Clinical trial NCT02636881: Autologous Cartilage Implantation vs Arthroscopic Debridement
Official title: Focal Cartilage Defects in the Knee -A Randomized Controlled Trial Comparing Autologous Chondrocyte Implantation With Arthroscopic Debridement
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Knee Injury
Cartilage Injury
Lead sponsor: University Hospital, Akershus
Sponsor class: OTHER
First posted: 2015-12-22
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 82 patients aged 18-49 years with an isolated focal cartilage defect in the knee will be randomized to either receive autologous cartilage implantation or arthroscopic debridement. Both groups will then undergo a systematic physiotherapy training regime for 6-9 months. The Groups will then be compared for results, after 3, 6, 12 and 24 months, by using validated patient reported outcome scores (Lysholm, KOOS, Tegner) and EQ5D (European Quality of Life 5 dimensions) as well as clinical examination and radiological findings at 2 years (MRI).

Detailed description: Details Focal cartilage defects in the knee - A randomized controlled trial comparing Autologous Chondrocyte Implantation with arthroscopic debridement Clinical Compare the effect of Autologous Chondrocyte Implantation (ACI) with arthroscopic debridement (AD) in patients with symptomatic full thickness knee cartilage injuries larger than 2cm2.

Focal cartilage injuries in the knee might have devastating effect both in the short term and in the long term. Various surgical treatment options are available; with ACI established as a recognized treatment method for larger lesions. Meta-analysis and systematic reviews have required well-designed, long-term, multicenter studies to evaluate clinical outcomes of ACI with the use of a "no treatment" group as a control group.

H0: There is no difference in KOOS QoL after ACI or AD from baseline to 24 months after surgery.

H1: There is a difference in KOOS QoL after ACI or AD from baseline to 24 months after surgery.

Questionnaires: KOOS, Tegner score, Lysholm score, EQ-5D, VAS (Visual analogue scale).

Physical examination: range of motion and hop test. Radiology: x-ray and MRI of the knee. Primary aim: KOOS quality of life (QoL) subscore. Prospective, single-blinded parallel-group bicenter study with 2 treatment arms.

Approx. 36 months inclusion and 24 months follow up. In total 5 years. 24 months. All will be invited to participate in late controls after 5 and 10 years.

2 Norwegian hospitals: Akershus University Hospital and Oslo University Hospital - Ullevål.

82 patients Inclusion: age 18-50 years old, single symptomatic cartilage defect on femoral condyle or trochlea, defect size larger than 2 cm2, defect ICRS (International Cartilage Repair Society) grade 3-4, ligamentous stable knee, range of motion 5-105°, Lysholm score \< 75 and informed consent.

Exclusion: Osteoarthritis, rheumatoid or other systemic arthritis, malalignment \> 5° measured on x-rays, BMI \> 30, comorbidities that may influence surgery or rehabilitation, pregnancy, inability to complete questionnaires or rehabilitation, serious alcohol or drug abuse, previous cartilage surgery to the chondral defect except OCD (osteochondritis dissecans)surgery.

2 treatment groups with 41 patients in each group. 3 months (± 2 weeks), 6 months (± 4 weeks), 12 months (± 6 weeks) and 24 months (± 8 weeks). All will be invited to participate in late controls after 5 and 10 years.

If any unforeseen complication outside normal clinical practice occurs, the sponsor representative will be contacted as soon as possible with a parallel message to the local coordinators at the involved hospitals. During each follow up, there will be a case report form (CRF) regarding complications and safety.

A 5 mL venous blood sample will be drawn on the day of operation. The blood sample will be centrifuged before serum is pipetted in a sterile tube. The serum will be analyzed at Oslo University Hospital - Rikshospitalet on the cartilage biomarker microRNA-140 (miR-140).

