HONOLULU -- Thrombolytics work out to a 9-hour window in acute and wake-up ischemic strokes when automated CT or MR scans select candidates with salvageable brain, the EXTEND trial showed.
Functional outcomes were improved, with a 44% greater adjusted likelihood of excellent functional outcome (P=0.04) for patients treated after imaging showed a penumbral mismatch at 4.5 to 9 hours after onset or wake-up stroke compared with others who got placebo.
Thrombolysis increased the proportion with a 90-day modified Rankin Scale (mRS) score of 0-1 to 35% compared with 29%, Henry Ma, MBBS, of Monash University in Melbourne, Australia, reported here at the American Heart Association International Stroke Conference (ISC).
Those primary intent-to-treat analysis results, initially reported at the 2018 World Stroke Congress, were supported by per protocol analysis showing a similar 45% increase in likelihood of mRS 0-1 with lytic treatment adjusted for initial stroke severity and age (37% vs 29%, P=0.045).
While there was six-fold more symptomatic intracranial hemorrhage at 36 hours with tissue plasminogen activator (tPA, 6% vs 1%) -- "consistent with other thrombolytic trials," the difference wasn't significant at P=0.071 and there were no differences in mortality (10.0% vs 9.5%, P=0.94).
Ma told attendees at the late-breaking trial session that the risks didn't outweigh the positive result on functional outcomes.
"EXTEND is the first positive thrombolysis trial in an extended time window using automated penumbral imaging," he said.
These findings build on the WAKE-UP trial, which had shown that MRI imaging could select a group of ischemic stroke patients with unknown time of symptom onset who were within the 4.5-hour window for lytic administration.
"I think it's very important because there are a lot of patients out there that we couldn't treat based on current guidelines -- tPA 4.5 hours. Now we know in select patients, that it's safe and efficacious and improves outcomes. So we're going to be able to treat more patients," ISC session moderator Louise McCullough, MD, PhD, of the University of Texas Health Science Center at Houston, told MedPage Today.
"How this fits with thrombectomy kind of remains to be determined. Do you do the IV tPA or do you go right to thrombectomy in these late-presenting window patients? We'll find out over the next few years," she added.
"I think the major impact will be in the areas where there is no thrombectomy, because thrombectomy takes a lot of the patients now," Ma told MedPage Today. "Now you can have more patients who drip and ship with tPA on board."
About 70% of patients had a large vessel occlusion in the trial, although none got thrombectomy.
Patients were selected based on the same type of imaging often used to assess candidates for thrombectomy -- the RAPID software for automated CT perfusion or MR perfusion penumbral mismatch assessment. Criteria were a hypoperfusion-to-core volume ratio greater than 1.2, a perfusion lesion-core absolute difference over 10 mL, and an ischemic core lesion volume of at least 70 mL.
McCullough noted that use of automated software for both tPA and thrombectomy makes it more practical and potentially cost-saving for centers to adopt and train staff.
"Especially if you don't have really fast access to a thrombectomy-capable center, now at least we can start the IV tPA and the patient will have something on-board," she told MedPage Today. "That's why that study's so important and exciting. Those people that were thought not to be salvaged can now be salvaged."
The trial included 225 of the planned 310 patients before the trial was terminated early upon publication of the WAKE-UP trial. Randomized patients received 0.9 mg/kg tPA or placebo.
Secondary per protocol outcomes for tPA compared with placebo included:
- 35% higher adjusted RR of a good functional outcome (mRS 0-2 at 90 days, P=0.022)
- 2.67-fold greater adjusted likelihood of early neurologic improvement with a reduction of at least 8 points on the NIH Stroke Scale score or to 0-1 at 24 hours (25% vs 10%, P=0.002)
- 78% greater adjusted likelihood of 90% reperfusion at 24 hours (51% vs 28%, P=0.001)
- 71% higher adjusted odds of recanalization at 24 hours (70% vs 40%, P<0.001)
Ma cautioned that the per protocol analysis may have been underpowered due to early termination with fewer than planned patients.
The study was supported by the Australian National Health and Medical Research Council and CSIRO.
Boehringer Ingelheim supplied the study drug. iSchemaView provided the RAPID software platform.
Ma disclosed no relevant relationships with industry.
Beyond Imaging: the paradox of AI and medical imaging innovation
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