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)
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 nifedipin...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
NIHR Journals Library
2015-08-01
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| Series: | Health Technology Assessment |
| Subjects: | |
| Online Access: | https://doi.org/10.3310/hta19630 |
| _version_ | 1828472587437473792 |
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| author | Robert Pickard Kathryn Starr Graeme MacLennan Mary Kilonzo Thomas Lam Ruth 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 |
| author_facet | Robert Pickard Kathryn Starr Graeme MacLennan Mary Kilonzo Thomas Lam Ruth 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 |
| author_sort | Robert Pickard |
| collection | DOAJ |
| description | 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. Objectives: 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. 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 ≤ 10 mm, localised by computerised tomography, who were able to take trial medications and complete trial procedures. Interventions: 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. 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™) 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. Trial registration: Current Controlled Trials ISRCTN69423238. European Clinical Trials Database (EudraCT) number 2010–019469–26. Funding: 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. |
| first_indexed | 2024-12-11T05:32:10Z |
| format | Article |
| id | doaj.art-19169302170a452283b9f275e8b5b2ec |
| institution | Directory Open Access Journal |
| issn | 1366-5278 2046-4924 |
| language | English |
| last_indexed | 2024-12-11T05:32:10Z |
| publishDate | 2015-08-01 |
| publisher | NIHR Journals Library |
| record_format | Article |
| series | Health Technology Assessment |
| spelling | doaj.art-19169302170a452283b9f275e8b5b2ec2022-12-22T01:19:24ZengNIHR Journals LibraryHealth Technology Assessment1366-52782046-49242015-08-01196310.3310/hta1963008/71/01Use 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 Pickard0Kathryn Starr1Graeme MacLennan2Mary Kilonzo3Thomas Lam4Ruth Thomas5Jennifer Burr6John Norrie7Gladys McPherson8Alison McDonald9Kirsty Shearer10Katie Gillies11Kenneth Anson12Charles Boachie13James N’Dow14Neil Burgess15Terry Clark16Sarah Cameron17Samuel McClinton18Institute of Cellular Medicine, Newcastle University, Newcastle, UKHealth Services Research Unit, University of Aberdeen, Aberdeen, UKHealth Services Research Unit, University of Aberdeen, Aberdeen, UKHealth Economics Research Unit, University of Aberdeen, Aberdeen, UKAcademic Urology Unit, University of Aberdeen, Aberdeen, UKHealth Services Research Unit, University of Aberdeen, Aberdeen, UKSchool of Medicine, University of St Andrews, St Andrews, UKHealth Services Research Unit, University of Aberdeen, Aberdeen, UKHealth Services Research Unit, University of Aberdeen, Aberdeen, UKHealth Services Research Unit, University of Aberdeen, Aberdeen, UKHealth Services Research Unit, University of Aberdeen, Aberdeen, UKHealth Services Research Unit, University of Aberdeen, Aberdeen, UKSt George’s Healthcare NHS Trust, London, UKHealth Services Research Unit, University of Aberdeen, Aberdeen, UKAcademic Urology Unit, University of Aberdeen, Aberdeen, UKNorfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UKStone Patient Advisory Group, Section of Endourology, British Association of Urological Surgeons, London, UKHealth Services Research Unit, University of Aberdeen, Aberdeen, UKAcademic Urology Unit, University of Aberdeen, Aberdeen, UKBackground: 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. Objectives: 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. 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 ≤ 10 mm, localised by computerised tomography, who were able to take trial medications and complete trial procedures. Interventions: 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. 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™) 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. Trial registration: Current Controlled Trials ISRCTN69423238. European Clinical Trials Database (EudraCT) number 2010–019469–26. Funding: 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.https://doi.org/10.3310/hta19630drug therapyureteric stonesrandomised controlled trialcalcium channel blockernifedipinealpha-blockertamsulosin |
| spellingShingle | Robert Pickard Kathryn Starr Graeme MacLennan Mary Kilonzo Thomas Lam Ruth 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 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) Health Technology Assessment drug therapy ureteric stones randomised controlled trial calcium channel blocker nifedipine alpha-blocker tamsulosin |
| 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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 |
| topic | drug therapy ureteric stones randomised controlled trial calcium channel blocker nifedipine alpha-blocker tamsulosin |
| url | https://doi.org/10.3310/hta19630 |
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