ACI-C Versus AMIC. A Randomized Trial Comparing Two Methods for Repair of Cartilage Defects in the Knee

A Randomized Trial Comparing Autologous Chondrocyte Implantation Using Collagen Membrane (ACI-C) Versus (Autologous Matrix Induced Chondrogenesis) AMIC for Repair of Cartilage Defects in the Knee

ACI-C versus AMIC: A controlled randomized trial comparing Autologous Chondrocyte Implantation ( ACI) and Autologous Matrix Induced Chondrogenesis (AMIC) for repair of cartilage defects in the knee.

Eighty patients (Forty in each group) having symptomatic cartilage defects in their knee are planned to include in this study.

Both techniques will use the ChondroGide membrane from Geistlich to cover the defects. ACI includes an arthroscopy to harvest cartilage for cell cultivation in our lab located in Tromso. 3-4 weeks later using a mini arthrotomy the cells will be implanted under the ChondroGide membrane.

The AMIC group will be listed for a mini arthrotomy, cleaning of the defect, microfracture and cover of the defect using the same ChondroGide membrane.

In both groups stitches and fibrin glue will be used to fix the membrane.

Inclusion criteria:

Age between 18-60, Informed consent signed by patient, Symptomatic cartilage defect. Size more than 2 square cm.

Exclusion criteria Alcohol or drug abuse during the last three years, Inflammatory joint disease, Serious illness

Preoperative examination and follow up: Clinical examination and registration of KOOS (a validated knee score), VAS (visual analog pain scale) and Lysholm knee score. Radiographs of the involved knee including weightbearing standing radiographs of both knees. Kellgren- Lawrence classification will be used for grading of OA.

Patients will be checked after 1, 2, 5 and 10 years following surgery. Symptomatic patients having a new cartilage resurfacing operation or prosthesis will be listed as failures of the initial treatment.

Hypothesis: AMIC will be equal to ACI, and if that is the case this would be a benefit for the patients and the society. AMIC is much cheaper compared to ACI (needing an expensive cell cultivation and two surgeries).

Data will be analyzed using the SPSS statistical package.

Study Overview

• Status: Active, not recruiting
• Conditions: Osteoarthritis; Osteonecrosis; Cartilage Injury; Osteochondritis Dissecans
• Intervention / Treatment: Procedure: Treatment of cartilage defects in the knee

Detailed Description

Please see referenced articles (1-3) for details regarding ACI and AMIC

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Troms
    • Tromso, Troms, Norway, 9038
      • University Hospital of North Norway

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age between 18-60 yrs
• informed consent signed by patient
• symptomatic cartilage defect in the knee > 2 square cm

Exclusion Criteria:

• alcohol or drug abuse during the last three yrs
• inflammatory joint disease
• serious illness

