Abstract 48: Effect of Remote Ischemic Conditioning on Functional Outcomes in Patients With Supratentorial Intracerebral Hemorrhage: The Final Results of RICH-2 Randomized Controlled Clinical Trial

Introduction: Supratentorial intracerebral hemorrhage (ICH) is a devastating stroke subtype with high mortality and morbidity, and hematoma clearance is a critical therapeutic target. Remote ischemic conditioning (RIC) with transient ischemia and reperfusion applied to the arm has been shown to accelerate hematoma resolution in both animal and clinical studies. The RICH-2 trial investigated whether RIC could improve the functional outcomes of patients with ICH. Methods: In this investigator-initiated, multicentre, prospective, randomized, sham-controlled, outcome-blinded parallel-group trial conducted in 20 centers in China, patients (age 18 to 80 years) with supratentorial ICH presenting within 24-48 h of ictus who do not need surgical therapy were randomly allocated (1:1, stratified by baseline NIHSS and clot size) to receive RIC or sham RIC for 7 consecutive days after randomization in addition to best medical management. The primary outcome was a score of 0-2 on the modified Rankin Scale at 90 days, analyzed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04657133. Results: Between Apr 22, 2021, and Oct 30, 2023, 458 patients were randomly assigned, with 229 in each group. 134 (29.3%) were women, and 324 (70.7%) were men, the median age was 58 years (IQR 51-68), the median NIHSS score was 9.0 (IQR 7.0-13.0), and the median hematoma volume was 12.6 mL (IQR 10.0-18.0). 156 (68.1%) of 229 patients in the RIC group and 163 (71.2%) of 229 patients in the sham group had a mRS score of 0-2 at 90 days (adjusted RR 0.98; 95% CI 0.88-1.09; adjusted p=0.69). Prespecified subgroup analysis showed a trend in favor of RIC in patients with clot size larger than 20 ml (RR 1.26, 95% CI 0.80-1.98, p=0.31). At 180-day follow-up, 169 (73.8%) of 229 patients receiving RIC and 175 (76.4%) of 229 patients receiving sham RIC achieved a mRS score of 0-2 (adjusted RR 0.98; 95% CI 0.89-1.08; adjusted p=0.64). Serious adverse events occurred in 16 (7.0%) of 229 patients receiving RIC and 12 (5.2%) of 229 patients receiving sham RIC (adjusted RR 1.29, 95% CI, 0.63-2.67, p=0.48). No important unexpected adverse events or side effects of RIC were observed. Conclusions: RIC did not improve the proportion of patients who achieved functional independence 90 days after ICH in patients who did not need surgical therapy. Further studies of RIC in this population should target patients with large clot sizes and address the RIC protocol.