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CompletedNCT00414700TIGACT01Updated Sep 26, 2011Results posted

RCT of ChondroCelect® (in an ACI Procedure) vs Microfracture in the Repair of Cartilage Defects of the Knee

A Phase 3 interventional study of ChondroCelect implantation and Microfracture in Articular Cartilage Lesion of the Femoral Condyle, sponsored by TiGenix n.v.. Completed at 12 sites in 4 countries. Open to participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2011-09-26.

Sponsored by TiGenix n.v. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
118
Allocation
Randomized
Ages
18 Years to 50 Years
Sex
All
01

Study summary

This is a phase III, multicenter, open-label, randomized controlled trial of ChondroCelect® in an Autologous Chondrocyte Implantation (ACI) procedure compared to the procedure of microfracture (MF) in the repair of symptomatic cartilage lesions of the knee. Eligible patients attended two screening visits and were booked for arthroscopy approximately 2 weeks later. At that time, patients were randomized to either ACI with ChondroCelect® or to MF, a procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue. Patients randomized to MF had the procedure performed at the time of their arthroscopy; those randomized to ACI with ChondroCelect® had their cells harvested during the arthroscopy and then returned to the clinic approximately 4 weeks later for an open knee procedure, during which the ACI procedure using ChondroCelect® was performed. Patients subsequently followed the same rehabilitation program and had follow-up assessments up to 12 months post-surgery. The 12-month visit was the end-of-study visit for the TIG/ACT/01/2000 protocol. Subject to satisfying the eligibility criteria, patients who had participated in the initial 12 month trial could enter the extension trial. The 12-month visit for the initial study was the baseline visit for the extension study. During the extension study, patients have follow-up assessments up to 60 months post-surgery.

Read the detailed description

see above

02

Conditions studied

  • Articular Cartilage Lesion of the Femoral Condyle

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Keywords

  • Cartilage
  • Articular
  • Femoral
  • Knee
03

In context

Fractures, Stress

168 studies on the registry are indexed under Fractures, Stress; 41 are open to participants now.

This study's enrollment of 118 is above the median of 66 across 134 interventional studies indexed under Fractures, Stress.

Browse Fractures, Stress studies →

Lead sponsor

TiGenix n.v. is the lead sponsor of 2 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 50 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Signed patient informed consent
  • Symptomatic cartilage single lesion of the femoral condyle
  • Lesion on femoral condyle between 1 and 5 cm²
  • Agree to participate actively in a strict rehabilitation protocol and follow-up programme
  • Agree to only use paracetamol mono-or combination preparation (max 4g/d) and Non-Steroidal Anti Inflammatory Drugs (NSAIDS) during the study and to discontinue this medication 2 weeks before the baseline visit and the follow-up visits. The use of paracetamol mono-preparation (max 4g/d) is allowed up to one week before the baseline visit and the follow-up visits.
  • Females of childbearing age should use a proven method to prevent pregnancy

Exclusion criteria

Exclusion Criteria:

