Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial

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

doi:10.1016/S0140-6736(15)60933-3

Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

257 Citations (Scopus)

11 Downloads (Pure)

Abstract

Background

Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting.

Methods

For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18–65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 μg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238.

Findings

Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI −5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [–5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain).

Interpretation

Tamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic.

Funding

UK National Institute for Health Research Health Technology Assessment Programme.

Original language	English
Pages (from-to)	341-349
Number of pages	9
Journal	The Lancet
Volume	386
Issue number	9991
Early online date	18 May 2015
DOIs	https://doi.org/10.1016/S0140-6736(15)60933-3
Publication status	Published - 25 Jul 2015

Bibliographical note

Acknowledgments

Special thanks must go to all of the SUSPEND trial participants and staff at each of our recruiting centres for taking part in this trial. We thank our collaborators at the SUSPEND sites, and participating National Health Service (NHS) trusts and boards (NHS Grampian, Plymouth Hospitals NHS Trust, The Newcastle upon Tyne Hospitals NHS Foundation Trust, NHS Highland, South Tees Hospitals NHS Foundation Trust, City Hospitals Sunderland NHS Foundation Trust, The Leeds Teaching Hospitals NHS Trust, North Bristol NHS Trust, University Hospitals Bristol NHS Trust, Norfolk and Norwich University Hospitals NHS Foundation Trust, The Royal Liverpool and Broadgreen University Hospitals NHS Trust, NHS Lothian, Guy's and St Thomas' NHS Foundation Trust, St George's Healthcare NHS Trust, Abertawe Bro Morgannwg University Health Board, Mid Yorkshire Hospitals NHS Trust, South Devon Healthcare NHS Foundation Trust, Sheffield Teaching Hospitals NHS Foundation Trust, Cambridge University Hospitals NHS Foundation Trust, Gloucestershire Hospitals NHS Foundation Trust, University Hospitals Birmingham NHS Foundation Trust, Central Manchester University Hospitals NHS Foundation Trust, Southampton University Hospitals NHS Trust, and The University Hospital of South Manchester NHS Foundation Trust). We thank the staff at the SUSPEND trial office based in the Centre for Healthcare Randomised Trials (CHaRT) within the Health Services Research Unit, University of Aberdeen. This report presents independent research funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme, Project Number 08/71/01. The views and opinions expressed in this report are those of the authors and do not necessarily reflect those of the HTA Programme, the NIHR, the NHS, or the Department of Health. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates; however, the opinions expressed in this publication are those of the authors, and might not be shared by the Chief Scientist Office.

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Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial
© Pickard et al. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Final published version, 483 KBLicence: CC BY

Kate Gillies
- School of Medicine, Medical Sciences & Nutrition, Health Services Research Unit (HSRU) - Personal Chair
- Institute of Applied Health Sciences
Person: Academic, Academic Related - Research
Mary Kilonzo
- School of Medicine, Medical Sciences & Nutrition, Health Economics Research Unit - Research Fellow
Person: Academic Related - Research
Thomas Lam
- School of Medicine, Medical Sciences & Nutrition, Applied Health Sciences - Honorary Senior Lecturer
- Institute of Applied Health Sciences
- Academic Urology Unit
Person: Honorary

Cite this

Pickard, R., Starr, K., MacLennan, G., Lam, T. B. L., Thomas, R., Burr, J., McPherson, G., McDonald, A., Anson, K., N'Dow, J., Burgess, N., Clark, T., Kilonzo, M., Gillies, K., Shearer, K., Boachie, C., Cameron, S., Norrie, J., & McClinton, S. (2015). Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. The Lancet, 386(9991), 341-349. https://doi.org/10.1016/S0140-6736(15)60933-3

Pickard, R, Starr, K, MacLennan, G , Lam, TBL , Thomas, R, Burr, J, McPherson, G, McDonald, A, Anson, K, N'Dow, J, Burgess, N, Clark, T, Kilonzo, M , Gillies, K, Shearer, K, Boachie, C, Cameron, S, Norrie, J & McClinton, S 2015, 'Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial', The Lancet, vol. 386, no. 9991, pp. 341-349. https://doi.org/10.1016/S0140-6736(15)60933-3

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title = "Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial",

abstract = "BackgroundMeta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting.MethodsFor this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18–65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 μg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238.FindingsBetween Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI −5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [–5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain).InterpretationTamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic.FundingUK National Institute for Health Research Health Technology Assessment Programme.",

author = "Robert Pickard and Kathryn Starr and Graeme MacLennan and Lam, {Thomas Boon Leong} and Ruth Thomas and Jennifer Burr and Gladys McPherson and Alison McDonald and Kenneth Anson and James N'Dow and Neil Burgess and Terry Clark and Mary Kilonzo and Kate Gillies and Kirsty Shearer and Charles Boachie and Sarah Cameron and John Norrie and Samuel McClinton",

