TY  - JOUR
ID  - enlighten220997
UR  - https://eprints.gla.ac.uk/220997/
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
Y1  - 2020/11//
N2  - 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
JF  - American Heart Journal
VL  - 229
SN  - 0002-8703
TI  - Rationale and design of the Medical Research Council precision medicine with Zibotentan in microvascular angina (PRIZE) trial
SP  - 70
AV  - public
EP  - 80
ER  -