SAHRANG: Subarachnoid Hemorrhage Recovery and Galantamine - A pilot multicenter randomized placebo-controlled trial

TL;DR

This pilot study tested galantamine's safety in subarachnoid hemorrhage patients and found no significant differences in side effects or mortality compared to a placebo.

Contribution

A novel pilot trial evaluating galantamine's tolerability and safety in treating subarachnoid hemorrhage.

Findings

Galantamine and placebo showed similar safety profiles in SAH patients.

Bradycardia was the most common adverse event, occurring in 37% of participants.

Mortality rates were not significantly different between the galantamine and placebo groups.

Abstract

Background
Subarachnoid hemorrhage (SAH) causes life-long neurologic dysfunctions. Peripheral inflammatory processes as a reaction to brain injury has been shown to worsen outcomes after SAH. Galantamine has been shown to reduce proinflammatory microglial activities and improve synaptic connections. We hypothesize that galantamine treatment after SAH mitigates inflammation-mediated neuronal injury and improve outcomes. We conducted a pilot clinical trial to examine the tolerability and safety of galantamine in SAH patients.
Methods
This prospective, multicenter, double-blind, randomized, placebo-controlled study contiguously screened and enrolled adult patients presenting with aneurysmal subarachnoid hemorrhage of the Fisher grade 3 within 72 hours of symptom onset. A total of 60 patients were enrolled with a 1:1 ratio to two treatment arms. The first 30 patients were randomized to galantamine 8mg every 12 hours or a placebo, and the other 30 patients to either galantamine 12mg every 12 hours or a placebo. All medications were started within 36 hours after securing the aneurysm and continued for 90 days. Primary outcomes—tolerability as assessed by the number of patients who stop study medication due to adverse events associated with the study drug and mortality due to the study drug—were assessed at 90 days.
Results
There were no differences in tolerability and safety between the two groups. Bradycardia was the most common adverse event (37%), followed by clinical seizure (3%) and skin rash (3%). One subject in the galantamine group discontinued medication due to a skin rash, and another subject from the placebo group discontinued due to nausea (p=0.92). Mortality did not differ between the two groups. At 90 days, one subject from the galantamine group and four subjects from the placebo group died (p=0.34).
Conclusions
Galantamine and placebo did not differ in their side effects and safety profiles when administered to SAH patients during the early and subacute stages of the disease.