Clinical trial NCT02981355: Randomized Evaluation of BST-CarGel Versus Microfracture Alone On Recovery From Distal Femoral Cartilage Lesions
Official title: Randomized Evaluation of BST-CarGel Versus Microfracture Alone On Recovery From Distal Femoral Cartilage Lesions
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Traumatic; Lesion
Degenerative Lesion of Articular Cartilage of Knee
Keywords: BST-CarGel
Microfracture
Cartilage Lesion, Chondral Lesion
Femoral condyle
Bone Marrow Stimulation
Cartilage Repair
Tear of Articular Cartilage of Knee, Current
Lead sponsor: Piramal Healthcare Canada Ltd
Sponsor class: INDUSTRY
Collaborators: name: Smith & Nephew, Inc.
name: Global Research Solutions
First posted: 2016-12-05
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This multi-centre randomized, controlled trial will assess the impact of BST-CarGel scaffold with microfracture versus microfracture alone on short and long term clinical benefit in patients with cartilage lesions of the femoral condyle requiring operative management.

Detailed description: The current standard of treatment for cartilage lesions on the femoral condyle is microfracture, which is conducted by penetrating the subchondral bone below the lesion. This procedure creates a natural healing response as a result of the bleeding and clotting caused by the microfracture, restoring the lesion. BST-CarGel (Piramal Life Sciences, Bio-Orthopaedic Division), a liquid chitosan-containing polymer scaffolding, has been developed as an intra-articular injectable scaffold to aid in the stabilization of the blood clot created by microfracture. BST-CarGel does not interfere with the normal clotting process; however, it enables a prolonged healing time due to the increased stabilization of the clot within the lesion and the inhibition of clot retraction.

The RECORD trial is a multi-centre, randomized, controlled trial to assess the impact of the BST-CarGel scaffold and microfracture versus microfracture alone on short term clinical benefit as measured by loaded knee pain (single leg squat) on a visual analogue scale (3-6 months), mid-long term clinical benefit as measured by the same loaded knee pain (single leg squat) (9, 12, and 24 months) and Tegner Activity Score (TAS), International Knee Documentation Committee (IKDC), and Knee Injury and Osteoarthritis (KOOS) at 3, 6, 9, 12 and 24 months post-operatively. Approximately 158 participants with full-thickness grade III and IV cartilage lesions will be randomised in a 1:1 ratio to receive one of the two treatments during an arthroscopic procedure and will be followed for up to 24 months to collect outcomes.

Eligibility criteria: Inclusion Criteria:

* requires cartilage repair treatment due to distal femoral cartilage lesion
* is 18-55 years of age at the time of surgery
* has single, focal cartilage lesion on one of the femoral condyles
* has symptomatic cartilage lesion that has failed conservative management
* has a single lesion classified as focal, full-thickness grade 3 or 4 according to the ICRS (3A, 3B, 3C, 3D and 4A)
* an area of lesion between 1.5-3 cm2 after debridement
* has a stable knee (\<5-mm side-to-side difference on Lachman and varus and valgus stress testing and grade 0 or 1 on the pivot-shift test) and an intact meniscal rim
* is willing and able to participate in required follow-up visits at the investigational site and to complete study procedures and questionnaires and recommended physiotherapy regimen
* has agreed to discontinue the use of all knee pain medication 3 days before the pre-treatment visit and the post-treatment follow-up visits at 3, 6, 9, 12, and 24 months
* has consented to participating in the study by signing the IRB/EC approved informed consent form
* no deep osteochondral defect ( \< 5 mm bone loss)

Exclusion Criteria:

