Results and lessons from the Spironolactone To Prevent Cardiovascular Events in Early Stage Chronic Kidney Disease (STOP-CKD) randomised controlled trial

BMJ Open 2016;6:e010519 doi:10.1136/bmjopen-2015-010519 Renal medicine Results and lessons from the Spironolactone To Prevent Cardiovascular Events in Early Stage Chronic Kidney Disease (STOP-CKD) randomised controlled trial Khai P Ng1, Poorva Jain2, Paramjit S Gill2, Gurdip Heer2, Jonathan N Townend3, Nick Freemantle4, Sheila Greenfield2, Richard J McManus5, Charles J Ferro1 + Author Affiliations 1Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK 2Department of Primary Care Clinical Sciences, School of Health and Population Sciences, University of Birmingham, Birmingham, UK 3Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, UK 4Department of Primary Care and Population Health, UCL Medical School, London, UK 5Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK Correspondence to Dr Charles Ferro; charles.ferro@uhb.nhs.uk Received 10 November 2015 Revised 5 January 2016 Accepted 1 February 2016 Published 25 February 2016 Abstract Objectives To determine whether low-dose spironolactone can safely lower arterial stiffness in patients with chronic kidney disease stage 3 in the primary care setting. Design A multicentre, prospective, randomised, placebo-controlled, double-blinded study. Setting 11 primary care centres in South Birmingham, England. Participants Adult patients with stage 3 chronic kidney disease. Main exclusion criteria were diagnosis of diabetes mellitus, chronic heart failure, atrial fibrillation, severe hypertension, systolic blood pressure <120 mm Hg or baseline serum potassium ≥5 mmol/L. Intervention Eligible participants were randomised to receive either spironolactone 25 mg once daily, or matching placebo for an intended period of 40 weeks. Outcome measures The primary end point was the change in arterial stiffness as measured by pulse wave velocity. Secondary outcome measures included the rate of hyperkalaemia, deterioration of renal function, barriers to participation and expected recruitment rates to a potential future hard end point study. Results From the 11 practices serving a population of 112 462, there were 1598 (1.4%) patients identified as being eligible and were invited to participate. Of these, 134 (8.4%) attended the screening visit of which only 16 (1.0%) were eligible for randomisation. The main reasons for exclusion were low systolic blood pressure (<120 mm Hg: 40 patients) and high estimated glomerular filtration rate (≥60 mL/min/1.73 m2: 38 patients). The trial was considered unfeasible and was terminated early. Conclusions We highlight some of the challenges in undertaking research in primary care including patient participation in trials. This study not only challenged our preconceptions, but also provided important learning for future research in this large and important group of patients. Trial registration number ISRCTN80658312.