Khatri P, et al. - In patients with National Institutes of Health Stroke Scale (NIHSS) scores of 0 to 5 whose deficits are not clearly disabling, the efficacy and safety of alteplase were evaluated. Findings suggested that treatment with alteplase vs aspirin did not increase the odds of favorable functional outcome at 90 days in patients with minor nondisabling acute ischemic stroke. However, the very early study termination precludes any definitive conclusions.

Methods

• The PRISMS trial was designed as a 948-patient, phase 3b, double-blind, double-placebo, multicenter randomized clinical trial comparing alteplase with aspirin for emergent stroke at 75 stroke hospital networks in the US.
• Subjects with acute ischemic stroke whose deficits were scored as 0 to 5 on the NIHSS and judged not clearly disabling and in whom study treatment could be started within 3 hours of onset were qualified and enlisted from May 30, 2014 to December 20, 2016, with final follow-up on March 22, 2017.
• After that, patients were randomly allocated to receive intravenous alteplase at the standard dose (0.9 mg/kg) with oral placebo (n=156) or oral aspirin, 325 mg, with intravenous placebo (n=157).
• The primary outcome was the difference in favorable functional outcome, characterized as a modified Rankin Scale score of 0 or 1 at 90 days through Cochran-Mantel-Haenszel test stratified by pretreatment NIHSS score, age, and time from onset to treatment.
• Due to early termination of the trial, before unblinding or interim analyses, the revised plan was to investigate the risk difference of the primary outcome by a linear model adjusted for the same factors.
• Symptomatic intracranial hemorrhage (sICH) within 36 hours of intravenous study treatment was the primary safety end point.

Results

• The study results showed that among 313 patients enlisted at 53 stroke networks (mean age, 62 [SD, 13] years; 144 [46%] women; median NIHSS score, 2 [interquartile range {IQR}, 1-3]; median time to treatment, 2.7 hours [IQR, 2.1-2.9]), 281 (89.8%) finished the trial.
• It was observed that 122 patients (78.2%) in the alteplase group vs 128 (81.5%) in the aspirin group achieved a favorable outcome (adjusted risk difference, -1.1%; 95% CI, -9.4% to 7.3%) at 90 days.
• Findings revealed that 5 alteplase-treated patients (3.2%) vs 0 aspirin-treated patients had sICH (risk difference, 3.3%; 95% CI, 0.8%-7.4%).