* has multiple lesions or kissing (opposing) lesion(s) greater than GII
* has clinically relevant compartment malalignment (\>5°)
* has bone cyst(s) associated with, or adjacent to, the index lesion
* has Osteochondritis Dissecans with bone or bone-cartilage fragment in place
* has had ligament treatments in the index knee within the previous 24 months
* has had surgical cartilage treatments in the index knee within previous 12 months
* has had intra-articular injections in the index knee within the previous 2 months
* has diagnosis of an immunosuppressive disorder
* has a BMI \> 30 kg/m2
* has concomitant healing bone fractures
* has a single lesion classified as focal, full-thickness grade 4B as defined by ICRS
* has noteworthy pain in the ipsilateral hip or ankle or contralateral hip, knee, or ankle
* has inflammatory arthropathy
* has blood clotting disorders, was receiving anticoagulant therapy, or has recurring deep vein thrombosis
* has a serious heart condition or liver and/or renal abnormalities diagnosed within the previous 24 months
* has chronic infection of the lower joint extremities
* has a history of alcohol or drug abuse within the previous 12 months
* is facing current or impending incarceration
* has a known allergy to shellfish
* is pregnant or plans to become pregnant during the course of the study
* in the opinion of the PI, has an emotional or neurological condition that would pre-empt their ability or willingness to participate in the study including mental illness, drug or alcohol abuse
* chronic knee pain
* has a documented medical history of vitamin-D deficiency that is not being managed with supplementation
* is entered in another investigational drug, biologic, or device study or has been treated with an investigational product in the past 30 days
* requires an open procedure
* is known to be at risk for lost to follow-up, or failure to return for scheduled visits

Primary outcomes:
measure: Change in loaded knee pain (single leg squat) visual analogue scale (VAS)
timeFrame: Baseline to 24 months post-surgery
measure: Change in knee function measured by the TAS questionnaire
timeFrame: Baseline to 24 months post-surgery
measure: Change in knee function measured by the IKDC questionnaire
timeFrame: Baseline to 24 months post-surgery
measure: Change in knee function measured by the KOOS questionnaire
timeFrame: Baseline to 24 months post-surgery
Secondary outcomes:
measure: Repair tissue quantity and quality
timeFrame: Up to 24 months post-surgery
measure: Adverse events related to treatment
timeFrame: Up to 24 months post-surgery
measure: Economic evaluation
timeFrame: surgical visit, 2 weeks, 6 weeks, 3 months, 6 months, 9 months,12 months and 24 months post-surgery
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Calvary Wakefield Hospital
city: Murdoch
country: Australia
facility: Murdoch Orthopaedic Clinic
city: Banff
country: Canada
facility: Banff Sport Medicine
city: London
country: Canada
facility: Fowler Kennedy Sport Medicine Clinic
city: Montreal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
city: Lyon
country: France
facility: Hopital de La Croix-Rousse
city: Nancy
country: France
facility: CHRU Nancy - Hospital Central
city: Regensburg
country: Germany
facility: University Medical Centre Regensburg
city: Barcelona
country: Spain
facility: Hospital Universitari del Mar
city: Barcelona
country: Spain
facility: Hospital Quironsalud Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Zurich
country: Switzerland
facility: SportClinic Zurich / Hirslanden Clinic
city: Birmingham
country: United Kingdom
facility: The Royal Orthopaedic Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
Study officials:
affiliation: Piramal Healthcare Canada Ltd
name: Jean-Pierre Desmarais
role: STUDY_CHAIR
References:
citation: Shive MS, Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, Desnoyers J, Methot S, Vehik K, Restrepo A. BST-CarGel(R) Treatment Maintains Cartilage Repair Superiority over Microfracture at 5 Years in a Multicenter Randomized Controlled Trial. Cartilage. 2015 Apr;6(2):62-72. doi: 10.1177/1947603514562064.
citation: Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, Desnoyers J, Restrepo A, Shive MS. Novel scaffold-based BST-CarGel treatment results in superior cartilage repair compared with microfracture in a randomized controlled trial. J Bone Joint Surg Am. 2013 Sep 18;95(18):1640-50. doi: 10.2106/JBJS.L.01345.