Multicenter Orthopaedic Outcome Network Early Anti-inflammatory Treatment in Patients with Acute ACL Tear” (MOON-AAA) Clinical Trial

OBJECTIVES: We present the early results from the “Multicenter Orthopaedic Outcome Network Early Anti-inflammatory Treatment in Patients with Acute ACL Tear and Painful Effusions” (MOON-AAA) clinical trial (figure 1). This trial allows for a well controlled prospective cohort of patients with isolated ACL injury at risk for OA. We compared the effect of a single versus a repeated dosage of Kenalog within the first two weeks after ACL injury and its effect on chondral degradation in the first 4 weeks prior to surgical reconstruction of the ACL. METHODS: 49 patients with isolated ACL tears were enrolled. Knee joints were aspirated and patients received an injection with 40 mg Kenalog either within 4 days, 10 days, both time points or not at all (saline injection control). Serum, synovial fluid and urine were collected at 3 time points. Permutated block randomization, triple blinding, independent monitoring and standardized x-ray was performed to comply with GCP standards. Patient reported outcomes were collected at 6 time points up to 6 months post-ACL reconstruction(IKDC, KOOS and Marx activity level). A standardized synovial fluid biomarker panel was analyzed according to OARSI guidelines. Statistical analysis were performed using SAS mixed models analysis. RESULTS: Serum analysis shows significant change after injury. Chondrodegradatory markers such as CTX-II, MMP-1 and MMP-3 as well as COMP indicate a progressive destruction of chondral matrix and collagen breakdown . There is a dramatic (250%) increase of CTX-II in the first 4 weeks. Matrix proteins such as MMP-1 and 3 as well as COMP show an initial increase and then a steep decline (see figure 1). Inflammatory markers (IL-1 alpha, IL-1beta, IRAP) show a decline from the time of injury. IL-1 alpha, however shows a dramatic uptake after week 2. This longitudinal data confirms a dramatic onset of early osteoarthritic biomarker profiles immediately after ACL injury as measured in synovial fluid.The administration of 40 mg of Kenalog significantly changes this dynamic. CTX-II shows a dramatic reduction and stays close to baseline levels over the course of 4 weeks pre-operatively. COMP and MMP-1 show a significantly lesser decline.There is no significant difference in the effect of Kenalog if given within 4 days of injury or within 2 weeks. There is a statistical trend indicating that a repeated dose of Kenalog may be more efficient in normalizing the biomarker levels. No AE’s, infections were observed. Two of 49 patients suffered a retear at 6 months upon return to activities. CONCLUSION: Our data show that posttraumatic osteoarthritis begins at the time of injury and results early on in dramatic matrix changes in the knee joint. An early intervention with an antiinflammatory agent, such as Kenalog, maybe be able to prevent some of these changes observed.We do not currently know if the early intervention results in meaningful clinical differences in overall outcome. Further follow-up will answer this question. However, it is encouraging that a simple early intervention is able to affect early chondral degeneration. Should the early intervention with Kenalog lead to meaningful changes in outcome at 2 or 6 years the current treatment paradigm for ACL injured patients may have to be changed.