  • Participation in concurrent trials
  • Participation in previous trials within 3 months
  • Subjects with hepatitis, HIV or syphilis
  • Malignancy
  • Alcohol or drug (medication) abuse
  • Poor general health as judged by Investigator
  • Clinically relevant second cartilage lesion on the patella
  • Patellofemoral cartilage lesion
  • Osteochondritis Dissecans (OCD) : recent OCD (within 1 year before baseline), depth of lesion > 0.5cm, subchondral slerosis
  • Advanced osteoarthritis (OA) : radiographic atlas of OA grade 2-3
  • Known allergy to gentamicin or penicillins (or presence of multiple severe allergies)
  • Complex ligamentous instability of the knee
  • Meniscal transplant
  • Meniscal suture with meniscal arrows (ipsilateral)
  • Meniscus resection : if \< 1 yr before baseline - lateral meniscus resection or medial meniscus resection of more than 50%. If > 1 yr before baseline - ipsilateral meniscus resection of more than 50%, controlateral meniscus resection of more than 50% if ipsilateral meniscus is not intact, combination of medial and lateral meniscus resection and one of both > 50%.
  • Varus or valgus malalignment of more than 5°
  • Mosaicplasty
  • Microfracture performed less than 1 yr before baseline
  • Having received hyaluronic acid intra-articular injections in the affected knee within the last 6 months of baseline
  • Taking specific OA drugs such as chondroïtin sulfate, diacerein, n-glucosamine, piascledine, capsaicin within 2 weeks of the baseline visit
  • Corticosteroïd treatment by systemic or intra-articular route within the last month of baseline or intramuscular or oral corticosteroïds within the last 2 weeks of baseline
  • Chronic use of anticoagulants
  • Uncontrolled diabetes
  • Any concomitant painful or disabling disease of the spine,hips or lower limbs that would interfere with evaluation of the afflicted knee
  • Any clinically significant or symptomatic vascular or neurologic disorder of the lower extremities
  • Any evidence of the following diseases in the target joint : septic arthritis, inflammatory joint disease, gout, recurrent episodes of pseudogout, Paget's disease of bone, ochronosis, acromegaly, hemochromatosis, Wilson's disease, primary osteochondromatosis, heritable disorders, collagen gene mutation
  • Current diagnosis of osteomyelitis
  • Liver enzymes (SGOT, SGPT, Alkaline Phosphatase) of more then two times the upper limit of normal or any other result that is clinically important according to the Investigator
  • CRP > 10 mg/l
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
118 participants (actual)

Study arms

  • Experimental
    ChondroCelect

    Drug: ChondroCelect implantation

  • Active comparator
    Microfracture

    Procedure: Microfracture

Interventions

  • DrugChondroCelect implantation

    10.000 cells/µl cell suspension for implantation (Autologous Chondrocyte Implantation). ChondroCelect consists of characterised autologous cartilage-forming cells expressing a specific marker profile. The dose depends on the size of the lesion. Recommended dose is 0.8 to 1.0 million cells/cm².

    Also known as: CCI

  • ProcedureMicrofracture

    A procedure in which the subchondral bone is perforated to allow a bloodcloth to form scar tissue.

    Also known as: subchondral drilling

06

What researchers measure

Primary outcomes

  1. Histomorphometry Safranin-O + Anti-Collagen II Antibody Staining

    Histomorphometry on end point biopsies at 12 months post-surgery. Safranin-O (ratio 0-1)+ anti-Collagen II antibody (ratio 0-1) stain signal expressed as a ratio of the total cartilage surface area (Saf O + anti Coll II divided by total surface = ratio 0-2). Safranin-O stains proteoglycans and anti-Collagen II antibody reflects the presence of Collagen II.

    Time frame: 12 months post-surgery

  2. Overall Histology Assessment on First Subscale of ICRS II Score

    Overall histology assessment of cartilage repair, first subscale of International Cartilage Repair Society II (ICRS II) score by two blinded independant histopathologists on a visual analogue scale (VAS 0-100mm) from worst (0) to best (100)

    Time frame: 12 months post-surgery

  3. Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 Months (Average)

    Overall Knee injury and Osteoarthritis Outcome score (average of 4 KOOS subdomains, Sports not included) at the average of 12-18 months (calculated by averaging change from baseline measurements at 12 and 18 months). Best score = 100; worst score = 0. The analysis was the average of the change from baseline at the 12 and 18 months timepoints.

    Time frame: Average change from baseline in Overall KOOS at 12-18 months post-surgery

Secondary outcomes

  1. Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 36 Months

    Overall Knee injury and Osteoarthritis Outcome score (average of 4 KOOS subdomains: Activities of Daily Living, Quality of Life, Symptoms and Stiffness Pain; Sports not included) at 36 months (change from baseline). Best = 100; worst = 0.

    Time frame: Change from baseline in Overall KOOS at 36 months post-surgery

  2. Number of Treatment Failures at 36 Months

    Participants with failed treatment - defined as the number of patients who underwent a reintervention of the index lesion - at 36 months. The index lesion is the lesion that was initially treated in the study.

    Time frame: Continuous

  3. Safety: Adverse Events

    Side effects are recorded as the number of patients with adverse events. These events are coded according to the Medical Dictionary for Regulatory Affairs (MedDRA terms).

    Time frame: continuous up to 60 months

07

Results

Posted Jan 18, 2010

Participant flow

Recruitment by orthopaedic surgeons (medical clinic). Recruitment period: 21 February 2002 to 23 November 2004.

