Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation

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Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome : phase III randomised controlled trial and economic evaluation. / PREDNOS Collaborative Group.

In: BMJ, Vol. 365, l1800, 23.05.2019.

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@article{bdca26f9f31348b1b5f304903cac9707,
title = "Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome: phase III randomised controlled trial and economic evaluation",
abstract = "Objective To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. Design Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. Setting 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. Participants 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. Interventions Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m 2) or a standard eight week course of prednisolone (total dose 2240 mg/m 2). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more). Main outcome measures The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. Results No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval-0.005 to 0.037) and cost savings (difference-£1673 ($2160; €1930), 95% confidence interval-£3455 to £109). Conclusions Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. Trial registration ISRCTN16645249; EudraCT 2010-022489-29.",
keywords = "Adolescent, Child, Child, Preschool, Cost-Benefit Analysis, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Drug Monitoring/methods, Female, Glucocorticoids/administration & dosage, Humans, Immunosuppressive Agents/therapeutic use, Infant, Intention to Treat Analysis, Long-Term Care/economics, Male, Nephrotic Syndrome/diagnosis, Prednisolone/administration & dosage, Quality of Life, Secondary Prevention/economics, Treatment Outcome",
author = "{PREDNOS Collaborative Group} and Webb, {Nicholas J. A.} and Rebecca Woolley and Tosin Lambe and Emma Frew and Elizabeth Brettell and Emma Barsoum and Trompeter, {Richard S.} and Carole Cummins and Jonathan Deeks and Keith Wheatley and Natalie Ives",
note = "Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.",
year = "2019",
month = may,
day = "23",
doi = "10.1136/bmj.l1800",
language = "English",
volume = "365",
journal = "BMJ",
issn = "0959-8138",
publisher = "BMJ Publishing Group",

}

RIS

TY - JOUR

T1 - Long term tapering versus standard prednisolone treatment for first episode of childhood nephrotic syndrome

T2 - phase III randomised controlled trial and economic evaluation

AU - PREDNOS Collaborative Group

AU - Webb, Nicholas J. A.

AU - Woolley, Rebecca

AU - Lambe, Tosin

AU - Frew, Emma

AU - Brettell, Elizabeth

AU - Barsoum, Emma

AU - Trompeter, Richard S.

AU - Cummins, Carole

AU - Deeks, Jonathan

AU - Wheatley, Keith

AU - Ives, Natalie

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PY - 2019/5/23

Y1 - 2019/5/23

N2 - Objective To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. Design Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. Setting 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. Participants 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. Interventions Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m 2) or a standard eight week course of prednisolone (total dose 2240 mg/m 2). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more). Main outcome measures The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. Results No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval-0.005 to 0.037) and cost savings (difference-£1673 ($2160; €1930), 95% confidence interval-£3455 to £109). Conclusions Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. Trial registration ISRCTN16645249; EudraCT 2010-022489-29.

AB - Objective To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. Design Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. Setting 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. Participants 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. Interventions Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m 2) or a standard eight week course of prednisolone (total dose 2240 mg/m 2). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more). Main outcome measures The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. Results No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval-0.005 to 0.037) and cost savings (difference-£1673 ($2160; €1930), 95% confidence interval-£3455 to £109). Conclusions Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. Trial registration ISRCTN16645249; EudraCT 2010-022489-29.

KW - Adolescent

KW - Child

KW - Child, Preschool

KW - Cost-Benefit Analysis

KW - Dose-Response Relationship, Drug

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Drug Monitoring/methods

KW - Female

KW - Glucocorticoids/administration & dosage

KW - Humans

KW - Immunosuppressive Agents/therapeutic use

KW - Infant

KW - Intention to Treat Analysis

KW - Long-Term Care/economics

KW - Male

KW - Nephrotic Syndrome/diagnosis

KW - Prednisolone/administration & dosage

KW - Quality of Life

KW - Secondary Prevention/economics

KW - Treatment Outcome

UR - http://www.scopus.com/inward/record.url?scp=85066009544&partnerID=8YFLogxK

U2 - 10.1136/bmj.l1800

DO - 10.1136/bmj.l1800

M3 - Article

C2 - 31335316

AN - SCOPUS:85066009544

VL - 365

JO - BMJ

JF - BMJ

SN - 0959-8138

M1 - l1800

ER -