Intravenous Tenecteplase Compared With Alteplase for Acute Ischemic Stroke in Canada (AcT): Bridging the Gap From...

In the AcT (Alteplase compared to Tenecteplase) trial, tenecteplase (0.25 mg/kg) was non-inferior to alteplase (0.9 mg/kg) for efficacy, and similar in terms of safety in patients with acute ischemic stroke presenting within 4.5 hours of stroke symptom onset. Additional analyses were required to support regulatory approval.

Individual patient data from the AcT study were independently re-analyzed to confirm the robustness of the primary results; adhere to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use reporting guidelines; and fulfill regulatory requirements, such as re-analysis to account for known effect modifiers of thrombolytic therapy and investigation of potential bias at randomization. These data were part of the submission to the European Medicines Agency.

The primary endpoint results from AcT were found to be reproducible, robust, not a chance finding, and without bias, confirming that tenecteplase was non-inferior to alteplase and significantly superior to control. The pharmacologic effect of tenecteplase in relation to sex, age, National Institutes of Health Stroke Scale score (disease severity) at baseline, and onset to treatment time was very similar to the pharmacologic effect of alteplase. Similar event rates for symptomatic intracerebral hemorrhage and death were observed for both groups. In January 2024, tenecteplase was approved for the treatment of acute ischemic stroke in Europe.

Regulatory agencies require specific analyses in order to assess potential bias. Successful customization and extended re-analysis of data from AcT to meet regulatory requirements and adhere to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use reporting guidelines demonstrate that it is possible to bridge the gap between academia and regulatory approval.