Participant flow — Overall Study
MilestoneChondroCelectMicrofracture
Started5761
Completed5158
Not completed63

Outcome measures

PrimaryHistomorphometry Safranin-O + Anti-Collagen II Antibody Staining

Histomorphometry on end point biopsies at 12 months post-surgery. Safranin-O (ratio 0-1)+ anti-Collagen II antibody (ratio 0-1) stain signal expressed as a ratio of the total cartilage surface area (Saf O + anti Coll II divided by total surface = ratio 0-2). Safranin-O stains proteoglycans and anti-Collagen II antibody reflects the presence of Collagen II.

Time frame:
12 months post-surgery
Reported as:
Least squares mean · Ratio
Histomorphometry Safranin-O + Anti-Collagen II Antibody Staining
RatioChondroCelectMicrofracture
Histomorphometry Safranin-O + Anti-Collagen II Antibody Staining1.01 ± 0.080.75 ± 0.08
Statistical analysis
  • ChondroCelect vs Microfracture · ANCOVA · p = 0.003Adjusted for age, associated lesion(s) and location of lesion
PrimaryOverall Histology Assessment on First Subscale of ICRS II Score

Overall histology assessment of cartilage repair, first subscale of International Cartilage Repair Society II (ICRS II) score by two blinded independant histopathologists on a visual analogue scale (VAS 0-100mm) from worst (0) to best (100)

Time frame:
12 months post-surgery
Reported as:
Least squares mean · Points on a scale
Overall Histology Assessment on First Subscale of ICRS II Score
Points on a scaleChondroCelectMicrofracture
Overall Histology Assessment on First Subscale of ICRS II Score55.11 ± 3.9844.20 ± 3.74
Statistical analysis
  • ChondroCelect vs Microfracture · ANCOVA · p = 0.010Adjusted for age, associated lesion(s) and location of lesion.
PrimaryChange From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 Months (Average)

Overall Knee injury and Osteoarthritis Outcome score (average of 4 KOOS subdomains, Sports not included) at the average of 12-18 months (calculated by averaging change from baseline measurements at 12 and 18 months). Best score = 100; worst score = 0. The analysis was the average of the change from baseline at the 12 and 18 months timepoints.

Time frame:
Average change from baseline in Overall KOOS at 12-18 months post-surgery
Reported as:
Least squares mean · points on a scale (0-100)
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12-18 Months (Average)
points on a scale (0-100)ChondroCelectMicrofracture
Change in oKOOS16.18 ± 2.4214.37 ± 2.35
Baseline value56.30 ± 13.6159.53 ± 14.95
Value at 12 months73.26 ± 14.6673.10 ± 16.01
Value at 18 months74.73 ± 17.0175.04 ± 14.50
Statistical analysis
  • ChondroCelect vs Microfracture · ANCOVA · Mean difference (final values): 1.81 · 95% CI -3.28 to 6.90Adjusted for baseline Overall KOOS score, age, associated lesion(s) and location of lesion.
SecondaryChange From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 36 Months

Overall Knee injury and Osteoarthritis Outcome score (average of 4 KOOS subdomains: Activities of Daily Living, Quality of Life, Symptoms and Stiffness Pain; Sports not included) at 36 months (change from baseline). Best = 100; worst = 0.

Time frame:
Change from baseline in Overall KOOS at 36 months post-surgery
Reported as:
Mean · Units on a scale
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 36 Months
Units on a scaleChondroCelectMicrofracture
Change in oKOOS21.25 ± 3.6015.83 ± 3.48
Baseline value56.30 ± 1.9159.46 ± 1.98
Value at 36 month78.46 ± 18.7074.47 ± 18.60
SecondaryNumber of Treatment Failures at 36 Months

Participants with failed treatment - defined as the number of patients who underwent a reintervention of the index lesion - at 36 months. The index lesion is the lesion that was initially treated in the study.

Time frame:
Continuous
Reported as:
Number · Participants
Number of Treatment Failures at 36 Months
ParticipantsChondroCelectMicrofracture
Number of Treatment Failures at 36 Months27
SecondarySafety: Adverse Events

Side effects are recorded as the number of patients with adverse events. These events are coded according to the Medical Dictionary for Regulatory Affairs (MedDRA terms).

