EXTEND-IA TNK demonstrates superiority of tenecteplase over alteplase for prethrombectomy reperfusion
The use of tenecteplase may be a suitable alternative to alteplase prior to endovascular thrombectomy in patients with a large vessel ischaemic stroke, according to results of the EXTEND-IA TNK* study.
In this multicentre (14 centres in Australia and New Zealand), prospective, open-label, blinded-endpoint study, 202 adults within 4.5 hours of onset of a large vessel occlusion ischaemic stroke (median NIHSS** score 17) and with prestroke modified Rankin scale (mRS) ≤3 were randomized 1:1 to receive intravenous tenecteplase (0.25 mg/kg, maximum 25 mg; mean age 70.4 years, 58 percent male) or alteplase (0.9 mg/kg, maximum 90 mg; mean age 71.9 years, 52 percent male) before undergoing endovascular thrombectomy.
The most frequent site of occlusion was the first segment of the middle cerebral artery, affecting 59 and 60 percent of patients on tenecteplase and alteplase, respectively, followed by occlusion of the internal carotid artery (24 percent of each group).
Patients with severe premorbid disability (mRS ≥4) and those unable to undergo imaging with contrast agents were excluded.
The primary endpoint, substantial prethrombectomy reperfusion on the initial catheter angiogram (modified Treatment In Cerebral Infarction 2b/3), occurred more frequently in the group receiving tenecteplase compared with alteplase (22 percent vs 10 percent, odds ratio [OR], 0.26; p=0.002 and 0.02 for noninferiority and superiority, respectively). [ISC 2018, abstract LB2]
The achievement of early neurological recovery (reduction of ≥8 NIHSS points or achieving 0–1 by day 3) was comparable between patients on tenecteplase and alteplase (72 percent vs 69 percent; p=0.66), while ordinal analysis showed a benefit in mRS at 90 days with tenecteplase (OR, 1.7; p=0.037).
Safety outcomes were also similar between patients on tenecteplase and alteplase specifically death (10 percent vs 18 percent, OR, 0.44; p=0.08), incidence of symptomatic intracerebral haemorrhage (1 percent in each group, OR, 1.0; p=0.99), and incidence of parenchymal haematoma (6 percent vs 5 percent, OR, 1.2; p=0.76).
“The idea of the trial is that there are still guidelines recommending bridging thrombolysis … before thrombectomy for patients with a large vessel occlusion. There’s still an opportunity between when you can give thrombolysis and when you can get the artery open within the vascular procedure to intervene with more effective thrombolysis to increase the rate of pre-endovascular perfusion,” explained study co-primary investigator Dr Bruce Campbell from the Royal Melbourne Hospital, Victoria, Australia, who presented the results at the International Stroke Conference 2018 (ISC 2018) in Los Angeles, California, US.
“We think tenecteplase has a lot of promise … it does seem to be more effective at getting the artery open,” he said, highlighting other benefits of tenecteplase including the convenient delivery (single bolus) and potentially cheaper alternative to alteplase in certain healthcare systems.
He acknowledged that the findings may not extend to all patients with strokes as the study cohort consisted of patients with large vessel occlusion ischaemic strokes who were eligible for thrombolysis.
Studies are ongoing to assess the efficacy and safety of the 0.25 mg/kg dose of tenecteplase in nonendovascular patients, while the second part of the EXTEND-IA TNK study is investigating the effects of a 0.25 vs 0.40 mg/kg dose of tenecteplase prior to undergoing endovascular thrombectomy, he said.