Title: Spironolactone to Prevent Cardiovascular Events in Early Stage CKD (STOP CKD). A pilot trial
Funder: Department of Health (England)

Abstract: Background Stage 3 chronic kidney disease (CKD3) (GFR 30-59 ml/min/1.73m2) is common in primary care with a prevalence of around 10%. Patients have an increased risk of cardiovascular disease but current evidence for treatment is poor. Mineralocorticoid receptor blocker (MRB) therapy might be effective as aldosterone exerts powerful inflammatory and hypertrophic effects on the cardiovascular system. We have shown in a double blind, prospective, placebo controlled trial that spironolactone, a cheap MRB, improves arterial stiffness and left ventricular mass and function in a hospital population. This suggests that this drug may reduce cardiovascular events in people with CKD3 but before it can be trialled on a larger scale, evidence of the feasibility and safety of its use in primary care is needed. Aims Previously we examined the impact of spironolactone in patients with CKD recruited in a specialist setting and found benefits in terms of intermediate outcomes. Prior to a larger trial, further feasibility work is required to test procedures and outcomes in a primary care setting. This pilot study will answer the following questions: 1) What are patient and professionals’ attitudes to spironolactone in CKD in a community setting and what potential barriers exist to its use? 2) What is the recruitment rate to the trial? 3) Are similar effects on arterial stiffness measured, by pulse wave velocity, achievable in primary care? 4) What rates of hyperkalaemia are seen in primary care and how are these affected by the method of analysis? Plan of Investigation A pilot trial will recruit subjects with CKD3 from General Practices within the Birmingham area and will have a standardised assessment at baseline. Patients will be randomised and stratified by practice and baseline blood pressure to spironolactone versus placebo. Both groups will be titrated to standard blood pressure targets. Biochemical renal function and blood pressure will be checked throughout the study. After forty weeks, participants will undergo repeat assessment. Outcomes will include pulse wave velocity, changes in blood pressure and incidence of side effects during the trial. Preliminary qualitative interviews with patients and primary care professionals will explore attitudes towards the trial and design issues. Potential Impact The cardiovascular risk of patients with stage 3 CKD is high at 2-4 times that of control populations and much more likely to impact on patients’ lives than progression to renal failure. No prospective interventional trial examining hard clinical end points has evaluated treatments to reduce this risk. The effects of MRB therapy are very promising but require confirmation in the population where use would be most likely. This pilot study is designed to gain this information prior to a large multi-centre trial with clinical end points. Ultimately, the goal is a low cost, low risk treatment that would result in a highly cost effective reduction of the rate of stroke, heart failure and sudden cardiac death in patients with CKD.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CARDIOVASCULAR;RENAL AND UROGENITAL