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ACI-C; Autologous chondrocyte implantation using collagen membrane (ChondroGide) Please see reference 1 and 2 for details regarding ACI. In this study we are using the collagen membrane instead of periosteum- the other details are exactly the same as in our previous RCT.	Procedure: Treatment of cartilage defects in the knee; Two groups, either ACI or AMIC. ACI includes an arthroscopy for harvesting of cartilage 3-4 weeks prior to the open cartilage surgery. AMIC includes only open surgery at one setting.; Other Names: Autologous chondrocyte implantation; Autologous matrix induced chondrogenesis
Active Comparator: AMIC; Autologous matrix induced chondrogenesis. Microfracture of the defect and covering using the collagen membrane (ChondroGide). Please see reference 3 for details regarding AMIC	Procedure: Treatment of cartilage defects in the knee; Two groups, either ACI or AMIC. ACI includes an arthroscopy for harvesting of cartilage 3-4 weeks prior to the open cartilage surgery. AMIC includes only open surgery at one setting.; Other Names: Autologous chondrocyte implantation; Autologous matrix induced chondrogenesis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison Between the Two Groups of Mean Change From Baseline in Knee Injury and Osteoarthritis Outcome Score Total (KOOS) at Two Years.	KOOS is a knee-specific instrument, developed to assess the patients opinion about their knee and associated problems. It holds 42 items in 5 sub-scales (pain, other symptoms, function in daily living, function in sport and recreation and knee-related quality of life). The questionnaire yields a total score ranging from 0-100. A higher score indicates better knee function. The reported number is the mean change in KOOS total score from baseline after two years for each group. A positive number represents an improved knee function score.	2-years follow-up.
Comparison Between the Two Groups of Mean Change From Baseline in Knee Injury and Osteoarthritis Outcome Score Total (KOOS) at Five Years.	KOOS is a knee-specific instrument, developed to assess the patients opinion about their knee and associated problems. It holds 42 items in 5 sub-scales (pain, other symptoms, function in daily living, function in sport and recreation and knee-related quality of life). The questionnaire yields a total score ranging from 0-100. A higher score indicates better knee function. The reported number is the mean change in KOOS total score from baseline after two years for each group. A positive number represents an improved knee function score.	5-years follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison Between the Two Groups of Mean Change From Baseline in Lysholm Score at Two Years.	The Lysholm score is a scoring system for evaluating knee specific symptoms ranging from 0-100. Higher number indicates better knee function. The reported number is the mean change from baseline after two years for each group.	2-years follow-up.
Comparison Between the Two Groups of Mean Change From Baseline in a Visual Analogue Scale (VAS) Pain Score at Two Years.	The VAS scores describes the patients pain on a scale (0-100). Lower numbers, means less pain. The reported number is the mean change from baseline after two years for each group. Higher numbers represent more relief of pain.	2-years follow-up.
Failure	Treatment failures were reported as either a "hard failure" or a "clinical failure." A hard failure was defined as the patients needing a new resurfacing procedure of the index lesion or implantation of a knee prosthesis. A clinical failure was defined as any deterioration in KOOS scores at 2-year follow-up compared to baseline. Diagnostic re-arthroscopy or arthroscopy with debridement of synovia or the defect was not considered a failure. Sum of "hard" and "clinical" failures at two years in each group are reported.	2-years follow-up
Comparison Between the Two Groups of Mean Change From Baseline in Lysholm Score at Five Years.	The Lysholm score is a scoring system for evaluating knee specific symptoms ranging from 0-100. Higher number indicates better knee function. The reported number is the mean change from baseline after five years for each group.	Five-year follow-up
Comparison Between the Two Groups of Mean Change From Baseline in a Visual Analogue Scale (VAS) Pain Score at Five Years	The VAS scores describes the patients pain on a scale (0-100). Lower numbers, means less pain. The reported number is the mean change from baseline after two years for each group. Higher numbers represent more relief of pain.	Five-years follow-up.
Failure	Treatment failures were reported as either a "hard failure" or a "clinical failure." A hard failure was defined as the patients needing a new resurfacing procedure of the index lesion or implantation of a knee prosthesis. A clinical failure was defined as any deterioration in KOOS scores at 5-year follow-up compared to baseline. Diagnostic re-arthroscopy or arthroscopy with debridement of synovia or the defect was not considered a failure. Sum of "hard" and "clinical" failures at two years in each group are reported.	5-years follow-up
Kellgren-Lawrence Baseline vs 5-years in Each Group	Standing X-ray Rosenberg view of the knee obtained at baseline and 5-years follow up. X-rays were evaluated using the Kellgren-Lawrence scale by an independent orthopaedic surgeon.	5-year follow-up

Collaborators and Investigators

• Sponsor: University Hospital of North Norway
• Collaborators: University of Tromso
• Investigators: Principal Investigator: Gunnar Knutsen, MD, PhD, University Hospital of North Norway; Study Director: Ann Kristin Hansen, MD, PhD, University Hospital of North Norway

Publications and helpful links

General Publications

• Knutsen G, Drogset JO, Engebretsen L, Grontvedt T, Isaksen V, Ludvigsen TC, Roberts S, Solheim E, Strand T, Johansen O. A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am. 2007 Oct;89(10):2105-12. doi: 10.2106/JBJS.G.00003.
• 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.
• Benthien JP, Behrens P. The treatment of chondral and osteochondral defects of the knee with autologous matrix-induced chondrogenesis (AMIC): method description and recent developments. Knee Surg Sports Traumatol Arthrosc. 2011 Aug;19(8):1316-9. doi: 10.1007/s00167-010-1356-1. Epub 2011 Jan 14.
• Fossum V, Hansen AK, Wilsgaard T, Knutsen G. Collagen-Covered Autologous Chondrocyte Implantation Versus Autologous Matrix-Induced Chondrogenesis: A Randomized Trial Comparing 2 Methods for Repair of Cartilage Defects of the Knee. Orthop J Sports Med. 2019 Sep 17;7(9):2325967119868212. doi: 10.1177/2325967119868212. eCollection 2019 Sep.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2011
• Primary Completion (Actual): December 15, 2016
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: October 17, 2011
• First Submitted That Met QC Criteria: October 24, 2011
• First Posted (Estimated): October 25, 2011

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Cartilage repair; Chondrocytes; Stemcells
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Pathologic Processes; Connective Tissue Diseases; Necrosis; Cartilage Diseases; Osteochondritis; Osteochondritis Dissecans; Osteonecrosis
• Other Study ID Numbers: 2011/1159-3