Spironolactone to prevent cardiovascular events in early-stage chronic kidney
disease (STOP-CKD): study protocol for a randomized controlled pilot trial.
Author(s): Ng KP, Jain P, Heer G, Redman V, Chagoury OL, Dowswell G, Greenfield S,
Freemantle N, Townend JN, Gill PS, McManus RJ, Ferro CJ(1).
Affiliation(s): Author information:
(1)Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Mindelsohn
Way, Birmingham B15 2WB, UK. charles.ferro@uhb.nhs.uk.
Publication date & source: 2014, Trials. , 15:158
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.
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