A neuroprotectant finally beat placebo in acute ischaemic stroke

Design

Multicentre, double-blind, placebo-controlled phase 3 randomised trial

Population

997 adults aged 18–80 with acute ischaemic stroke, baseline NIHSS 7–20, no prestroke disability, within 48 hours of onset, at 32 Chinese hospitals

Primary outcome

Modified Rankin Scale score of 0–1 at 90 days

Effect

69.7% vs 56.3%; relative risk 1.24 (95% CI 1.12–1.36); risk difference 13.3 percentage points (7.2–19.3)

LAIS randomised 998 adults at 32 Chinese hospitals who presented within 48 hours of an ischaemic stroke, with a baseline National Institutes of Health Stroke Scale (NIHSS) score of 7 to 20 and no prior disability, to intravenous loberamisal 40 mg daily for ten days or placebo, on top of standard care. Loberamisal targets the postsynaptic density 95 pathway and the α2-GABA-A receptor.

At 90 days, 69.7% of the loberamisal group had a modified Rankin Scale score of 0 or 1 — functional independence with no significant disability — against 56.3% on placebo (relative risk 1.24, 95% CI 1.12–1.36; risk difference 13.3 percentage points, 95% CI 7.2–19.3). Adverse events were near-identical between arms (87.8% vs 88.7%), serious adverse events were fewer on the drug (8.6% vs 10.7%), and deaths were 1.2% versus 2.0%.

For a clinician outside neurology, the context is what makes this notable rather than the numbers. Neuroprotection in stroke has a near-unbroken record of promising phase 2 results that vanish in phase 3, and this trial was conducted entirely in one country, in a population with a median NIHSS of 8 — moderate strokes — and an unusually wide 48-hour window. The effect size is larger than most reperfusion therapies achieve. That is a reason for interest and for caution in equal measure.

• Nothing changes in your stroke pathway today — thrombolysis and thrombectomy within their windows remain the interventions that matter.
• Expect this to be raised by patients and families; the honest answer is that the drug is not licensed or available outside trials in most countries.
• Note the entry criteria if a replication trial opens locally: NIHSS 7–20, no prior disability, within 48 hours.
• Keep doing the things with established benefit — early swallow assessment, mobilisation, blood pressure and glucose control, and secondary prevention started before discharge.

Why it matters

Every neuroprotectant before this one failed at phase 3, so either the field has turned a corner or this result will not replicate.

Don't overread it

One trial, in one country, in moderate strokes — this is not yet a treatment, and it is not licensed anywhere as one.

The statistics, in plain English

A risk difference of 13.3 percentage points means about one extra patient in eight walks away without significant disability — a number needed to treat of roughly 8, which would be remarkable if it holds. The confidence interval (7.2 to 19.3) is entirely on the benefit side, so the result is not a chance finding within this trial. What a confidence interval cannot tell you is whether a single-country trial generalises, and that is the open question here.

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