Study Design and Participants
The TRUST trial was a prospective, open-label, randomized, blinded-endpoint, multicenter study conducted in China from October 4, 2020, to November 11, 2022. It aimed to evaluate the efficacy and safety of intravenous UK administered within 6 hours of symptom onset for acute ischemic stroke patients with a National Institutes of Health Stroke Scale (NIHSS) score of 0–5. Patients aged 18–80 years, experiencing their first stroke or with a pre-stroke modified Rankin scale (mRS) score ≤1, were eligible. The study excluded patients with lesions larger than 1/3 middle cerebral artery territory, intracranial hemorrhage, or other contraindications.
Randomization and Treatment
Patients were randomly assigned in a 1:1 ratio to receive either UK intravenous thrombolysis or guideline-based best medicine treatment. The UK group received 1,000,000 U UK dissolved in 100 mL of saline via continuous intravenous infusion for 30 minutes, within 6 hours of stroke onset. The best medicine treatment group received antithrombotic treatments as per local investigator's discretion.
Outcomes
The primary outcome was an excellent functional outcome, defined as an mRS score of 0–1 at 90 days. Secondary outcomes included new clinical vascular events, functional disability, health-related quality of life, and Barthel Index score ≥95 at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) within 36 hours post-randomization.
Statistical Analysis
The study aimed to detect a 6.5% difference in the primary outcome between the UK and control groups, requiring 1002 subjects. Statistical analyses were conducted using SAS (version 9.4), with two-sided p values less than 0.05 considered statistically significant. The analysis adjusted for covariates such as age, gender, baseline NIHSS score, systolic blood pressure, and myocardial infarction.
Conclusion
The TRUST trial provides valuable insights into the potential benefits and risks of intravenous UK for acute ischemic stroke patients, emphasizing the need for timely treatment and careful patient selection to optimize outcomes and minimize risks.
