The START trial is a prospective, response-adaptive randomized clinical trial designed to enroll 1500 patients to determine the optimal delay time to initiate anticoagulation after ischemic stroke.
RCT (n=1,500)
response adaptive randomization
Yes
Does a specific delay time to initiate anticoagulation after atrial fibrillation-related stroke reduce the composite of hemorrhagic conversion and recurrent ischemic stroke?
The START trial methodology outlines a pragmatic, adaptive randomized approach to determine the optimal timing for initiating direct oral anticoagulants after an AF-related ischemic stroke.
RATIONALE: An estimated 15% of all strokes are associated with untreated atrial fibrillation. Long-term secondary stroke prevention in atrial fibrillation is anticoagulation, increasingly with non-vitamin K oral anticoagulants. The optimal time to initiate anticoagulation following an atrial fibrillation-related stroke that balances hemorrhagic conversion with recurrent stroke is not yet known. AIMS: To determine if there is an optimal delay time to initiate anticoagulation after atrial fibrillation-related stroke that optimizes the composite outcome of hemorrhagic conversion and recurrent ischemic stroke. SAMPLE SIZE ESTIMATES: The study will enroll 1500 total subjects split between a mild to moderate stroke cohort (1000) and a severe stroke cohort (500). METHODS AND DESIGN: This study is a multi-center, prospective, randomized, pragmatic, adaptive trial that randomizes subjects to four arms of time to start of anticoagulation. The four arms for mild to moderate stroke are: Day 3, Day 6, Day 10, and Day 14. The time intervals for severe stroke are: Day 6, Day 10, Day 14, and Day 21. Allocation involves a response adaptive randomization via interim analyses to favor the arms that have a better risk-benefit profile. STUDY OUTCOMES: The primary outcome event is the composite occurrence of an ischemic or hemorrhagic event within 30 days of the index stroke. Secondary outcomes are also collected at 30 and 90 days. DISCUSSION: The optimal timing of direct oral anticoagulants post-ischemic stroke requires prospective randomized testing. A pragmatically designed trial with adaptive allocation and randomization to multiple time intervals such as the START trial is best suited to answer this question in order to directly inform current practice on this question.
King et al. (Sun,) conducted a rct in atrial fibrillation-related ischemic stroke (n=1,500). Anticoagulation initiation at different time intervals vs. Four arms of time to start anticoagulation (Days 3, 6, 10, 14 for mild/moderate; Days 6, 10, 14, 21 for severe) was evaluated on Composite occurrence of an ischemic or hemorrhagic event within 30 days of the index stroke. The START trial is a prospective, response-adaptive randomized clinical trial designed to enroll 1500 patients to determine the optimal delay time to initiate anticoagulation after ischemic stroke.