Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke: The RICAMIS Randomized Clinical Trial

Abstract

Importance: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking.

Objective: To assess the efficacy of RIC for acute moderate ischemic stroke.

Design, setting, and participants: This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021.

Interventions: Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971).

Main outcomes and measures: The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set.

Results: Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group.

Conclusions and relevance: Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention.

Trial registration: ClinicalTrials.gov Identifier: NCT03740971.

Figure 1.. Recruitment, Randomization, and Patient Flow in the RICAMIS Randomized Clinical Trial

Baseline characteristics and procedural details in patients missing primary outcome are shown in eTable 5 in Supplement 3. mRS indicates modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; and RICAMIS, Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke. ^aTime from randomization to last contact of patients missing primary outcome in the remote ischemic conditioning group was a median of 5 days (IQR, 0-10). ^bTime from randomization to last contact of patients missing primary outcome in the control group was a median of 7 days (IQR, 0-12).

Figure 2.. Distribution of Modified Rankin Scale Scores at 90 Days in the Full Analysis Set

The raw distribution of scores is shown. Scores range from 0 to 6 (0 = no symptoms, 1 = symptoms without clinically significant disability, 2 = slight disability, 3 = moderate disability, 4 = moderately severe disability, 5 = severe disability, and 6 = death). The odds ratio was 1.29 (95% CI, 1.09-1.52), and the P value was .003; the adjusted odds ratio was 1.37 (95% CI, 1.16-1.63), and the adjusted P value was <.001.