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)

Robert Pickard, Kathryn Starr, Graeme MacLennan, Mary Kilonzo, Thomas Lam, Ruth Elizabeth Thomas, Jennifer Burr, John Norrie, Gladys McPherson, Alison McDonald, Kirsty Shearer, Katie Gillies, Kenneth Anson, Charles Boachie, James N'Dow, Neil Burgess, Terry Clark, Sarah Cameron, Samuel McClinton*

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Citations (Scopus)
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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 (R), 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.

Objectives: To determine whether or not treatment with either tamsulosin 400 mu g 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.

Design: 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.

Setting: Urology departments in 24 UK NHS hospitals.

Participants: Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuring

Interventions: Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 mu g, 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.

Main outcome measures: 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 (TM)) 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.

Original languageEnglish
Number of pages195
JournalHealth Technology Assessment
Volume19
Issue number63
DOIs
Publication statusPublished - Aug 2015

Keywords

  • upper urinary-tract
  • smooth-muscle
  • medical therapy
  • emergency-department
  • induced activation
  • United-States
  • in-vitro
  • calculi
  • metaanalysis
  • facilitate

Cite this

@article{da35ac535df442509a70b59474e87359,
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 (R), 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.Objectives: To determine whether or not treatment with either tamsulosin 400 mu g 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.Design: 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.Setting: Urology departments in 24 UK NHS hospitals.Participants: Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuringInterventions: Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 mu g, 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.Main outcome measures: 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 (TM)) 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.",
keywords = "upper urinary-tract, smooth-muscle, medical therapy, emergency-department, induced activation, United-States, in-vitro, calculi, metaanalysis , facilitate",
author = "Robert Pickard and Kathryn Starr and Graeme MacLennan and Mary Kilonzo and Thomas Lam and Thomas, {Ruth Elizabeth} and Jennifer Burr and John Norrie and Gladys McPherson and Alison McDonald and Kirsty Shearer and Katie Gillies and Kenneth Anson and Charles Boachie and James N'Dow and Neil Burgess and Terry Clark and Sarah Cameron and Samuel McClinton",
note = "Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme",
year = "2015",
month = "8",
doi = "10.3310/hta19630",
language = "English",
volume = "19",
journal = "Health Technology Assessment",
issn = "1366-5278",
publisher = "National Co-ordinating Centre for HTA",
number = "63",

}

TY - JOUR

T1 - Use of drug therapy in the management of symptomatic ureteric stones in hospitalised adults

T2 - 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)

AU - Pickard, Robert

AU - Starr, Kathryn

AU - MacLennan, Graeme

AU - Kilonzo, Mary

AU - Lam, Thomas

AU - Thomas, Ruth Elizabeth

AU - Burr, Jennifer

AU - Norrie, John

AU - McPherson, Gladys

AU - McDonald, Alison

AU - Shearer, Kirsty

AU - Gillies, Katie

AU - Anson, Kenneth

AU - Boachie, Charles

AU - N'Dow, James

AU - Burgess, Neil

AU - Clark, Terry

AU - Cameron, Sarah

AU - McClinton, Samuel

N1 - Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme

PY - 2015/8

Y1 - 2015/8

N2 - 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 (R), 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.Objectives: To determine whether or not treatment with either tamsulosin 400 mu g 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.Design: 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.Setting: Urology departments in 24 UK NHS hospitals.Participants: Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuringInterventions: Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 mu g, 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.Main outcome measures: 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 (TM)) 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.

AB - 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 (R), 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.Objectives: To determine whether or not treatment with either tamsulosin 400 mu g 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.Design: 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.Setting: Urology departments in 24 UK NHS hospitals.Participants: Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuringInterventions: Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 mu g, 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.Main outcome measures: 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 (TM)) 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.

KW - upper urinary-tract

KW - smooth-muscle

KW - medical therapy

KW - emergency-department

KW - induced activation

KW - United-States

KW - in-vitro

KW - calculi

KW - metaanalysis

KW - facilitate

U2 - 10.3310/hta19630

DO - 10.3310/hta19630

M3 - Article

VL - 19

JO - Health Technology Assessment

JF - Health Technology Assessment

SN - 1366-5278

IS - 63

ER -