Tenecteplase Noninferior to Alteplase for Patients Ineligible for EVT

Tenecteplase is noninferior to alteplase for patients with ischemic stroke who are eligible for standard intravenous thrombolysis but not for endovascular thrombectomy, according to study results published in The Lancet.

Researchers conducted a multicenter, prospective, open-label, randomized controlled, noninferiority trial at 53 centers in China between 2021 and 2022. Patients (N=1417) who experienced an ischemic stroke and had a modified Rankin Scale (mRS) score of 1 or less and were ineligible or refused endovascular thrombectomy were randomly assigned in a 1:1 ratio to receive intravenous tenecteplase 0.25 mg/kg as a single bolus (n=710) or alteplase 0.9 mg/kg with 10% as bolus with the remainder administered over 1 hour (n=707).

The primary efficacy outcome was a mRS score of 0 to 1 at 90 days. The primary safety outcome was the rate of symptomatic intracranial hemorrhage at 36 hours, which was defined using the European Cooperative Acute Stroke Study III (ECASS) criteria.

Participants in the tenecteplase and alteplase cohorts were aged median 67 (IQR, 58-73) and 65 (IQR, 58-72) years, of whom 69% and 68% were men, respectively. Overall, the participants weighed 65 (IQR, 59-75) and 67 (IQR, 60-75) kg, and had National Institutes of Health Stroke Scale (NIHSS) scores of 7 (IQR, 5-10) and 7 (IQR, 6-10) points, respectively.

Onset-to-needle (median range, 178.5-180 min) and door-to-needle (median range, 58-61 min) times were similar between the groups.

At 3 months in the intention-to-treat population, 62% of tenecteplase and 58% of alteplase recipients met the primary efficacy outcome, indicating similar odds of achieving a mRS score of 0 to 1 at 3 months (odds ratio [OR], 1.19; 95% CI, 0.96-1.47). Results were consistent in the per-protocol analysis.

The tenecteplase and alteplase recipients achieved the secondary efficacy outcomes of q mRS scores between 0 and 2 at 3 months (73% vs 72%; P =.74), mRS score at 3 months (median, 1 vs 1 point; P =.38), improvement in NIHSS scores of at least 4 points, or 1 point or less at 24-hours (50% vs 49%; P =.58) or at 7 days or discharge (68% vs 66%; P =.73). Participants in both groups had a Barthel Index of at least 95 (70% vs 69%, respectively; P =.49) and similar European quality of life on visual analogue scale scores (median, 77.7 vs 76.4 points, respectively; P =.23).

No significant interactions were observed in subgroup analyses.

The rate of symptomatic intracranial hemorrhage within 36 hours was 2% in both groups (P =.72). No significant group differences were observed for other safety outcomes. However, tenecteplase recipients tended to be associated with a higher rate of parenchymal hematoma 2 intracranial hemorrhage within 36 hours compared with alteplase recipients (1% vs <1%; P =.053).

Limitations of the study include blinding of outcome evaluations to treatment allocation.

The study authors conclude, “Tenecteplase was non-inferior (and not superior) to alteplase for acute ischemic stroke within 4.5 hours of symptom onset. The trial results support the implementation of intravenous tenecteplase 0.25 mg/kg as an alternative thrombolytic agent to the standard-of-care alteplase in patients with disabling ischemic stroke within 4.5 hours of stroke onset.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.