April 7, 2020
EXTEND-IA TNK Part 2 Trial Findings Published
April 7, 2020—The EXTEND-IA TNK Part 2 trial investigated the effect of intravenous tenecteplase dose on cerebral reperfusion before thrombectomy in patients with large vessel occlusion ischemic stroke. Specifically, the trial sought to determine whether a 0.40-mg/kg dose of tenecteplase, compared with 0.25 mg/kg of tenecteplase, improved cerebral reperfusion before endovascular thrombectomy in these patients. The background of the study is that, compared with alteplase, intravenous thrombolysis with tenecteplase is known to improve reperfusion before endovascular thrombectomy for ischemic stroke.
This randomized clinical trial showed that the percentage of patients who achieved substantial reperfusion before endovascular thrombectomy was 19.3% in each tenecteplase dose group, with no statistically significant difference. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned, concluded the investigators in JAMA.
From December 2017 to July 2019, the randomized clinical trial included 300 adult patients (mean age, 72.7 years; 141 [47%] women) at 27 hospitals in Australia and one hospital in New Zealand using open-label treatment and blinded assessment of radiologic and clinical outcomes. Follow-up continued until October 2019. All 300 patients who were randomized completed the trial.
The patients had experienced ischemic stroke caused by occlusion of the intracranial internal carotid, basilar, or middle cerebral artery and were treated < 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria. Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) was given as a bolus before endovascular thrombectomy.
The study's primary outcome was reperfusion of > 50% of the involved ischemic territory before thrombectomy, assessed by consensus of two blinded neuroradiologists.
In JAMA, the investigators reported that the number of patients with > 50% reperfusion of the previously occluded vascular territory was 29 (19.3%) of 150 in both groups (unadjusted risk difference, 0%; 95% confidence interval [CI], -8.9%– -8.9%; adjusted risk ratio, 1.03; 95% CI, 0.66–1.61; P = .89).
Prespecified secondary outcomes were:
- Level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0–6)
- mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days
- mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days
- Substantial neurologic improvement at 3 days
- Symptomatic intracranial hemorrhage within 36 hours
- All-cause death
Among the six secondary outcomes, there were no significant differences in any of the four functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7%; 95% CI, -5.6%–1%) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3%; 95% CI, -0.5%–7.2%), reported the investigators in JAMA.