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Open Access Study protocol

Spironolactone to prevent cardiovascular events in early-stage chronic kidney disease (STOP-CKD): study protocol for a randomized controlled pilot trial

Khai P Ng1, Poorva Jain2, Gurdip Heer2, Val Redman2, Odette L Chagoury2, George Dowswell2, Sheila Greenfield2, Nick Freemantle3, Jonathan N Townend4, Paramjit S Gill2, Richard J McManus5 and Charles J Ferro1*

Author Affiliations

1 Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham B15 2WB, UK

2 Primary Care Clinical Sciences, School of Health and Population Sciences, University of Birmingham, Birmingham B15 2TT, UK

3 Department of Primary Care and Population Health, UCL Medical School, Rowland Hill Street, London NW3 2PF, UK

4 Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham B15 2WB, UK

5 Department of Primary Care Health Sciences, University of Oxford, 2nd Floor, 23-38 Hythe Bridge Street, Oxford OX1 2ET, UK

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Trials 2014, 15:158  doi:10.1186/1745-6215-15-158

Published: 6 May 2014

Abstract

Background

Chronic kidney disease is associated with increased arterial stiffness even in the early stages and this is thought to be a key mediator in the pathophysiology of the increased cardiovascular risk associated with this condition. The use of low-dose spironolactone has previously been shown to improve arterial stiffness and reduce left ventricular mass safely in early-stage chronic kidney disease in the context of careful monitoring at a university hospital. However, the majority of patients with chronic kidney disease are managed by their general practitioners in the community. It is not known whether similar beneficial effects can be achieved safely using spironolactone in the primary care setting. The aim of this study is to determine whether low-dose spironolactone can safely lower arterial stiffness in patients with stage 3 chronic kidney disease in the primary care setting.

Methods/design

STOP-CKD is a multicentre, prospective, randomized, double-blind, placebo-controlled pilot trial of 240 adult patients with stage 3 chronic kidney disease recruited from up to 20 general practices in South Birmingham, England. Participants will be randomly allocated using a secured web-based computer randomization system to receive either spironolactone 25 mg once daily or a matching inactive placebo for 40 weeks, followed by a wash-out period of 6 weeks. Investigators, outcome assessors, data analysts and participants will all be blinded to the treatment allocation. The primary endpoint is improved arterial stiffness, as measured by carotid-femoral pulse wave velocity between baseline and 40 weeks. The secondary endpoints are incidence of hyperkalaemia, change in estimated glomerular filtration rate, change in urine albumin:creatinine ratio, change in brachial blood pressure, change in pulse waveform characteristics and overall tolerability of spironolactone. An additional quality control study, aiming to compare the laboratory serum potassium results of samples processed via two methods (utilizing routine transport or centrifugation on site before rapid transport to the laboratory) for 100 participants and a qualitative research study exploring patients’ and general practitioners’ attitudes to research and the use of spironolactone in chronic kidney disease in the community setting will be embedded in this pilot study.

Trial registration

Current Controlled Trials ISRCTN80658312.

Keywords:
arterial stiffness; cardiovascular events; chronic kidney disease; feasibility; mineralocorticoid receptor antagonist; pulse wave velocity; qualitative; randomized controlled trial; renal dysfunction; spironolactone