Multi-Center Randomized Phase II Clinical Trial on Remote Ischemic Conditioning in Acute Ischemic Stroke Within 9 Hours of Onset in Patients Ineligible to Recanalization Therapies (TRICS-9): Study Design and Protocol

Abstract

Aim: To assess the efficacy of remote ischemic conditioning (RIC) in patients with ischemic stroke within 9 h of onset, that are not candidates for recanalization therapies.Sample Size Estimates: A sample size of 80 patients (40 in each arm) should yield 80% power to detect a 20% difference in early neurological improvement at 72 h at p = 0.05, two sided.Methods and Design: TRICS-9 is a phase II, multicenter, controlled, block randomized, open-label, interventional clinical trial. Patients recruited in Italian academic hospitals will be randomized 1:1 to either RIC plus standard medical therapy or standard medical therapy alone. After randomization, RIC will be applied manually by four alternating cycles of inflation/deflation 5 min each, using a blood pressure cuff around the non-paretic arm.Study Outcomes: The primary efficacy outcome is early neurological improvement, defined as the percent change in the National Institute of Health Stroke Scale (NIHSS) at 72 h in each arm. Secondary outcomes include early neurologic improvement at 24 and 48 h, disability at 3 months, rate of symptomatic intracerebral hemorrhage, feasibility (proportion of patients completing RIC), tolerability after RIC and at 72 h, blood levels of HIF-1α, and HSP27 at 24 h and 72 h.Discussion/Conclusion: RIC in combination with recanalization therapies appears to add no clinical benefit to patients, but whether it is beneficial to those that are not candidates for recanalization therapies is still to be demonstrated. TRICS-9 has been developed to elucidate this issue.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT04400981.

Harmonization of sensorimotor deficit assessment in a registered multicentre pre-clinical randomized controlled trial using two models of ischemic stroke

“…Our scoring system would help align experimental stroke models to the clinical setting, where stroke patients are assessed by standard scoring systems, like the NIHSS for injury severity and the mRS for longer term outcome. We used here the neuroscore to assess an early deficit, in line with the primary endpoint of the TRICS preclinical trial 11 and its parallel clinical trial, 32 i.e. observing an early neurological improvement after RIC.…”

Determination of significant parameters in remote ischemic postconditioning for ischemic stroke in experimental models: A systematic review and meta‐analysis study

“…4 The research on RIPostC for ischemic stroke has been conducted in experimental models for over a decade, accumulating a large number of published scientific articles, 3,6,9 and some institutions even conducted the clinical randomized trials. [10][11] However, studies designed different schemes of RIPostC and utilized various outcome measures according to their research objectives. This results in the reliability and credibility of the conclusions drawn from individual original research articles only with a few animals are limited, making it difficult to translate into valid guidance for clinical practice.…”

“…The research on RIPostC for ischemic stroke has been conducted in experimental models for over a decade, accumulating a large number of published scientific articles, 3,6,9 and some institutions even conducted the clinical randomized trials 10–11 . However, studies designed different schemes of RIPostC and utilized various outcome measures according to their research objectives.…”