Remote Ischemic Conditioning After Stroke Trial 2: A Phase IIb Randomized Controlled Trial in Hyperacute Stroke.

Abstract
Background Repeated episodes of limb ischemia and reperfusion (remote ischemic
conditioning [RIC]) may protect the brain from ischemic reperfusion injury.
Methods and Results We performed a phase IIb blinded dose-escalation
sham-controlled trial in patients with hyperacute stroke, randomized 1:1 to
receive RIC (four 5-minute cycles) or sham to the nonparetic upper limb, in 3
blocks of increasing dose, starting within 6 hours of ictus. The primary outcome
was trial feasibility (recruitment, attrition). Secondary outcomes included
adherence, tolerability, safety (serious adverse events), plasma biomarkers at
days 1 and 4 (S100-ß protein, matrix metalloproteinase-9, and neuron-specific
enolase), and functional outcome. Sixty participants were recruited from 2
centers (3 per month) with no loss to follow-up: time to randomization 4 hours
5 minutes (SD 72 minutes), age 72 years (12), men 60%, blood pressure
154/80 mm Hg (25/12), National Institutes of Health Stroke Scale 8.4 (6.9), and
55% thrombolyzed. RIC was well tolerated with adherence not differing between RIC
and sham, falling in both groups on day 3 (P=0.001, repeated measures ANOVA)
because of discharge or transfer. S100ß increased in the sham group (mean rise
111 pg/mL [302], P=0.041, repeated measures ANCOVA) but not the RIC group. There were no differences in matrix metalloproteinase-9, neuron-specific enolase,
number with serious adverse events (RIC 10 versus sham 10, P=0.81), deaths (2
versus 4, P=0.36), or modified Rankin Scale score (2 [interquartile range 1-4], 2
[interquartile range, 1-3]; P=0.85). Conclusions RIC in hyperacute stroke is
feasible when given twice daily for 2 days and appears safe in a small population
with hyperacute stroke. A larger phase III trial is warranted. Clinical Trial
Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02779712.
Collections
Date
2019-12Author
England, Tim