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A randomized, multicenter, open-label, blinded end point trial comparing the effects of spironolactone to chlorthalidone on left ventricular mass in patients with early-stage chronic kidney disease: Rationale and design of the SPIRO-CKD trial

Published version
Peer-reviewed

Type

Article

Change log

Authors

Hayer, MK 
Edwards, NC 
Slinn, G 
Moody, WE 
Steeds, RP 

Abstract

Background Chronic kidney disease (CKD) is associated with increased left ventricular (LV) mass and arterial stiffness. In a previous trial, spironolactone improved these end points compared with placebo in subjects with early-stage CKD, but it is not known whether these effects were specific to the drug or secondary to blood pressure lowering. Aim The aim was to investigate the hypothesis that spironolactone is superior to chlorthalidone in the reduction of LV mass while exerting similar effects on blood pressure. Design This is a multicenter, prospective, randomized, open-label, blinded end point clinical trial initially designed to compare the effects of 40 weeks of treatment with spironolactone 25 mg once daily to chlorthalidone 25 mg once daily on the co-primary end points of change in pulse wave velocity and change in LV mass in 350 patients with stages 2 and 3 CKD on established treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Because of slow recruitment rates, it became apparent that it would not be possible to recruit this sample size within the funded time period. The study design was therefore changed to one with a single primary end point of LV mass requiring 150 patients. Recruitment was completed on 31 December 2016, at which time 154 patients had been recruited. Investigations included cardiac magnetic resonance imaging, applanation tonometry, 24-hour ambulatory blood pressure monitoring, and laboratory tests. Subjects are assessed before and after 40 weeks of randomly allocated drug therapy and at 46 weeks after discontinuation of the study drug.

Description

Keywords

Adult, Aged, Chlorthalidone, Dose-Response Relationship, Drug, Drug Therapy, Combination, Female, Follow-Up Studies, Heart Ventricles, Humans, Hypertrophy, Left Ventricular, Kidney Failure, Chronic, Magnetic Resonance Imaging, Cine, Male, Middle Aged, Mineralocorticoid Receptor Antagonists, Prospective Studies, Pulse Wave Analysis, Single-Blind Method, Sodium Chloride Symporter Inhibitors, Spironolactone, Survival Rate, Time Factors, Treatment Outcome, United States, Vascular Stiffness

Journal Title

American Heart Journal

Conference Name

Journal ISSN

0002-8703
1097-6744

Volume Title

191

Publisher

Elsevier
Sponsorship
British Heart Foundation (via University of Birmingham) (RG_13-013)
British Heart Foundation (None)
We acknowledge the assistance and facilities provided by the NIHR/Wellcome Trust Birmingham Clinical Research Facility.