In this official Canadian Stroke Consortium (CSC) episode, we dive deep into the landmark ACT Trial (Alteplase Compared to Tenecteplase). Dr. Bijoy Menon, the trial's Principal Investigator, joins the show alongside Co-Principal Investigator Dr. Rick Swartz to discuss the design, execution, and practice-changing results of this pragmatic Phase 3 trial.The ACT trial was a pragmatic, multicenter, open-label, registry-linked, randomized controlled non-inferiority trial.Scope: Conducted across 22 stroke centers in Canada.Timeline & Volume: Between December 2019 and January 2022, the trial enrolled 1,600 patients aged 18 or older with disabling acute ischemic stroke presenting within 4.5 hours of symptom onset.Randomization: Patients were randomized 1:1 to receive either:Tenecteplase: 0.25 mg/kg (maximum 25 mg) as a single bolus.Alteplase: 0.9 mg/kg (maximum 90 mg) as a bolus followed by a 60-minute infusion.The study met its prespecified non-inferiority threshold, demonstrating that Tenecteplase is a reasonable alternative to Alteplase.Primary Outcome (Functional Independence): An mRS score of 0-1 at 90-120 days occurred in 36.9% of Tenecteplase patients versus 34.8% of Alteplase patients. This represents an unadjusted risk difference of 2.1%.Safety Profile: Safety outcomes were similar between the two groups:Symptomatic Intracerebral Hemorrhage: 3.4% (TNK) vs 3.2% (tPA).90-day Mortality: 15.3% (TNK) vs 15.4% (tPA).A prespecified secondary analysis examined 520 patients (33% of the trial population) with LVOs (including ICA, M1/M2-MCA, and basilar artery).Functional Outcomes: Among LVO patients, 32.7% in the Tenecteplase group achieved mRS 0-1 compared to 29.6% in the Alteplase group.Reperfusion Rates: For the 405 LVO patients who underwent thrombectomy, successful reperfusion was comparable on initial angiography (9.2% TNK vs 10.5% tPA) and final angiography (84.5% vs 88.9%).Conclusion: Treatment outcomes were not modified by the baseline occlusion site, and rates of functional independence, hemorrhage, and mortality remained similar between groups.A separate analysis highlighted that "time is brain" applies equally to both agents.Onset-to-Needle: Each 30-minute reduction in onset-to-needle time was associated with a 1.8% increase in the probability of achieving a good outcome (mRS 0-1).Door-to-Needle: Every 10-minute reduction in door-to-needle time was associated with a 0.2% increase in probability of a good outcome.Effect: The effect of time to treatment on clinical outcomes was similar regardless of which thrombolytic agent was used.The investigators emphasized the practical advantages of Tenecteplase over Alteplase:Ease of Administration: The single-bolus administration of Tenecteplase (5-10 seconds) eliminates the need for a 60-minute infusion pump.Transport Efficiency: The single bolus facilitates rapid treatment and easier patient transfer for endovascular therapy when needed.Robust Evidence: The ACT trial's large sample size and pragmatic design provide the necessary evidence to support Tenecteplase as a standard of care for all patients meeting standard thrombolysis criteria.Dr. Bijoy Menon: Principal Investigator of the ACT Trial; Stroke Neurologist and Professor at the University of Calgary.Dr. Rick Swartz: Co-Principal Investigator; Stroke Neurologist at Sunnybrook Health Sciences Centre, University of Toronto.Reference:Menon BK, et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke (ACT): a pragmatic, registry-linked, randomised, open-label, phase 3, non-inferiority trial. The Lancet. 2022.

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