Cartilage Injury, Osteoarthritis, Osteochondritis Dissecans, Osteonecrosis
Conditions
Keywords
Cartilage repair, Chondrocytes, Stemcells
Brief summary
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.
Detailed description
Please see referenced articles (1-3) for details regarding ACI and AMIC
Interventions
PROCEDURETreatment 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.
Sponsors
University of Tromso
University Hospital of North Norway
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
RCT, Two arms ACI-C and AMIC
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison Between the Two Groups of Mean Change From Baseline in Knee Injury and Osteoarthritis Outcome Score Total (KOOS) at Two Years. | 2-years follow-up. | 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. |
| Comparison Between the Two Groups of Mean Change From Baseline in Knee Injury and Osteoarthritis Outcome Score Total (KOOS) at Five Years. | 5-years follow-up | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Failure | 2-years follow-up | 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. |
| Comparison Between the Two Groups of Mean Change From Baseline in Lysholm Score at Five Years. | Five-year follow-up | 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. |
| Comparison Between the Two Groups of Mean Change From Baseline in Lysholm Score at Two Years. | 2-years follow-up. | 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. |
| Kellgren-Lawrence Baseline vs 5-years in Each Group | 5-year follow-up | 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. |
| Comparison Between the Two Groups of Mean Change From Baseline in a Visual Analogue Scale (VAS) Pain Score at Five Years | Five-years follow-up. | 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. |
| Comparison Between the Two Groups of Mean Change From Baseline in a Visual Analogue Scale (VAS) Pain Score at Two Years. | 2-years follow-up. | 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. |
Countries
Norway
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 21 |
| AMIC Autologous matrix induced chondrogenesis. Microfracture of the defect and covering using the collagen membrane (ChondroGide).
Please see reference 3 for details regarding AMIC
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. | 20 |
| Total | 41 |
Baseline characteristics
| Characteristic | AMIC | Total | ACI-C |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 41 Participants | 21 Participants |
| Age, Continuous | 38 years STANDARD_DEVIATION 8.2 | 37.5 years STANDARD_DEVIATION 9.1 | 37 years STANDARD_DEVIATION 10.8 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Norway | 20 participants | 41 participants | 21 participants |
| Sex: Female, Male Female | 12 Participants | 19 Participants | 7 Participants |
| Sex: Female, Male Male | 8 Participants | 22 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 20 |
| other Total, other adverse events | 3 / 21 | 3 / 20 |
| serious Total, serious adverse events | 0 / 21 | 0 / 20 |
Outcome results
Primary
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.
Time frame: 5-years follow-up
Primary
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.
Time frame: 2-years follow-up.
Population: Comparison between groups were performed on the intention-to-treat population (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACI-C | Comparison Between the Two Groups of Mean Change From Baseline in Knee Injury and Osteoarthritis Outcome Score Total (KOOS) at Two Years. | 10.3 score on a scale | Standard Deviation 16 |
| AMIC | Comparison Between the Two Groups of Mean Change From Baseline in Knee Injury and Osteoarthritis Outcome Score Total (KOOS) at Two Years. | 18.1 score on a scale | Standard Deviation 19.4 |
Secondary
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.
Time frame: Five-years follow-up.
Secondary
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.
Time frame: 2-years follow-up.
Population: Intention to treat population (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACI-C | Comparison Between the Two Groups of Mean Change From Baseline in a Visual Analogue Scale (VAS) Pain Score at Two Years. | 19.6 units on a scale | Standard Deviation 25.9 |
| AMIC | Comparison Between the Two Groups of Mean Change From Baseline in a Visual Analogue Scale (VAS) Pain Score at Two Years. | 30.6 units on a scale | Standard Deviation 26 |
Secondary
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.
Time frame: Five-year follow-up
Secondary
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.
Time frame: 2-years follow-up.
Population: Comparison between groups were performed on the intention-to-treat population (ITT).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ACI-C | Comparison Between the Two Groups of Mean Change From Baseline in Lysholm Score at Two Years. | 17.0 score on a scale | Standard Deviation 14.9 |
| AMIC | Comparison Between the Two Groups of Mean Change From Baseline in Lysholm Score at Two Years. | 19.7 score on a scale | Standard Deviation 22.9 |
Secondary
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.
Time frame: 2-years follow-up
Population: Intention to treat population (ITT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ACI-C | Failure | 3 Participants |
| AMIC | Failure | 5 Participants |
Secondary
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.
Time frame: 5-years follow-up
Secondary
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.
Time frame: 5-year follow-up