RT Journal Article
SR 00
ID 10.1016/j.ahj.2020.07.007
A1 Morrow, Andrew J.
A1 Ford, Thomas J.
A1 Mangion, Kenneth
A1 Kotecha, Tushar
A1 Rakhit, Roby
A1 Galasko, Gavin
A1 Hoole, Stephen
A1 Davenport, Anthony
A1 Kharbanda, Rajesh
A1 Ferreira, Vanessa M.
A1 Shanmuganathan, Mayooran
A1 Chiribiri, Amedeo
A1 Perera, Divaka
A1 Rahman, Haseeb
A1 Arnold, Jayanth R.
A1 Greenwood, John P.
A1 Fisher, Michael
A1 Husmeier, Dirk
A1 Hill, Nicholas A.
A1 Luo, Xiaoyu
A1 Williams, Nicola
A1 Miller, Laura
A1 Dempster, Jill
A1 Macfarlane, Peter W.
A1 Welsh, Paul
A1 Sattar, Naveed
A1 Whittaker, Andrew
A1 McConnachie, Alex
A1 Padmanabhan, Sandosh
A1 Berry, Colin
T1 Rationale and design of the Medical Research Council precision medicine with Zibotentan in microvascular angina (PRIZE) trial
JF American Heart Journal
YR 2020
FD 2020-11
VO 229
SP 70
OP 80
AB Background:   Microvascular angina is caused by cardiac small vessel disease and dysregulation of the endothelin system is implicated. The minor G allele of the non-coding single nucleotide polymorphism (SNP) rs9349379 enhances expression of the endothelin 1 gene in human vascular cells, increasing circulating concentrations of ET-1. The prevalence of this allele is higher in patients with ischemic heart disease. Zibotentan is a potent, selective inhibitor of the ETA receptor. We have identified zibotentan as a potential disease-modifying therapy for patients with microvascular angina.    Methods:   We will assess the efficacy and safety of adjunctive treatment with oral zibotentan (10 mg daily) in patients with microvascular angina and assess whether rs9349379 (minor G allele; population prevalence ~36%) acts as a theragnostic biomarker of the response to treatment with zibotentan.    The Precision medicine with Zibotentan in microvascular angina (PRIZE) trial is a prospective, randomized, double-blind, placebo-controlled, sequential cross-over trial. The study population will be enriched to ensure a G-allele frequency of 50% for the rs9349379 SNP. The participants will receive a single-blind placebo run-in followed by treatment with either 10 mg of zibotentan daily for 12 weeks then placebo for 12 weeks, or vice versa, in random order. The primary outcome is treadmill exercise duration using the Bruce protocol. The primary analysis will assess the within-subject difference in exercise duration following treatment with zibotentan versus placebo.    Conclusion:   PRIZE invokes precision medicine in microvascular angina. Should our hypotheses be confirmed, this developmental trial will inform the rationale and design for undertaking a larger multicenter trial.
PB Elsevier
SN 0002-8703
LK https://eprints.gla.ac.uk/220997/