Morrow, Andrew and Young, Robin and Abraham, George R. and Hoole, Stephen and Oliveira, Joana Maria Gomes and Greenwood, John P. and Arnold, Jayanth Ranjit and Ferreira, Vanessa and Rakhit, Roby and Galasko, Gavin and Sinha, Aish and Perera, Divaka and Al-Lamee, Rasha and Spyridopoulos, Ioakim and Kotecha, Ashish and Clesham, Gerald and Ford, Thomas J. and Davenport, Anthony and Padmanabhan, Sandosh and Kaski, Juan Carlos and Weir, Robin A. and Sattar, Naveed and Ambery, Philip and Welsh, Paul and McConnachie, Alex and Berry, Colin (2026) Exercise treadmill testing for efficacy evaluation in randomized, controlled trials. American Heart Journal: 107379. ISSN 0002-8703 (In Press)
Full text not available from this repository.Abstract
Exercise treadmill testing measures functional capacity and inducible myocardial ischemia and has historically served as an endpoint in phase 2 trials. The Precision Medicine with Zibotentan in Microvascular Angina trial evaluated the selective endothelin-A receptor antagonist zibotentan as a potential disease-modifying therapy for microvascular angina. The trial had a randomized, double-blind, cross-over design and the primary outcome was exercise duration. Compared with placebo, zibotentan at a dose of 10-mg daily for 12-weeks did not improve exercise duration or angina symptoms. In this pre-specified analysis, exercise duration was compared across four sequential study visits and the factors associated with within-trial changes were evaluated. Exercise test duration increased progressively in all participants during sequential trial phases, independent of treatment with either zibotentan or placebo. This improvement in exercise duration was associated with female sex (interaction p-value = 0.0213; effect estimate [95% confidence interval]) 34.95 [13.99, 55.78] seconds, p=0.002). In conclusion, the exercise test has limitations as an objective endpoint of efficacy in randomized trials. PRIZE; https://clinicaltrials.gov/study/NCT04097314