title: Results and lessons from the Spironolactone To Prevent Cardiovascular Events in Early Stage Chronic Kidney Disease (STOP-CKD) randomised controlled trial.
abstract: OBJECTIVE
  To determine whether low-dose spironolactone can safely lower arterial stiffness in patients with chronic kidney disease stage 3 in the primary care setting.
  
  
  METHODS
  A multicentre, prospective, randomised, placebo-controlled, double-blinded study.
  
  
  METHODS
  11 primary care centres in South Birmingham, England.
  
  
  METHODS
  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.
  
  
  METHODS
  Eligible participants were randomised to receive either spironolactone 25 mg once daily, or matching placebo for an intended period of 40 weeks.
  
  
  METHODS
  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 m(2): 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.
  
  
  BACKGROUND
  ISRCTN80658312.
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
authors.forename: Khai P
authors.initials: KP
authors.lastname: Ng
authors.affiliation: Department of Primary Care Clinical Sciences, School of Health and Population Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Poorva
authors.initials: P
authors.lastname: Jain
authors.affiliation: Department of Primary Care Clinical Sciences, School of Health and Population Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Paramjit S
authors.initials: PS
authors.lastname: Gill
authors.affiliation: Department of Primary Care Clinical Sciences, School of Health and Population Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Gurdip
authors.initials: G
authors.lastname: Heer
authors.affiliation: Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Townend
authors.affiliation: Department of Primary Care and Population Health, UCL Medical School, London, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Freemantle
authors.affiliation: Department of Primary Care Clinical Sciences, School of Health and Population Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Sheila
authors.initials: S
authors.lastname: Greenfield
authors.affiliation: Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Richard J
authors.identifier: http://orcid.org/0000-0003-3638-028X
authors.initials: RJ
authors.lastname: McManus
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ferro
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000517:prevention & control*; D004311:Double-Blind Method; D004739:England; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D013148:Spironolactone / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone
keywords: PRIMARY CARE; cardiovascular; chronic kidney disease; mineralocorticoid receptor antagonist; randomised trial; research recruitment