Overview
This prospective, randomized study at Severance Hospital compares two subchondral drilling techniques during CARTISTEM implantation for symptomatic medial-compartment knee articular cartilage defects. Sixty participants will be allocated 1:1 to drilling with a 2-mm drill alone or sequential drilling with 4-mm and 2-mm drills. CARTISTEM preparation and implantation will be the same in both groups. High tibial osteotomy may be performed when needed to correct alignment.
The primary endpoint is the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation score at 12 months after surgery. The study will assess non-inferiority of the 2-mm technique using a prespecified margin of 10.3 points. Secondary assessments include pain and knee function, MRI cartilage repair and subchondral bone findings, radiographic osteoarthritis and alignment, and second-look arthroscopy in participants undergoing plate removal after high tibial osteotomy.
Description
Eligible adults with persistent knee pain and medial-compartment cartilage defects scheduled for CARTISTEM implantation will be recruited at the Department of Orthopedic Surgery, Severance Hospital. Computer-generated randomization will allocate 60 participants equally between two parallel groups. Recruitment is planned for one year, follow-up for 12 months after surgery, and the overall research period for three years after approval.
The experimental group will undergo subchondral drilling with a 2-mm drill alone. The active comparator group will undergo sequential drilling with 4-mm and 2-mm drills. Both groups will receive allogeneic human umbilical cord blood-derived mesenchymal stem cells mixed with sodium hyaluronate hydrogel and implanted into the drilled holes and over the cartilage defect. High tibial osteotomy may accompany implantation when clinically indicated.
Baseline assessments include demographics, clinical scores, standing knee radiographs, lower-limb alignment radiographs, and MRI. Arthroscopy at surgery will document lesion location, size, and ICRS lesion grade. IKDC, pain VAS, Lysholm, and KOOS assessments are scheduled at 3, 6, and 12 months. Radiographic assessments are scheduled at 6 and 12 months, and MRI at 12 months. Second-look arthroscopy is limited to participants undergoing plate removal after concomitant high tibial osteotomy.
Non-inferiority will be assessed using the between-group difference in the 12-month IKDC score and its 95% confidence interval, with a 10.3-point margin. Adverse events will be assessed at postoperative visits.
Participants are masked to the allocated drilling technique. Assessors of secondary imaging, arthroscopic, and histological outcomes are masked to allocation and evaluate coded participant information. The operating surgeon is aware of allocation. No biopsy or genetic analysis is planned.
Research funding: MEDIPOST; total study budget: KRW 60,000,000.
Eligibility
Inclusion Criteria:
- Age 19 years or older.
- Knee pain for at least 3 months despite conservative treatment, including medication or physical therapy.
- Medial-compartment knee arthritis or articular cartilage defects judged to be the main cause of symptoms.
- Imaging-confirmed medial-compartment cartilage defects for which CARTISTEM implantation has been decided.
- Voluntary written informed consent by the participant or legally authorized representative after understanding the study.
Exclusion Criteria:
- Surgery for knee cartilage injury within 1 year before screening.
- Ligament instability requiring simultaneous ligament surgery.
- Kellgren-Lawrence grade IV osteoarthritis on weight-bearing anteroposterior knee radiographs.
- Mechanical-axis varus deformity of 5 degrees or greater, unless corrected by simultaneous high tibial osteotomy.
- Autoimmune or inflammatory arthritis, including rheumatoid arthritis.
- Inability to undergo MRI.
- Body mass index of 35 kg/m² or greater.
- Inability to adequately understand the study explanation, including illiteracy or a language barrier.
- Age younger than 19 years.