Time frame:
continuous up to 60 months
Reported as:
Number · participants
Safety: Adverse Events
participantsChondroCelectMicrofracture
Safety: Adverse Events5161
Post-hocChange From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 60 Months

Patient-administered instrument to assess the patients opinion about their knee and associated problems. It consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life QOL. The last week is taken into consideration when answering questions. Standardized answer options are given (5 Likert boxes) and each question gets a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The result can be plotted as an outcome profile.

Time frame:
60 months
Reported as:
Mean · units on a scale
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 60 Months
units on a scaleChondroCelectMicrofracture
Change From Baseline in Overall Knee Injury and Osteoarthritis Outcome Score (KOOS) at 60 Months21.17 ± 2.8914.07 ± 2.54
Post-hocNumber of Treatment Failures at 60 Months Post-surgery

Participants with failed treatment - defined as the number of patients who underwent a reintervention of the index lesion - at 60 months. The index lesion is the lesion that was initially treated in the study.

Time frame:
60 months
Reported as:
Number · participants
Number of Treatment Failures at 60 Months Post-surgery
participantsChondroCelectMicrofracture
Number of Treatment Failures at 60 Months Post-surgery710

Adverse events

Collected over From baseline up to 36 months database lock. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
ChondroCelect—10/51 (19.6%)50/51 (98%)
Microfracture—12/61 (19.7%)51/61 (83.6%)
Most frequent serious events
Showing 10 of 32
Most frequent serious events
EventChondroCelectMicrofracture
arthralgia (knee pain)Musculoskeletal and connective tissue disorders2/510/61
Synovial cystMusculoskeletal and connective tissue disorders0/512/61
Cerebrovascular accidentNervous system disorders1/510/61
Deep vein thrombosisVascular disorders1/510/61
HaemorrhoidsGastrointestinal disorders1/510/61
HypersensitiviyImmune system disorders1/510/61
Ligament ruptureInjury, poisoning and procedural complications1/510/61
MyopiaEye disorders1/510/61
Retinal detachmentEye disorders1/510/61
TendonitisMusculoskeletal and connective tissue disorders1/510/61
Most frequent other events
Showing 10 of 33
Most frequent other events
EventChondroCelectMicrofracture
ArthralgiaMusculoskeletal and connective tissue disorders38/5137/61
Cartilage hypertrophyMusculoskeletal and connective tissue disorders14/518/61
NasopharyngitisInfections and infestations14/5110/61
InfluenzaInfections and infestations11/5116/61
Joint effusionMusculoskeletal and connective tissue disorders13/517/61
Joint swellingMusculoskeletal and connective tissue disorders11/514/61
Joint crepitationMusculoskeletal and connective tissue disorders10/514/61
HeadacheNervous system disorders4/5111/61
Back painMusculoskeletal and connective tissue disorders8/5110/61
Therapeutic product ineffectiveGeneral disorders4/519/61

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)ChondroCelectMicrofractureTotal
<=18 years000
Between 18 and 65 years5761118
>=65 years000
Age Continuous
Age Continuous(years)ChondroCelectMicrofractureTotal
Mean33.93 ± 8.5433.92 ± 8.6133.92 ± 8.54
Sex: Female, Male
Sex: Female, Male(Participants)ChondroCelectMicrofractureTotal
Female222042
Male354176
Region of Enrollment
Region of Enrollment(participants)ChondroCelectMicrofractureTotal
Belgium333568
Croatia459
Germany145
Netherlands191736
08

Study locations

12 sites
  • AZ St. Jan Brugge, Department of Orthopedics
    Brugge, 8000, Belgium
  • AZ St Lucas Brugge, Department of Orthopedics
    Brugge, 8310, Belgium
  • Academisch Ziekenhuis, Vrije Universiteit Brussel, Department of Orthopedics
    Brussels, 1090, Belgium
  • SPM Monica Antwerp
    Deurne, 2100, Belgium
  • Ghent University Hospital, Department of Orthopedics
    Ghent, 9000, Belgium
  • AZ St. Elisabeth, Department of Orthopedics
    Herentals, 2200, Belgium
  • AZ Groeninge, Department of Orthopedics
    Kortrijk, 8500, Belgium
  • University Hospitals Leuven, Department of Orthopedics
    Leuven, 3000, Belgium
  • A.Z. Sint Jozef, Department of Orthopedics
    Malle, 2390, Belgium
  • Department of Orthopedic Surgery, School of Medicine, University of Zagreb
    Zagreb, 10000, Croatia
  • University Hospital Hannover, Department of Orthopedics
    Hannover, 30625, Germany
  • University Medical Center Utrecht, Department of Orthopedics
    Utrecht, 3584, Netherlands
09

