International Stroke Conference
February 6–8, 2019

Session: “Extending the Thrombolytic Time Window to 9 Hours for Acute Ischemic Stroke using Perfusion Imaging Selection – The Final Result”

Kara Jo Swafford, MD

Henry Ma, PhD, from Monash University in Melbourne, Australia, presented the final results of the EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) trial at the 2019 International Stroke Conference in Honolulu, HI, on Friday, February 8. The EXTEND trial was a randomized, multicenter, double-blinded, placebo-controlled phase III trial of intravenous alteplase versus placebo designed to test the hypothesis that the time window for treatment could be as long as 9 hours from stroke onset (including wake-up stroke patients with unknown last known well). Recruitment for the EXTEND trial halted in June 2018 after the WAKE-UP trial demonstrated benefit from imaging-guided intravenous thrombolysis in acute stroke patients with unknown last known well. The WAKE-UP trial used MRI rather than CT perfusion for patient selection.

Despite early termination, the EXTEND trial enrolled 225 patients at centers in Australia, Taiwan, New Zealand and Finland. Participants were stratified into three groups based on stroke onset time: 4.5 to 6 hours, more than 6 to 9 hours and wake-up stroke. CT perfusion or MRI perfusion/diffusion and RAPID software for automated processing were utilized, and those with significant penumbral mismatch were selected. Primary endpoint was excellent functional outcome at 90 days, defined as modified Rankin Scale (mRS) score of 0 to 1.

Median time from last known well to treatment was 10 hours in the alteplase arm and 9 hours for placebo. Approximately 70% of alteplase-treated and 72% of placebo participants had a large vessel occlusion, although none had mechanical thrombectomy. Thrombolysis up to 9 hours improved functional outcome at 90 days compared to placebo (37% versus 29%; adjusted RR 1.45; 95% CI, 1.01-2.10; P = .045). Symptomatic intracranial hemorrhage was higher in the treatment arm compared to placebo, but Dr. Ma explained that this has been observed in other thrombolysis trials, was not associated with higher mortality and did not significantly affect functional outcome at 90 days. Results of the EXTEND trial suggest the selection of patients for thrombolytic therapy should be based on salvageable penumbral tissue using readily available CT perfusion or MRI diffusion/perfusion imaging rather than solely on the basis of time.