the Index Lesion During Arthroscopy at Week 104
Time frame: Week 104
Assessment of Defect Fill by Magnetic Resonance Imaging (MRI)
Time frame: Week 104
Response Rate Based on KOOS Pain and Function (Sports and Recreational Activities) Scores at Week 104.
Time frame: Week 104
Treatment Failure
Time frame: Week 104
Change From Baseline at Week 104 in the Remaining 3 Subscales of the KOOS Instrument (Activities of Daily Living, Knee-related Quality of Life, and Other Symptoms)
Time frame: Baseline and Week 104
Participants With Treatment-Emergent Adverse Events
Time frame: Week 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24714783Saris D, Price A, Widuchowski W, Bertrand-Marchand M, Caron J, Drogset JO, Emans P, Podskubka A, Tsuchida A, Kili S, Levine D, Brittberg M; SUMMIT study group. Matrix-Applied Characterized Autologous Cultured Chondrocytes Versus Microfracture: Two-Year Follow-up of a Prospective Randomized Trial. Am J Sports Med. 2014 Jun;42(6):1384-94. doi: 10.1177/0363546514528093. Epub 2014 Apr 8.
- Individual participant dataSharing planned: No
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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.
Medical Monitor study director
Genzyme, a Sanofi Company
20 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing autologous cultured chondrocytes on porcine collagen membrane and Microfracture in people with Articular Cartilage Defect, run by Vericel Corporation at 20 sites in 7 countries.
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 1 inclusion and 4 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: finished, as of the sponsor's last update on 12 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in France, Poland, Czechia, Netherlands, United Kingdom and 2 more countries. 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?
Yes. Results are posted in the registry (first posted 14 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 104 for the Participant's Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain and Function (Sports and Recreational Activities) Scores. (time frame: Baseline and Week 104). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00719576, which also lists 1 linked publication.
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 12 May 2021; AzTrials last refreshed its copy on 7 Nov 2026.