title: Use of drug therapy in the management of symptomatic ureteric stones in hospitalised adults: a multicentre, placebo-controlled, randomised controlled trial and cost-effectiveness analysis of a calcium channel blocker (nifedipine) and an alpha-blocker (tamsulosin) (the SUSPEND trial).
abstract: BACKGROUND
  Ureteric colic, the term used to describe the pain felt when a stone passes down the ureter from the kidney to the bladder, is a frequent reason for people to seek emergency health care. Treatment with the muscle-relaxant drugs tamsulosin hydrochloride (Petyme, TEVA UK Ltd) and nifedipine (Coracten(®), UCB Pharma Ltd) as medical expulsive therapy (MET) is increasingly being used to improve the likelihood of spontaneous stone passage and lessen the need for interventional procedures. However, there remains considerable uncertainty around the effectiveness of these drugs for routine use.
  
  
  OBJECTIVE
  To determine whether or not treatment with either tamsulosin 400 µg or nifedipine 30 mg for up to 4 weeks increases the rate of spontaneous stone passage for people with ureteric colic compared with placebo, and whether or not it is cost-effective for the UK NHS.
  
  
  METHODS
  A pragmatic, randomised controlled trial comparing two active drugs, tamsulosin and nifedipine, against placebo. Participants, clinicians and trial staff were blinded to treatment allocation. A cost-utility analysis was performed using data gathered during trial participation.
  
  
  METHODS
  Urology departments in 24 UK NHS hospitals.
  
  
  METHODS
  Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuring ≤ 10 mm, localised by computerised tomography, who were able to take trial medications and complete trial procedures.
  
  
  METHODS
  Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 µg, nifedipine 30 mg or placebo once daily for up to 4 weeks to make the following comparisons: tamsulosin or nifedipine (MET) versus placebo and tamsulosin versus nifedipine.
  
  
  METHODS
  The primary effectiveness outcome was the proportion of participants who spontaneously passed their stone. This was defined as the lack of need for active intervention for ureteric stones at up to 4 weeks after randomisation. This was determined from 4- and 12-week case-report forms completed by research staff, and from the 4-week participant self-reported questionnaire. The primary economic outcome was the incremental cost per quality-adjusted life-year (QALY) gained over 12 weeks. We estimated costs from NHS sources and calculated QALYs from participant completion of the European Quality of Life-5 Dimensions health status questionnaire 3-level response (EQ-5D-3L™) at baseline, 4 weeks and 12 weeks.
  
  
  RESULTS
  Primary outcome analysis included 97% of the 1167 participants randomised (378/391 tamsulosin, 379/387 nifedipine and 379/399 placebo participants). The proportion of participants who spontaneously passed their stone did not differ between MET and placebo [odds ratio (OR) 1.04, 95% confidence interval (CI) 0.77 to 1.43; absolute difference 0.8%, 95% CI -4.1% to 5.7%] or between tamsulosin and nifedipine [OR 1.06, 95% CI 0.74 to 1.53; absolute difference 1%, 95% CI -4.6% to 6.6%]. There was no evidence of a difference in QALYs gained or in cost between the trial groups, which means that the use of MET would be very unlikely to be considered cost-effective. These findings were unchanged by extensive sensitivity analyses around predictors of stone passage, including sex, stone size and stone location.
  
  
  CONCLUSIONS
  Tamsulosin and nifedipine did not increase the likelihood of stone passage over 4 weeks for people with ureteric colic, and use of these drugs is very unlikely to be cost-effective for the NHS. Further work is required to investigate the phenomenon of large, high-quality trials showing smaller effect size than meta-analysis of several small, lower-quality studies.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN69423238. European Clinical Trials Database (EudraCT) number 2010-019469-26.
  
  
  BACKGROUND
  This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 63. See the NIHR Journals Library website for further project information.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Pickard
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Starr
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Graeme
authors.initials: G
authors.lastname: MacLennan
authors.affiliation: Health Economics Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Mary
authors.initials: M
authors.lastname: Kilonzo
authors.affiliation: Academic Urology Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lam
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Thomas
authors.affiliation: School of Medicine, University of St Andrews, St Andrews, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Burr
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: John
authors.initials: J
authors.lastname: Norrie
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Gladys
authors.initials: G
authors.lastname: McPherson
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: McDonald
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Shearer
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Gillies
authors.affiliation: St George's Healthcare NHS Trust, London, UK.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Anson
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Boachie
authors.affiliation: Academic Urology Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: James
authors.initials: J
authors.lastname: N'Dow
authors.affiliation: Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Burgess
authors.affiliation: Stone Patient Advisory Group, Section of Endourology, British Association of Urological Surgeons, London, UK.
authors.forename: Terry
authors.initials: T
authors.lastname: Clark
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cameron
authors.affiliation: Academic Urology Unit, University of Aberdeen, Aberdeen, UK.|Aberdeen Royal Infirmary, Foresterhill, Aberdeen, UK.
authors.forename: Samuel
authors.initials: S
authors.lastname: McClinton
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000328:Adult; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D010146:Pain / Q000209:etiology; D011788:Quality of Life; D013222:State Medicine; D013449:Sulfonamides / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000077409:Tamsulosin; D006113:United Kingdom; D014545:Urinary Calculi / Q000150:complications / Q000188:drug therapy*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D002121:Calcium Channel Blockers; D013449:Sulfonamides; D000077409:Tamsulosin; D009543:Nifedipine