The effect of Remote Ischemic Condition on Hematoma growth in patients with Intracerebral Hemorrhage: a subgroup analysis from the RESIST trial.

BACKGROUND: It remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective supplement to standard-of-care management of intracerebral hemorrhage (ICH). METHODS: This is a predefined sub-study to a randomized clinical trial conducted at four stroke centers in Denmark. RIC was induced by using an inflatable cuff on the upper extremity with a cuff pressure of at least 200 mm Hg and sham cuff pressure of 20 mm Hg. Each treatment application consisted of 5 cycles with 5 minutes of inflation followed by 5 minutes of deflation. Hematoma and edema volumes were manually segmented by blinded assessors. The primary end point was the risk of hematoma expansion (growth exceeding 6 mL or a relative growth of more than 33%). RESULTS: Among 1500 prehospital randomized patients, 165 patients had an ICH. Of them, 87 patients were randomly assigned to RIC and 78 to sham treatment. The median age was 71 (IQR: 60, 77), 73 (44%) were females, and the median onset to randomization was 40 minutes (IQR: 30, 69). The median National Institute of Health Stroke Scale score was 12, and 19 patients (12%) had either hematoma evacuation or an external ventricular drain. The study did not provide evidence for a difference in the adjusted risk of 24-hour hematoma expansion in patients treated with RIC compared to sham with a risk difference of -0.052 (95% CI: -0.20;0.10, p=0.504) nor for a difference in the adjusted 7-day hematoma reabsorption rate with a mean difference of 5.47 mL (95% CI: -4.57;15.52, p=0.280). There was no significant difference in edema size at baseline, 24 hours or 7 days. CONCLUSIONS AND RELEVANCE: RIC initiated in the prehospital setting and continued in the hospital did not reduce hematoma expansion or peri-hematoma edema in patients with ICH. TRIAL REGISTRATION: linicalTrials.gov:NCT03481777.