Abstract Body: Background:
Clinical trial designs have evolved due to changes in therapies, populations, and statistical methods.
Objective:
We aimed to analyze the designs of acute endovascular therapy trials in ischemic stroke over time, and how mechanical thrombectomy has evolved, particularly in patient selection and statistical methods.
Methods:
A systematic search was conducted in PubMed, EMBASE, Cochrane, CINAHL, and SCOPUS for phase 3 or 4 randomized clinical trials of endovascular reperfusion therapy for acute ischemic stroke. Trials with functional outcomes measured at 3 months were included. Data extracted included year of publication, estimated and actual sample sizes, observed outcomes, and statistical methods used. The studies were classified in 3 periods by publication date: Period 1: before 2015, pre-stent retriever; Period 2: 2015-2019, early thrombectomy era; and Period 3: 2020-2024, recent period.
Results:
Of 2693 references, 21 trials met inclusion criteria, 3 in Period 1, 10 in Period 2, 8 in Period 3. Median sample sizes were 150 in Period 1, 206 in Period 2, and 300 in Period 3. Dichotomized Rankin were primary outcomes in 100% in Period 1, 80% in Period 2, and 60% in Period 3, with remainder analyzed by Rankin shift or proportional odds. Early termination occurred in 0% in Period 1, 40% in Period 2, and 0% in Period 3. 7 studies met or almost met their estimated sample size.14 studies did not meet their estimated sample size, due to early terminations (for efficacy or futility), slow recruitment, or positive findings from other trials
Conclusion:
The trials published during the 2015–2019 period had early terminations and positive results for thrombectomy. More recent trials have larger sample sizes and more commonly used methods to analyze the full range of Rankin categories, such as mRS shift or proportional odds models. This might reflect a shift toward capturing more nuanced outcomes in stroke populations.