Journal Club Summary
Ma H, et al N Engl J Med. 2019 May 9;380(19):1795-1803
Editorial: Image-Guided Intravenous Alteplase for Stroke – Shattering a Time Window.
Question and Methods: This was an international, multicenter, randomized, placebo-controlled trial of intravenous tPA in patients with stroke who presented 4.5-9 hours after symptom onset and who had salvageable penumbra tissue on perfusion imaging.
Findings: More patients in the tPA group had complete functional independence (mRS 0-1) at 90 days versus those who received placebo (35.4 vs 29.5%); however, rates of symptomatic intracranial hemorrhage were also higher in the tPA group (6.2% vs 0.9%).
Limitations: Major limitations include early stopping of the trial (225/310 patients), and that the study population was selected using perfusion software that is not currently available in our centre.
Interpretation: Until perfusion imaging software is readily available in our stroke centre, this trial will not change the current standard time window to consider tPA for patients with acute ischemic stroke.
By: Dr. Ariel Hendin
Interim Analyses and Stopping Rules
In clinical trials, an interim analysis is one that is conducted before data collection has been completed to determine if there are safety issues or if the study should be stopped early. These interim analyses are evaluated by an independent Data Safety Monitoring Board that is at arm’s length from the investigators. The DSMB has the authority to recommend early termination if the study intervention is clearly better than control (for benefit) or if there is so little difference between groups that full enrolment will not show a difference (for futility). Statistical stopping rules should be used to adjust the interim P-values to a much severe level, e.g. <0.001 instead of <0.05 using methods described by Pocock and O’Brien & Fleming, among others.
By: Dr. Ian Stiell