Follow-Up Study Evaluating The Long Term Safety and Efficacy of BST-CarGel and Microfracture Repair of the Knee

Follow-up Study Evaluating The Long-Term Safety and Efficacy of BST-CarGel® and Microfracture In Repair of Focal Articular Cartilage Lesions on The Femoral Condyle (Extension Study of Protocols CG-CIP01-P & CG-CIP02-P)

This follow-up study will evaluate the effects of BST-CarGel® application to a microfractured lesion (investigational) and microfracture alone (control) for up to 5 years from treatment in subjects, treated under Protocols CG-CIP01-P and CG-CIP02-P, and will serve as a post approval study for these Protocols, in support of a commercial application. The lesions treated under Protocols CG-CIP01-P and CG-CIP02-P were focal lesions of articular cartilage, grade 3 or 4 (either ICRS or Outerbridge classification) on the medial and lateral femoral condyles of the knee, and were classified as either acute or chronic.

Study Overview

• Status: Completed
• Conditions: Knee Injuries
• Intervention / Treatment: Device: Microfracture with BST-CarGel; Device: Microfracture without BST-CarGel

Detailed Description

Cartilage repair currently remains a problematic orthopedic concern with no effective solution. The development of new surgical techniques or therapies is critical in meeting this medical need.

Clinical data regarding the long-term durability of repair tissue resulting from cartilage repair techniques such as microfracture, autologous chondrocyte implantation or mosaicplasty is lacking. Only two studies, one comparative and one uncontrolled, have examined long-term repair outcomes (over 4 years). These studies reinforced the concept that further studies are needed to identify a technique or product that will lead to long-term clinical benefit through improved cartilage repair efficacy.

BST-CarGel® is a medical device derived from chitosan applied to a microfractured lesion and has been shown to promote the quantity and quality of cartilage repair tissue in animals. The efficacy and safety of BST-CarGel® is currently being evaluated in humans as compared to the standard of care treatment, microfracture, in a 12 month international study in Canada, Europe and Korea under Protocols CG-CIP01-P and CG-CIP02-P. When these protocols were designed and carried out, the BST-CarGel® technology belonged to BioSyntech Canada Inc. Afterwards, the technology was acquired by Piramal Healthcare (Canada) Ltd. which is now the owner of the technology and the sponsor for this Extension Study CG-C1P04.

This follow-up study will evaluate the long-term effects (5 yrs) of BST-CarGel® + microfracture and microfracture alone in subjects treated in the pivotal and sub-studies.

All eligible subjects (maximum 80) who were treated under Protocols CG-CIP01-P and CG-CIP02-P and completed the required 12 month follow-up period will be asked to participate in this follow-up study.

The stratification from Protocols CG-CIP01-P and CG-CIP02-P (investigational site and lesion type) will be retained for the purposes of the follow-up study, and all third parties such as the MRI central reading facility will remain blinded to the treatment received under Protocols CG-CIP01-P and CG-CIP02-P.

Comparisons between the two treatment groups will be performed.

The following assessments will be done annually at years 3 and/or 4 and 5 post -treatment under Protocols CG-CIP01-P and CG-CIP02-P in subjects treated with BST-CarGel + microfracture or microfracture alone:

1. Analyses of tissue repair will be carried out based on the degree of lesion filling and quality of repair tissue using MRI
2. The general health status of subjects will be captured in the case report form (CRF) and will include the subject's overall health status, treated knee status, adverse events (AEs) and concomitant medications.
3. The assessment of the subject's knee pain, stiffness, functional ability and quality of life through self-assessment questionnaires (Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and short-form-36 (SF-36v2)

