Dataset Information

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

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.

SUBMITTER: Ng KP

PROVIDER: S-EPMC4113230 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Ng Khai P KP Jain Poorva P Heer Gurdip G Redman Val V Chagoury Odette L OL Dowswell George G Greenfield Sheila S Freemantle Nick N Townend Jonathan N JN Gill Paramjit S PS McManus Richard J RJ Ferro Charles J CJ

Trials 20140506

<h4>Background</h4>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 majorit ...[more]

PMID: 24886272

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Project description:Soluble TNF-like weak inducer of apoptosis (sTWEAK) is a proinflammatory cytokine belonging to the TNF superfamily. sTWEAK concentrations have been associated with the presence of CKD and cardiovascular disease (CVD). We hypothesized that sTWEAK levels may relate to a higher prevalence of atherosclerotic plaques, vascular calcification, and cardiovascular outcomes observed in patients with CKD.A 4-year prospective, multicenter, longitudinal study was conducted in 1058 patients with CKD stages 3-5D (mean age =58±13 years old; 665 men) but without any history of CVD from the NEFRONA Study (a study design on the prevalence of surrogate markers of CVD). Ankle-brachial index and B-mode ultrasound were performed to detect the presence of carotid and/or femoral atherosclerotic plaques together with biochemical measurements and sTWEAK assessment. Patients were followed for cardiovascular outcomes (follow-up of 3.13±1.15 years).Patients with more advanced CKD had lower sTWEAK levels. sTWEAK concentrations were independently and negatively associated with carotid intima-media thickness. sTWEAK levels were lower in patients with carotid atherosclerotic plaques but not in those with femoral plaques. After adjustment by confounders, the odds ratio (OR) for presenting carotid atherosclerotic plaques in patients in the lowest versus highest tertile of sTWEAK was 4.18 (95% confidence interval [95% CI], 2.89 to 6.08; P<0.001). Furthermore, sTWEAK levels were lower in patients with calcified carotid atherosclerotic plaques. The OR for presenting calcified carotid plaques was 1.77 (95% CI, 1.06 to 2.93; P=0.02) after multivariable adjustment. After the follow-up, 41 fatal and 68 nonfatal cardiovascular events occurred. In a Cox model, after controlling for potential confounding factors, patients in the lowest tertile of sTWEAK concentrations had a higher risk of fatal and nonfatal cardiovascular events (hazard ratio [HR], 2.40; 95% CI, 1.33 to 4.33; P=0.004) and cardiovascular mortality (HR, 2.67; 95% CI, 1.05 to 6.76; P=0.04).Low sTWEAK levels were associated with the presence of carotid atherosclerotic plaques in patients with CKD. Additionally, lower sTWEAK levels were associated with a higher risk of cardiovascular morbidity and mortality.

Dataset Information

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

Background

Methods/design

Trial registration

Publications

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

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