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Superiority of MACI® Versus Microfracture Treatment in Patients With Symptomatic Articular Cartilage Defects in the Knee (SUMMIT)

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ClinicalTrials.gov Identifier: NCT00719576
Recruitment Status : Completed
First Posted : July 21, 2008
Results First Posted : December 14, 2017
Last Update Posted : December 14, 2017
Sponsor:
Information provided by (Responsible Party):
Vericel Corporation

Brief 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.

Condition or disease Intervention/treatment Phase
Articular Cartilage Defect Biological: autologous cultured chondrocytes on porcine collagen membrane Procedure: Microfracture Phase 3

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 144 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Study Start Date : July 2008
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012

Arm Intervention/treatment
Experimental: MACI
autologous cultured chondrocytes on porcine collagen membrane
Biological: autologous cultured chondrocytes on porcine collagen membrane
Implantation via mini-arthrotomy
Other Names:
  • MACI
  • matrix-applied characterized autologous cultured chondrocytes
Active Comparator: Microfracture
Microfracture
Procedure: Microfracture
Microfracture performed by arthroscopic surgery



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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 ]

    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.


  2. Assessment of Defect Fill by Magnetic Resonance Imaging (MRI) [ Time Frame: Week 104 ]

    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.


  3. Response Rate Based on KOOS Pain and Function (Sports and Recreational Activities) Scores at Week 104. [ Time Frame: 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

  4. Treatment Failure [ Time Frame: Week 104 ]

    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:

    1. Patient's global assessment of their knee joint compared to Baseline was the same or worse
    2. Physician's global assessment of the patient's knee joint compared to Baseline was the same, worse, or significantly worse.
    3. Percent improvement from Baseline in KOOS Pain score was less than 10%.
    4. Physician diagnostic evaluation of failure excluded etiologies (eg, meniscal tear) other than failed treatment of the index lesion.
    5. 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.

  5. 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 ]
    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).

  6. Participants With Treatment-Emergent Adverse Events [ Time Frame: Week 104 ]


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Symptomatic, single or multiple full-thickness cartilage defects of the knee with or without bone involvement

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00719576


Locations
Czechia
Urazova nemocnice v Brne
Brno, Czechia
Fakultni Nemocnice Na Bulovce
Prague, Czechia
Fakultni Nemocnice v Motole
Prague, Czechia
France
Hopital d'instruction des armees Robert Picque
Bordeaux, France
Centre Hospitalier Lyon Sud
Lyon, France
Polyclinique Saint-Roch
Montpellier, France
Chirurgien Orthopediste et Traumatologue du Sport, Institut de I'Appareil Locomoteur Nollet
Paris, France
Netherlands
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands
St. Elisabeth Ziekenhuis
Tilburg, Netherlands
UMC Utrecht
Utrecht, Netherlands
Norway
St Olavs Hospital
Trondheim, Norway
Poland
Szpital Uniwersytecki
Bydgoszcz, Poland
Regional Hospital of Traumatologic Surgery
Piekary Slaskie, Poland
Center for Sports Medicine CMS
Warsaw, Poland
Medical Academy Warsaw
Warsaw, Poland
Sweden
Kungsbacka Hospital
Kungsbacka, Sweden
Capio Artro Clinic AB
Stockholm, Sweden
United Kingdom
The South West London Elective Orthopaedic Centre (SWLEOC)
Epsom, United Kingdom
Nuffield Dept. of Orthopaedic Surgery, University of Oxford
Oxford, United Kingdom
Spire Cheshire Hospital
Warrington, United Kingdom
Sponsors and Collaborators
Vericel Corporation
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company

Publications of Results:
Responsible Party: Vericel Corporation
ClinicalTrials.gov Identifier: NCT00719576     History of Changes
Other Study ID Numbers: MACI00206
2006-004817-16 ( EudraCT Number )
First Posted: July 21, 2008    Key Record Dates
Results First Posted: December 14, 2017
Last Update Posted: December 14, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Vericel Corporation:
Cartilage legions
symptomatic focal cartilage defects
microfracture
MACI
autologous chondrocyte

Additional relevant MeSH terms:
Fractures, Stress
Cartilage Diseases
Fractures, Bone
Wounds and Injuries
Musculoskeletal Diseases
Connective Tissue Diseases