note = "Acknowledgments Special thanks must go to all of the SUSPEND trial participants and staff at each of our recruiting centres for taking part in this trial. We thank our collaborators at the SUSPEND sites, and participating National Health Service (NHS) trusts and boards (NHS Grampian, Plymouth Hospitals NHS Trust, The Newcastle upon Tyne Hospitals NHS Foundation Trust, NHS Highland, South Tees Hospitals NHS Foundation Trust, City Hospitals Sunderland NHS Foundation Trust, The Leeds Teaching Hospitals NHS Trust, North Bristol NHS Trust, University Hospitals Bristol NHS Trust, Norfolk and Norwich University Hospitals NHS Foundation Trust, The Royal Liverpool and Broadgreen University Hospitals NHS Trust, NHS Lothian, Guy's and St Thomas' NHS Foundation Trust, St George's Healthcare NHS Trust, Abertawe Bro Morgannwg University Health Board, Mid Yorkshire Hospitals NHS Trust, South Devon Healthcare NHS Foundation Trust, Sheffield Teaching Hospitals NHS Foundation Trust, Cambridge University Hospitals NHS Foundation Trust, Gloucestershire Hospitals NHS Foundation Trust, University Hospitals Birmingham NHS Foundation Trust, Central Manchester University Hospitals NHS Foundation Trust, Southampton University Hospitals NHS Trust, and The University Hospital of South Manchester NHS Foundation Trust). We thank the staff at the SUSPEND trial office based in the Centre for Healthcare Randomised Trials (CHaRT) within the Health Services Research Unit, University of Aberdeen. This report presents independent research funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme, Project Number 08/71/01. The views and opinions expressed in this report are those of the authors and do not necessarily reflect those of the HTA Programme, the NIHR, the NHS, or the Department of Health. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates; however, the opinions expressed in this publication are those of the authors, and might not be shared by the Chief Scientist Office.",

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T1 - Medical expulsive therapy in adults with ureteric colic

T2 - a multicentre, randomised, placebo-controlled trial

AU - Pickard, Robert

AU - Starr, Kathryn

AU - MacLennan, Graeme

AU - Lam, Thomas Boon Leong

AU - Thomas, Ruth

AU - Burr, Jennifer

AU - McPherson, Gladys

AU - McDonald, Alison

AU - Anson, Kenneth

AU - N'Dow, James

AU - Burgess, Neil

AU - Clark, Terry

AU - Kilonzo, Mary

AU - Gillies, Kate

AU - Shearer, Kirsty

AU - Boachie, Charles

AU - Cameron, Sarah

AU - Norrie, John

AU - McClinton, Samuel

N1 - Acknowledgments Special thanks must go to all of the SUSPEND trial participants and staff at each of our recruiting centres for taking part in this trial. We thank our collaborators at the SUSPEND sites, and participating National Health Service (NHS) trusts and boards (NHS Grampian, Plymouth Hospitals NHS Trust, The Newcastle upon Tyne Hospitals NHS Foundation Trust, NHS Highland, South Tees Hospitals NHS Foundation Trust, City Hospitals Sunderland NHS Foundation Trust, The Leeds Teaching Hospitals NHS Trust, North Bristol NHS Trust, University Hospitals Bristol NHS Trust, Norfolk and Norwich University Hospitals NHS Foundation Trust, The Royal Liverpool and Broadgreen University Hospitals NHS Trust, NHS Lothian, Guy's and St Thomas' NHS Foundation Trust, St George's Healthcare NHS Trust, Abertawe Bro Morgannwg University Health Board, Mid Yorkshire Hospitals NHS Trust, South Devon Healthcare NHS Foundation Trust, Sheffield Teaching Hospitals NHS Foundation Trust, Cambridge University Hospitals NHS Foundation Trust, Gloucestershire Hospitals NHS Foundation Trust, University Hospitals Birmingham NHS Foundation Trust, Central Manchester University Hospitals NHS Foundation Trust, Southampton University Hospitals NHS Trust, and The University Hospital of South Manchester NHS Foundation Trust). We thank the staff at the SUSPEND trial office based in the Centre for Healthcare Randomised Trials (CHaRT) within the Health Services Research Unit, University of Aberdeen. This report presents independent research funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme, Project Number 08/71/01. The views and opinions expressed in this report are those of the authors and do not necessarily reflect those of the HTA Programme, the NIHR, the NHS, or the Department of Health. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates; however, the opinions expressed in this publication are those of the authors, and might not be shared by the Chief Scientist Office.

PY - 2015/7/25

Y1 - 2015/7/25

N2 - BackgroundMeta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting.MethodsFor this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18–65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 μg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238.FindingsBetween Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI −5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [–5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain).InterpretationTamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic.FundingUK National Institute for Health Research Health Technology Assessment Programme.

AB - BackgroundMeta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting.MethodsFor this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18–65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 μg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238.FindingsBetween Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI −5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [–5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain).InterpretationTamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic.FundingUK National Institute for Health Research Health Technology Assessment Programme.

U2 - 10.1016/S0140-6736(15)60933-3

DO - 10.1016/S0140-6736(15)60933-3

M3 - Article

SN - 0140-6736

VL - 386

SP - 341

EP - 349

JO - The Lancet

JF - The Lancet

IS - 9991

ER -

Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial

Abstract

Bibliographical note

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Kate Gillies

Mary Kilonzo

Thomas Lam

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