title: 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
  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.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN80658312.
authors.forename: Khai P
authors.initials: KP
authors.lastname: Ng
authors.forename: Poorva
authors.initials: P
authors.lastname: Jain
authors.forename: Gurdip
authors.initials: G
authors.lastname: Heer
authors.forename: Val
authors.initials: V
authors.lastname: Redman
authors.forename: Odette L
authors.initials: OL
authors.lastname: Chagoury
authors.forename: George
authors.initials: G
authors.lastname: Dowswell
authors.forename: Sheila
authors.initials: S
authors.lastname: Greenfield
authors.forename: Nick
authors.initials: N
authors.lastname: Freemantle
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Townend
authors.forename: Paramjit S
authors.initials: PS
authors.lastname: Gill
authors.forename: Richard J
authors.initials: RJ
authors.lastname: McManus
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham B15 2WB, UK. charles.ferro@uhb.nhs.uk.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ferro
mesh_terms: D001291:Attitude of Health Personnel; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002985:Clinical Protocols; D004311:Double-Blind Method; D042241:Early Diagnosis; D004739:England; D058005:General Practitioners / Q000523:psychology; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D006947:Hyperkalemia / Q000097:blood / Q000139:chemically induced; D007676:Kidney Failure, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D011188:Potassium / Q000097:blood; D011237:Predictive Value of Tests; D011320:Primary Health Care; D011446:Prospective Studies; D063177:Pulse Wave Analysis; D036301:Qualitative Research; D012107:Research Design; D013148:Spironolactone / Q000009:adverse effects / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects
chemical_list: D015415:Biomarkers; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D011188:Potassium