• Study Type: Observational
• Enrollment (Actual): 67

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • University of Calgary Sports Medicine Centre
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W7
      • Simon Fraser Orthopaedic Fund, Royal Columbian Hospital
    • Vancouver, British Columbia, Canada, V6T 2B5
      • Joint Preservation Centre of British Columbia
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3M 3E4
      • Pan Am Clinic
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 4M2
      • Orthopaedic and Sport Medicine Clinic of Nova Scotia
  • Ontario
    • Oakville, Ontario, Canada, L6J 3L7
      • Oakville Trafalgar Memorial Hospital
    • Ottawa, Ontario, Canada, K1S 5B6
      • Sports Medicine Center, Carleton University
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre, Orthopaedics Research Office
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • Hospital Sacre-Coeur de Montreal
    • Québec, Quebec, Canada, G1J 1Z4
      • CHA-Pavillon Enfant-Jésus
    • Québec, Quebec, Canada, J4V 2H1
      • Hôpital Charles LeMoyne, Unité d'investigation non invasive
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial de Barcelona
  • Gijon, Spain
    • Cirugia Ortopedica y Traumatologia, Medicina del Deporte
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid
    • Majadahonda, Madrid, Spain
      • FREMAP Centro de Prevención y Rehabilitatión

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients that have been treated under either protocol CG-CIP01 or CG-CIP02

Description

Inclusion Criteria:

• The subject was treated under Protocol CG-CIP01 or CG-CIP02 and completed 12 month follow-up period
• The subject has understood and signed a Research Ethics Board(REB) approved Informed Consent Form (ICF)

Exclusion Criteria:

• The subject was not treated under Protocol CG-CIP01-P or CG-CIP02-P
• The subject did not complete 12 month follow-up period

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental; Microfracture with BST-CarGel	Device: Microfracture with BST-CarGel
Control; Microfracture without BST-CarGel	Device: Microfracture without BST-CarGel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Degree of Lesion Filling (%Fill) by Repair Tissue at Degree of Lesion Filling (%Fill) by Repair Tissue at 5 Years Through MRI.	Degree of lesion filling (repair tissue volume) as measured by quantitative MRI at 5 Years post-treatment compared to the debrided lesion 1-month post-treatment (baseline).	5 years
Repair Tissue Quality (T2 MRI)	Tissue quality of the repair tissue as measured by T2 MRI as an index for collagen-based structure.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline for Knee-related Pain, Stiffness and Function at 5 Years (WOMAC Parts A, B, C)	The three sub-scales: 1) Pain, 2.) stiffness and 3.) function scores ranged from 0-10. Pain had 5 items and stiffness had 2 items, and function had 17 items. The total score for pain ranged from 0 no pain to 50 worst pain. The total score for stiffness ranged from 0 no stiffness to 20 worst stiffness. The total score for function raged from 0 no function to 170 worst function. A higher score indicates a better health state improvement.	5 years
The Number of Participants With Adverse Events Until 5 Years	Safety was assessed by recording the number of participants with Adverse Events (AEs) and their severity from the time of ICF signing up to 5 years post-treatment.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Quality of Life Assessed Using the SF-36 Questionnaire.	SF-36 v2 includes 2 aggregate measures-Physical and Mental components-derived from 8 subscales. Least squares means are adjusted for baseline. Higher positive scores indicate better results. Scoring ranges from 0 to 100%.	1 and 5 years

Collaborators and Investigators

• Sponsor: Piramal Healthcare Canada Ltd
• Investigators: Principal Investigator: William Stanish, M.D, Orthopaedic and Sport Medicine - Dalhousie University

Publications and helpful links

General Publications

• 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.

Helpful Links

• Healthcare professionals please follow here - http://bst-cargel.piramal.com/content/medical-professional

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): March 1, 2014

Study Registration Dates

• First Submitted: November 22, 2010
• First Submitted That Met QC Criteria: November 22, 2010
• First Posted (ESTIMATE): November 24, 2010

Study Record Updates

• Last Update Posted (ACTUAL): January 24, 2018
• Last Update Submitted That Met QC Criteria: June 6, 2017
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Knee Pain; Knee; Cartilage; Arthroscopy; Chitosan; Cartilage repair; Scaffold; Microfracture; Chondrogenesis; Articular Cartilage Repair; Bone Marrow Stimulation
• Additional Relevant MeSH Terms: Fractures, Bone; Wounds and Injuries; Leg Injuries; Fractures, Stress; Knee Injuries
• Other Study ID Numbers: CG-CIP04-P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not planned