A Randomized Controlled Trial Comparing Chondro-Gide® to Microfracture Alone for Treatment of Knee Cartilage Defects.

Randomised Multi-Center Study: Microfracturing With Chondro-Gide® for the Treatment of Isolated Cartilage Defects in the Knee Project-Nr.: 10830-003

The purpose of this study is to evaluate the safety and effectiveness of using Chondro-Gide® collagen membrane either sutured or glued compared to microfracture alone in the treatment of symptomatic cartilage defects of the knee.

Study Overview

• Status: Completed
• Conditions: Cartilage Injury; Osteochondritis Dissecans
• Intervention / Treatment: Procedure: Microfracture; Device: Chondro-Gide sutured; Device: Chondro-Gide glued

Detailed Description

• Prospective, randomized, active treatment-controlled, open-label multicenter study (up to 40 sites in the US and EU).
• All subjects that meet preoperative screening eligibility criteria will be randomized to treatment with Chondro-Gide® either sutured or glued or Microfracture alone.
• Eligible and consenting subjects are randomized in a 1:1:1 ratio using centralized randomization list to receive one of the following treatments: Group I: Microfracture alone; Group II: Microfracture covered with a Chondro-Gide® membrane glued with fibrin glue (AMIC glued); Group III: Microfracture covered with a Chondro-Gide® membrane sutured (AMIC sutured)
• All subjects will be assessed at intervals post-procedure (6 weeks, 3 months, and 1,2 and 5 years).
• Subjects will be required to follow a strict pre-specified post-surgery rehabilitation protocol specific to the defect location.
• Measures to assess effectiveness and safety will be conducted at all follow-ups.
• Safety will be assessed by the collection of adverse events at all timepoints.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Bad Abbach, Germany
    • University of Regensburg
  • Freiburg, Germany
    • Universitatsklinikum Freiburg
  • Giessen, Germany
    • Universitätsklinikum Gießen
  • Hamburg, Germany
    • Orthopedikum Hamburg
  • Hanover, Germany
    • Unfallklinik Hannover
  • Lubeck, Germany
    • University of Schleswig-Holstein
  • Ravensburg, Germany
    • Sportklinik Ravensburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female between 18 and 50
• One or two cartilage defects Grade III or IV according to Outerbridge classification
• Defect size between 2 and 10 cm2 (inclusive)
• Intact normal surrounding cartilage to suture the Chondro-Gide® membrane
• Informed consent
• Patient willing to fulfill a strict postoperative physiotherapy scheme

Exclusion Criteria:

• More than 2 defects
• Defects on both knees
• X-ray signs of osteoarthritis
• Bone lesion > 0.7 cm in the defect
• Knee instability, varus or valgus deformation, status after complete meniscus resection, status after mosaicplasty, patella dysplasia
• Rheumatoid, infectious disease
• Skin lesion on the operated knee
• Treatment with cartilage building medication
• Drug and alcohol abuse
• Chronic heart disease, endocrine or metabolic disease, Haemophilia A/B
• Pregnancy or lactation
• Collagen allergy
• Participation in other Trials

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: microfracture; Microfracture is an arthroscopic surgical technique involving placement of microfracture penetrations within the cartilage defect to provide stem cells and growth factors from the bone marrow to aid cartilage repair	Procedure: Microfracture; Microfracture is a well-established arthroscopic surgical technique for cartilage repair which involves several systematic steps, including debridement to a stable cartilage margin, careful removal of the calcified cartilage layer, and homogeneous placement of microfracture penetrations within the cartilage defect, with resultant complete defect fill by a well-anchored clot
Experimental: Microfracture with Chondro-Gide sutured; Microfracture covered with a collagen membrane (Chondro-Gide®) using atraumatic sutures in a one-step mini-arthrotomy procedure	Device: Chondro-Gide sutured; Implantation of Chondro-Gide membrane using atraumatic sutures following microfracture via mini-arthrotomy
Experimental: Microfracture with Chondro-Gide glued; Microfracture covered with a collagen membrane (Chondro-Gide®) using fibrin glue in a one-step mini-arthrotomy procedure	Device: Chondro-Gide glued; Implantation of Chondro-Gide membrane using Fibrin glue following microfracture via mini-arthrotomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histological evaluation of structural repair of evaluable biopsies harvested from the core of the index lesion during arthroscopy at 2 years	The macroscopically assessed integration, surface properties and extent of filling of the defect and the microscopically assessed using the International Cartilage Repair Society (ICRS) score	2 years post-surgery
MRI (magnetic resonance imaging) assessment of structural repair parameters.	Structural repair is assessed with magnetic resonance imaging (MRI, 1.5T) by an independent and blinded radiologist, with a focus on the extent, signal intensity and surface of the defect filling, integration to adjacent cartilage, and bone marrow lesion (BML).	6 months and 1,2 and 5 years post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in the patient's evaluation of overall knee condition using the Modified Cincinnati Knee Rating System.	The Change from Baseline will be evaluated.	6 months and 1,2 and 5 years post-surgery
Change from Baseline in the patient's evaluation of pain using the Visual Analog Scale (VAS).	The Change from Baseline will be evaluated.	6 months and 1,2 and 5 years post-surgery
Change from Baseline in the patient's evaluation of overall knee condition using the International Cartilage Repair Society (ICRS) "Cartilage Injury Evaluation Package".	The Change from Baseline will be evaluated.	6 months and 1,2 and 5 years post-surgery
Adverse Events (AE) Review	The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE), will be collected for all participants.	5 years post-surgery

Collaborators and Investigators

• Sponsor: Geistlich Pharma AG
• Investigators: Principal Investigator: Sven Anders, MD, University of Regensburg

Publications and helpful links

General Publications

• Anders S, Volz M, Frick H, Gellissen J. A Randomized, Controlled Trial Comparing Autologous Matrix-Induced Chondrogenesis (AMIC(R)) to Microfracture: Analysis of 1- and 2-Year Follow-Up Data of 2 Centers. Open Orthop J. 2013 May 3;7():133-43. doi: 10.2174/1874325001307010133. Print 2013.
• Volz M, Schaumburger J, Frick H, Grifka J, Anders S. A randomized controlled trial demonstrating sustained benefit of Autologous Matrix-Induced Chondrogenesis over microfracture at five years. Int Orthop. 2017 Apr;41(4):797-804. doi: 10.1007/s00264-016-3391-0. Epub 2017 Jan 20.

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: December 2, 2016
• First Submitted That Met QC Criteria: December 12, 2016
• First Posted (Estimate): December 15, 2016

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: February 20, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: knee surgery; microfracture; enhanced marrow stimulation; articular cartilage; Autologous Matrix-Induced Chondrogenesis; Chondro-Gide®; AMIC
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Cartilage Diseases; Osteochondritis; Osteochondritis Dissecans
• Other Study ID Numbers: 10830-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No