IRIS, a randomised, double-blind, placebo-controlled trial of interleukin-6 receptor inhibition undergoing endovascular treatment in acute anterior circulation ischaemic stroke: study rationale and design.

Abstract

Rationale: Neuroprotective strategies based on reperfusion therapy hold substantial promise for acute ischaemic stroke (AIS). Preclinical research indicates that tocilizumab, an interleukin-6 receptor antagonist, can attenuate ischaemia-reperfusion damage by exerting anti-inflammatory and neuroprotective effects.

Aim: To determine tocilizumab's efficacy and safety when combined with endovascular thrombectomy (EVT) in patients with acute anterior circulation large vessel occlusion (LVO).

Sample size estimates: To determine a 30% decrease in average infarct core volume comparing the intervention and historical control groups (mean increase of 18.7 mL (SD=9.7 mL) post-thrombectomy) via a two-sided test (alpha=0.05, power=80%), accounting for a 10% drop-out rate, we plan to recruit 108 participants.

Methods and design: This trial is designed as a randomised, multicentre, double-blind, placebo-controlled trial. Patients will be randomly and evenly allocated to the tocilizumab or placebo groups.

Study outcomes: The primary endpoint is the change in infarct core volume between baseline and 72 hours post-treatment. Secondary outcomes include the 90-day modified Rankin scale score (0-2, indicating functional independence). The key safety endpoints include 90-day mortality and symptomatic intracerebral haemorrhage within 72 hours after EVT.

Discussion: Administering tocilizumab within 24 hours of stroke as an adjunct to EVT may effectively reduce the infarct core volume for patients experiencing AIS with anterior circulation LVO, potentially improving functional outcomes in these patients.