Intravenous thrombolytics used between 4.5 to 9 hours after ischemic stroke onset or after waking with symptoms resulted in 0 to minimal neurologic deficits, according to a recent study published in The New England Journal of Medicine.
Researchers conducted a multicenter, randomized, placebo-controlled trial involving adults with ischemic stroke who had hypoperfused but salvageable regions of brain tissue and a clinical severity score of 4 to 26 on the National Institutes of Health Stroke Scale (NIHSS). The primary outcome was defined as a score of 0 or 1 on the modified Rankin scale at 90 days. The risk ratio was adjusted for age and clinical severity at baseline. The secondary outcome was a range of 0 to 2 on the modified Rankin scale at 90 days. The tertiary outcomes were recanalization of the affected artery 24 hours after stroke and major neurologic improvement (indicated by a reduction in the NIHSS score of ≥8 points or a score of 0 or 1 within 24 hours, 72 hours, and 90 days after treatment).
A total of 113 adults were randomly assigned to the alteplase group and 112 to placebo. The trial was terminated after 225 of the planned 310 adults were enrolled due to lack of equipoise after a similar previous trial published positive results. They received alteplase (0.9 mg/kilogram of body weight [maximum 90 mg], administered intravenously as 10% bolus and 90% infusion over 1 hour) or placebo. Safety outcomes included death within 90 days of treatment and symptomatic intracranial hemorrhage.
Primary outcome occurred in 40 individuals (35.4%) from the alteplase group and in 33 (29.5%) in the placebo (adjusted risk ratio [ARR] 1.44; 95% CI, 1.01-2.06; P =.04). Symptomatic intracerebral hemorrhage occurred in 7 individuals (6.2%) from the alteplase group and in 1 (0.9%) from the placebo group (ARR 7.22; 95% CI, 0.97-53.5; P =.05).
Statistical analysis for secondary outcomes showed no significant intergroup difference. Recanalization of the affected artery 24 hours after a stroke occurred in 72 individuals (67.3%) from the alteplase group and in 43 individuals (39.4%) from the placebo group (ARR 1.68; 95% CI, 1.29-2.19). Early major neurologic improvement at 24 hours occurred in 27 individuals (23.9%) from the alteplase group and in 11 individuals (9.8%) from the placebo group (ARR 2.76; 95% CI, 1.45-5.26).
The percentage of individuals who died within 90 days did not differ significantly between the alteplase group and placebo group (13 of 113 [11.5%] vs 10 of 112 [8.9%]; ARR 1.17; 95% CI, 0.57-2.4; P =.67). Death within 7 days occurred in 9 out of 225 individuals (4%) in the trial population — 5 in the alteplase group (2 of whom had symptomatic hemorrhage) and 4 in the placebo group. One individual from the alteplase group had a hemorrhagic transformation of the infarction before the infusion at the site of subsequent bleeding.
Limitations of this study included termination when 73% of the planned sample size was reached and the inability to show a statistically significant difference in the secondary outcome.
Study investigators concluded that among those with ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time of waking with symptoms resulted in a higher percentage of patients with no or minor neurologic deficits when compared to placebo. The limited power of these conclusions, however, warrants further trials of thrombolysis in this time window.
Ma H, Campbell BCV, Parsons MW, et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med. 2019;380(19):1795-1803.