Exemplar Trial Overview - AcT. (28-min video & 58-slide presentation)

• Summary: Intravenous alteplase improves clinical outcomes in patients with acute ischaemic stroke and is the global standard of care. Tenecteplase, a genetically modified variant of alteplase, is preferred over alteplase in patients with acute myocardial infarction because of its ease of use as a single bolus and a more favourable benefit-to-risk profile. Dr. Bijoy Menon overviews the AcT pragmatic trial which answers the question: “In patients with acute ischemic stroke eligible for intravenous thrombolysis, is tenecteplase non-inferior to alteplase for 90-day functional independence assessed using the modified Rankin Scale?”

Menon BK, et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. Lancet. 2022 Jul 16;400(10347):161-169. (9-page paper) * An institutional login (e.g., university or research institute e-mail address) is required to access this material.

• Summary: Publication in The Lancet describing a multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT) with the aim of determining whether tenecteplase given as a single bolus might increase reperfusion compared with the standard of care (i.e., intravenous thrombolysis with alteplase bolus followed by infusion). Patients were enrolled from 22 primary and comprehensive stroke centres across Canada and were randomly assigned (1:1) to either intravenous tenecteplase or alteplase. The primary outcome was the proportion of patients who had a modified Rankin Scale score of 0-1 at 90-120 days after treatment, assessed through blinded review in all patients who were randomly assigned to treatment who did not withdraw consent.

Faris H, et al. Ethical Justification for Deferral of Consent in the AcT Trial for Acute Ischemic Stroke. Stroke. 2022 Jul;53(7):2420-2423. (4-page paper)

• Summary: Obtaining informed consent has been recognized as a challenge to the completion of modern acute stroke trials. Therefore, an increasing number of major trials have sought to enrol patients through alterations of consent, i.e., through deferral of consent. This paper provides a more explicit and rigorous approach to the justification of deferral of consent in the AcT trial.

Sajobi T, et al. AcT Trial: Protocol for a Pragmatic Registry-Linked Randomized Clinical Trial. Stroke Vasc Intervent Neurol. 2022, 2(5). (9-page paper)

• Summary: This protocol describes a pragmatic, registry-linked, randomized (1:1) controlled, open-label parallel group clinical trial (AcT: Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke). The trial examines if intravenous tenecteplase is noninferior to intravenous alteplase in patients with acute ischemic stroke eligible for intravenous thrombolysis in clinical routine care.

Shamy MC, et al. Consent-Related Outcomes in the Alteplase Compared to Tenecteplase Trial. Neurology. 2024 Nov 26;103(10):e209974. (5-page paper)

• Summary: In recent years, researchers have aimed to address the challenges of obtaining informed consent for participation in acute stroke trials. This study describes outcomes related to the use of deferral of consent in the AcT pragmatic trial, where participants at three sites were invited to complete a survey of attitudes regarding consent procedures in AcT, and their attitudes towards consent for acute stroke trials in general.

Ferguson E, Lang E. In acute ischemic stroke, early IV tenecteplase was noninferior to alteplase for excellent functional outcome. Ann Intern Med. 2022 Nov;175(11):JC124. (1-page summary) * An institutional login (e.g., university or research institute e-mail address) is required to access this material.

• Summary: A one-page summary of the AcT trial, overviewing the research question, design, blinding, setting, patient population, intervention, results, and funding. A brief commentary on the trial is also provided.

Menon BK, et al. Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke (AcT). ClinicalTrials.gov identifier: NCT03889249. Updated 2023-05-12. (8-section website)

• Summary: Public registration of the trial (i.e., study overview, contacts and locations, study plan, collaborators and investigators, publications, study record dates).