Clinical trial NCT01282034: Study for the Treatment of Knee Chondral and Osteochondral Lesions
Official title: Multicenter Randomized Controlled Trial for the Treatment of Knee Chondral and Osteochondral Lesions: Marrow Stimulation Techniques vs MaioRegen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Knee Chondral Lesion
Knee Osteochondral Lesion
Keywords: CHONDRAL
OSTEOCHONDRAL
Lead sponsor: Fin-Ceramica Faenza Spa
Sponsor class: INDUSTRY
First posted: 2011-01-24
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: INTRODUCTION Marrow stimulation techniques as subchondral drilling or microfractures represent ones of the most frequently used methods for chondral and osteochodral defects repair and considered as standard techniques.

MaioRegen® (Fin-Ceramica Faenza S.p.A., Italy) is a bioceramic, multi-layered scaffold, in a single gradient structure, consisting of deantigenated Type I equine collagen and Magnesium enriched-Hydroxyapatite, able to mime the entire osteocartilaginous section. MaioRegen® is able to promote the tissue regeneration in case of severe and large chondral/osteochondral lesions, otherwise difficult to treat, as previously demonstrated in vitro, in vivo and in a clinical study.

OBJECTIVES The present study proposes to compare MaioRegen® performances with respect to reference standard surgical techniques (microfractures and subchondral drilling) for the treatment of chondral/osteochondral lesions, in order to consolidate MaioRegen®, as innovative surgical approach.

STUDY DESIGN The clinical trial is multicenter, prospective, randomized, controlled, two-arm, single-blind and involves eleven European centres and 150 patients. Eligible subjects will be randomly allocated to one of the two treatment groups: control group, treated with marrow stimulation techniques, and treatment group, treated with MaioRegen® implant.

Patient defect will be evaluated pre-operatively and each patient enrolled must meet all the entry criteria for the trial. Before enrolment, each subject should declare his voluntary participation to the study by informed consent signature.

Arthroscopic control will be carried out immediately before the randomization and thus surgical treatment, to confirm the characteristics of the lesion to be treated and finalizing the recruitment.

For each patient 6, 12 and 24 months post-operative follow-up visits will be carried out and during each follow-up visit the Case Report Form (CRF) will be filled in the specific section.

Within the CRF, at each follow-up section, commonly used and specific scores will be assigned for the established end-points (IKDC, KOOS, Tegner Score, VAS, MRI Mocart Scoring System).

Patients selected will be randomized to undergo one of two study groups, as prescribed by the randomization list.

Detailed description: Post-operative MRI exams will be carried out for each patient during the follow-up visit, at 6, 12 and 24 months post-op., and centrally blind evaluated by two senior radiologists.

STATISTICS The study has been designed to demonstrate the superiority of MaioRegen® compared to marrow stimulation techniques.

On the basis of previous evidence and, assuming a minimum difference in the modification of the IKDC Subjective Knee Evaluation Score between MaioRegen® and the control therapy, the sample size was estimated in 74 patients for group (power=90%, first type error α=5%, drop-outs=10%), for a total sample size of 148 subjects.

The analysis of the primary end-point will be the evaluation of change from baseline to two years, in IKDC Subjective Knee Evaluation Score, comparing the results between the two groups.

Secondary end-points (functional improvement, quality of life improvement, tissue regeneration) will undergo the same analyses as the primary end-point, for each follow-up visit.

Frequency tables will be provided for overall judgement of the treatment. The incidence and gravity frequency of eventual events after surgery will be tabulated.

The study will be conducted after approval by the ethics committee board of each centre and possibly by the national competent authorities.

Eligibility criteria: Inclusion Criteria:

1. Patients provided written informed consent;
2. Patients aged between 18 and 60 years;
3. Knee symptomatic chondral lesion of grade III/IV (according to Outerbridge Classification) or osteochondral lesion;
4. Not re-fixable OCD lesions;
5. Lesion between 2-9 cm2;
6. Single lesion;
7. Patients agreed to actively participate in the rehabilitation protocol and follow-up program;
8. Male or female patients;
9. Women of childbearing age had to use a proven method to prevent pregnancy, before the surgical treatment.

Exclusion Criteria:

1. Patients incapable to understanding and will;
2. Patients participating in previous, concurrent or not, trials (ongoing or completed within 3 months);
3. Patients surgically treated for the same defect within one year;
4. Known allergy to collagen or calcium-phosphates;
5. Patients affected by malignancy;
6. Patients affected by metabolic or thyroid disorders;
7. Patients used to alcohol or drug (medication) abuse;
8. Patients affected by advanced osteoarthritis (Kellgren-Lawrence grade ≥3);
9. Patients affected by synovitis;
10. Untreated patellofemoral malalignment;
11. Varus or valgus malalignment exceeding 5°;
12. Body Mass Index \> 30;
13. Patients previously treated for total or partial meniscectomy (\>50% of the meniscus dimension);
14. Multiple lesions;
15. Kissing lesions;
16. Chondral/osteochondral tibial plate defects;
17. Concomitant menisci and chondral/osteochondral defects to be treated;
18. Untreated knee ligament instability.

Primary outcomes:
measure: IKDC Subjective Knee Evaluation Form-2000
timeFrame: two years
Secondary outcomes:
measure: IKDC Knee Examination Form-2000
timeFrame: six months and one year
measure: KOOS
timeFrame: six months, one year, two years
measure: Tegner score
timeFrame: six months, one year, two years
measure: VAS (Visual Analogue Scale) for pain evaluation
timeFrame: six months, one year, two years
measure: MRI exam and MOCART score
timeFrame: six months, one year, two years
Other outcomes:
Locations:
city: Wien
country: Austria
facility: AKH University Hospital
city: Ghent
country: Belgium
facility: Gent Univeristy Hospital
city: Freiburg im Breisgau
country: Germany
facility: University Medical Center
city: Negrar
country: Italy
facility: Ospedal Sacro Cuore Don Calabria
state: Verona
city: Bologna
country: Italy
facility: Istituti Ortopedici Rizzoli
city: Oslo
country: Norway
facility: Oslo University Hospital HF
city: Piekary Slaskie
country: Poland
facility: District hospital of orthopaedics
state: Katowice
city: CapeTown
country: South Africa
facility: Sport Science Orthopaedic Clinic
city: Kungsbacka
country: Sweden
facility: Kungsbacka Hospital
city: Zurich
country: Switzerland
facility: Schulthess Klinik
Study officials:
affiliation: Istituti Ortopedici Rizzoli
name: Maurilio Marcacci, Prof.
role: PRINCIPAL_INVESTIGATOR
References: