Therapeutic hypothermia for acute ischaemic stroke. Results of a European multicentre, randomised, phase III clinical trial

Abstract

<div><h2>Introduction</h2></div><p>We assessed whether modest systemic cooling started within 6 hours of symptom onset improves functional outcome at three months in awake patients with acute ischaemic stroke.</p><div><a></a><div><h2>Patients and methods</h2></div><p>In this European randomised open-label clinical trial with blinded outcome assessment, adult patients with acute ischaemic stroke were randomised to cooling to a target body temperature of 34.0–35.0°C, started within 6 h after stroke onset and maintained for 12 or 24 h , versus standard treatment. The primary outcome was the score on the modified Rankin Scale at 91 days, as analysed with ordinal logistic regression.</p></div><div><a></a><div><h2>Results</h2></div><p>The trial was stopped after inclusion of 98 of the originally intended 1500 patients because of slow recruitment and cessation of funding. Forty-nine patients were randomised to hypothermia versus 49 to standard treatment. Four patients were lost to follow-up. Of patients randomised to hypothermia, 15 (31%) achieved the predefined cooling targets. The primary outcome did not differ between the groups (odds ratio for good outcome, 1.01; 95% confidence interval, 0.48–2.13; <i>p</i> = 0.97). The number of patients with one or more serious adverse events did not differ between groups (relative risk, 1.22; 95% confidence interval, 0.65–1.94; <i>p</i> = 0.52).</p></div><div><a></a><div><h2>Discussion</h2></div><p>In this trial, cooling to a target of 34.0–35.0°C and maintaining this for 12 or 24 h was not feasible in the majority of patients. The final sample was underpowered to detect clinically relevant differences in outcomes.</p></div><div><a></a><div><h2>Conclusion</h2></div><p>Before new trials are launched, the feasibility of cooling needs to be improved.<br /></p></div>