Efficacy and Safety of Minocycline in Patients With Acute Ischaemic Stroke Receiving Intravenous Thrombolysis

Overview

The aim of this study is to assess the efficacy and safety of minocycline in improving functional outcome among patients with acute ischaemic stroke receiving intravenous thrombolysis.

Minocycline, a broad-spectrum tetracycline antibiotic, has been shown to possess a wide range of cytoprotective properties independent of its antibacterial activity, which have translated into promising therapeutic potential for acute ischaemic stroke. Specifically, the drug improves post-stroke outcomes by targeting post-ischaemic neuroinflammation through multiple mechanisms. Early-phase clinical trials first indicated that minocycline treatment, initiated within 6-24 hours after stroke, could improve functional outcomes for up to 90 days. This promise was recently substantiated by the EMPHASIS trial, which demonstrated that minocycline administered within 72 hours of ischaemic stroke onset significantly improved 90-day functional outcomes compared to placebo, with a favorable safety profile. Furthermore, preclinical research has shown that combining minocycline with t-PA can improve thrombolytic efficacy, extend the therapeutic time window, and reduce the risk of hemorrhagic transformation. Hence, this study-a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial-aims to evaluate whether minocycline improves functional outcomes in patients with acute ischaemic stroke undergoing intravenous thrombolysis. Patients aged 18 to 80 years with a newly diagnosed ischaemic stroke (NIHSS score of 6-25 and Ia ≤1), who have received/are planned to receive intravenous thrombolysis within 4.5 hours of onset or within an extended window of 4.5-24 hours based on guideline recommendations, and can be treated with the study drug either before thrombolysis or within 2 hours after its initiation, will be enrolled. Eligible patients will be randomly assigned in a 1:1 ratio to receive minocycline or placebo. The primary efficacy outcome is an excellent functional outcome (a mRS score of 0 or 1) at 90 days. The secondary efficacy outcomes include a good functional outcome (a mRS score of 0 to 2) at 90 days, the ordinal distribution of mRS score at 90 days, quality of life (EQ-5D) score at 90 days, a Barthel Index score of at least 95 at 90 days, the change from baseline in the NIHSS score at 6 days, and major neurologic improvement at 6 days (defined as a decrease from baseline of ≥ 4 points on the NIHSS, or an NIHSS score of ≤1). Safety outcomes include diarrhoea, enteritis, and constipation within 6 days, symptomatic intracranial hemorrhage within 6 days, any bleeding events, adverse events or serious adverse events within 90 days. Randomized participants will be interviewed at screening/baseline period, 6 days, 30±3 days, 60±5 days, and 90±7 days after randomization.

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

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