During the open chondrocyte implantation the excess cartilage debrided from the rim of the lesion will be sent for similar microRNA-140 (miR-140) analysis. (applicable for the 41 patients in the ACI arm only) If normal distribution, aims will be analyzed using linear mixed models (LMM), and the primary aim will be performed as a post hoc test for the LMM, similar to performing a two-sample t-test. If no normal distribution, analysis will be performed using Mann-Whitney U-test.

Detecting a difference of 10 in primary aim with 80% power using a standard deviation of 15. A p \< 0,05 is statistically significant. This gives 37 patients in each group, adding 10% drop out meaning 41 patients in each group and 82 in total.

No interim analysis will be done. Monitor at Akershus University Hospital. Inclusion of 82 patients. The end of this study is 24 months after the last included patient. Inability to include 82 patients in 3 years. May prolong the inclusion period, or add other including hospitals in the study.

Eligibility criteria: Inclusion Criteria:

* Single symptomatic lesion of the trochlea, medial or lateral femoral condyle of the knee larger than 2 cm2.
* Cartilage lesion ICRS grade 3 or 4.
* More than 50 % of the menisci intact.
* Ligamentous stable knee
* Lysholm Score \< 75
* Acceptable range of motion (5-105 degrees)

Exclusion Criteria:

* Osteoarthritis
* Malalignment \> 5 degrees measured on HKA (hip-knee-ankle) radiographs
* Systemic arthritis
* Previous cartilage surgery
* Obesity BMI \> 30
* Serious drig or alcohol abuse
* Inability to answer questionnaires or partake in rehabilitation
* Comorbidity that may influence surgery or rehabilitation

Primary outcomes:
measure: The Knee Injury and Osteoarthritis Outcome Score (KOOS) Quality of Life
timeFrame: up to 24 months
Secondary outcomes:
measure: The Knee Injury and Osteoarthritis Outcome Score (KOOS) Other domains
timeFrame: preop, 3, 6, 12 and 24 months.
measure: Tegner Score
timeFrame: preop, 3, 6, 12 and 24 months.
measure: Lysholm Knee Score
timeFrame: preop, 3, 6, 12 and 24 months.
measure: EQ5D
timeFrame: preop, 3, 6, 12 and 24 months.
measure: Visual Analogue Scale
timeFrame: preop, 3, 6, 12 and 24 months.
measure: Range of motion
timeFrame: preop, 3, 6, 12 and 24 months.
measure: Magnetic Resonance Imaging
timeFrame: 24 months
measure: A Hop test
timeFrame: 24 months
Other outcomes:
Locations:
city: Lørenskog
country: Norway
facility: Akershus University Hospital
state: Oslo
Study officials:
affiliation: Research coordinator
name: Heidi Hanvold, PT
role: PRINCIPAL_INVESTIGATOR
affiliation: Akerhus University hospital
name: asbjørn Årøen, MD, PhD
role: STUDY_CHAIR
References:
citation: Randsborg PH, Brinchmann JE, Owesen C, Engebretsen L, Birkenes T, Hanvold HA, Benth JS, Aroen A. Autologous Chondrocyte Implantation Is Not Better Than Arthroscopic Debridement for the Treatment of Symptomatic Cartilage Lesions of the Knee: Two-Year Results From a Randomized-Controlled Trial. Arthrosc Sports Med Rehabil. 2024 Feb 16;6(2):100909. doi: 10.1016/j.asmr.2024.100909. eCollection 2024 Apr.
citation: Banitalebi H, Owesen C, Aroen A, Tran HT, Myklebust TA, Randsborg PH. Is T2 mapping reliable in evaluation of native and repair cartilage tissue of the knee? J Exp Orthop. 2021 Apr 28;8(1):34. doi: 10.1186/s40634-021-00350-1.
citation: Randsborg PH, Brinchmann J, Loken S, Hanvold HA, Aae TF, Aroen A. Focal cartilage defects in the knee - a randomized controlled trial comparing autologous chondrocyte implantation with arthroscopic debridement. BMC Musculoskelet Disord. 2016 Mar 8;17:117. doi: 10.1186/s12891-016-0969-z.