References and documents

Publications

  • Dell'Accio F, Vanlauwe J, Bellemans J, Neys J, De Bari C, Luyten FP. Expanded phenotypically stable chondrocytes persist in the repair tissue and contribute to cartilage matrix formation and structural integration in a goat model of autologous chondrocyte implantation. J Orthop Res. 2003 Jan;21(1):123-31. doi: 10.1016/S0736-0266(02)00090-6. Erratum In: J Orthop Res. 2003 May;21(3):572. PubMed 12507589 ↗
  • Dell'Accio F, De Bari C, Luyten FP. Microenvironment and phenotypic stability specify tissue formation by human articular cartilage-derived cells in vivo. Exp Cell Res. 2003 Jul 1;287(1):16-27. doi: 10.1016/s0014-4827(03)00036-3. PubMed 12799178 ↗
  • Dell'Accio F, De Bari C, Luyten FP. Molecular markers predictive of the capacity of expanded human articular chondrocytes to form stable cartilage in vivo. Arthritis Rheum. 2001 Jul;44(7):1608-19. doi: 10.1002/1529-0131(200107)44:73.0.CO;2-T. PubMed 11465712 ↗
  • Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994 Oct 6;331(14):889-95. doi: 10.1056/NEJM199410063311401. PubMed 8078550 ↗
  • Knutsen G, Engebretsen L, Ludvigsen TC, Drogset JO, Grontvedt T, Solheim E, Strand T, Roberts S, Isaksen V, Johansen O. Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am. 2004 Mar;86(3):455-64. doi: 10.2106/00004623-200403000-00001. PubMed 14996869 ↗
  • Rosenzweig A. Cardiac cell therapy--mixed results from mixed cells. N Engl J Med. 2006 Sep 21;355(12):1274-7. doi: 10.1056/NEJMe068172. No abstract available. PubMed 16990391 ↗
  • Saris DB, Vanlauwe J, Victor J, Haspl M, Bohnsack M, Fortems Y, Vandekerckhove B, Almqvist KF, Claes T, Handelberg F, Lagae K, van der Bauwhede J, Vandenneucker H, Yang KG, Jelic M, Verdonk R, Veulemans N, Bellemans J, Luyten FP. Characterized chondrocyte implantation results in better structural repair when treating symptomatic cartilage defects of the knee in a randomized controlled trial versus microfracture. Am J Sports Med. 2008 Feb;36(2):235-46. doi: 10.1177/0363546507311095. PubMed 18202295 ↗
  • Saris DB, Vanlauwe J, Victor J, Almqvist KF, Verdonk R, Bellemans J, Luyten FP; TIG/ACT/01/2000&EXT Study Group. Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med. 2009 Nov;37 Suppl 1:10S-19S. doi: 10.1177/0363546509350694. Epub 2009 Oct 21. PubMed 19846694 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 26, 2011, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00414700
Lead sponsor
TiGenix n.v.
Responsible party
Sponsor
First posted
Dec 22, 2006
Start date
Feb 2002
Primary completion
Jul 2006
Completion
Jan 2010
Results posted
Jan 18, 2010
Last update
Sep 26, 2011

Study contacts

Daniël BF Saris, M.D., Ph.D.
principal investigator · University Medical Center Utrecht, Department of Orthopedics, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Johan Vanlauwe, M.D.
principal investigator · University Hospitals Leuven, Department of Orthopedics, Herestraat 49, 3000 Leuven, Weligerveld 1, 3212 Pellenberg, Belgium.
Frank P Luyten, M.D., Ph.D.
study director · Division of Rheumatology, Department of Muskuloskeletal Sciences, University Hospitals, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium

Oversight

Data monitoring committee
No
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