Prednisolone in nephrotic syndrome

ISRCTN	ISRCTN16645249
DOI	https://doi.org/10.1186/ISRCTN16645249
EudraCT/CTIS number	2010-022489-29
Secondary identifying numbers	9617

Submission date: 17/02/2011
Registration date: 17/02/2011
Last edited: 25/07/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Urological and Genital Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Background and study aims
Nephrotic syndrome is a chronic disorder that occurs during childhood where the kidneys do not work properly, causing large amounts of protein to leak into the urine. This loss of protein can cause swelling of body tissues and increase the chance of catching infections. Initial treatment is with steroid drugs. This is usually successful but patients can relapse and require more treatment. The best duration of initial steroid treatment remains uncertain. We aim to compare two months versus four months of steroid (prednisolone) treatment. Both of these durations have been used in clinical practice, but we are unsure which is best. Previous research has suggested that with longer treatment, fewer children relapse, but the quality of the research was not very good and the results may be biased. We would like to carry out a further, better quality, study.

Who can participate?
Children aged 1 - 15 with nephrotic syndrome

What does the study involve?
The children are randomly allocated to either two months or four months of prednisolone treatment. All the children take tablets for the same amount of time, but the children in the shorter treatment group take dummy (placebo) tablets in the last weeks. The main outcome we are interested in is how many children relapse and need further treatment for nephrotic syndrome. The children are asked to test their urine with dipsticks as the presence of protein in the urine is a sign of relapse. We also investigate how many children relapse frequently and how many are unable to manage without taking steroids and how relapses are treated. We look at how long it is before patients relapse. Although prednisolone is an effective drug in the treatment of nephrotic syndrome it does have side effects. These include making patients more vulnerable to infection, changes in facial appearance, hairiness, increased appetite, weight gain and a tendency to more aggressive behaviour. We do not know how often these side effects occur in the treatment of nephrotic syndrome from previous research, nor do we know what the impact of them is on parents and children and how important they are to families. We wish to find out whether there are more side effects with longer treatment. As part of this, we ask parents to complete a questionnaire about their child's behaviour at the beginning and at the peak of treatment, as well as checking regularly for side effects. As well as looking at how well the treatments work, we look at which is best value for the NHS. We follow the children up until the end of the study and each child is followed for at least 12 months.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Birmingham Clinical Trials Unit (UK)

When is the study starting and how long is it expected to run for?
February 2011 to May 2015

Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK)

Who is the main contact?
Elizabeth Brettell
E.a.brettell@brum.ac.uk

Study website

Contact information

Mrs Elizabeth Brettell
Scientific

Birmingham Clinical Trials Unit
Division of Cancer Studies
Robert Aitken Institute
Edgbaston
Birmingham
B15 2TT
United Kingdom

Email	E.a.brettell@brum.ac.uk

Study information

Study design	Multicentre randomised interventional treatment trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Can be found at http://www.bctu.bham.ac.uk/prednos/investigators/Documents.shtml
Scientific title	Long-term tapering versus standard prednisolone (steroid) therapy for the treatment of the initial episode of childhood nephrotic syndrome: national multicentre randomised double-blind trial
Study acronym	PREDNOS
Study hypothesis	PREDNOS is a national multicentre randomised double blind trial of long-term tapering versus standard prednisolone (steroid) therapy for the treatment of the initial episode of childhood nephrotic syndrome. Further details can be found at: http://www.nets.nihr.ac.uk/projects/hta/085331 Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0008/52982/PRO-08-53-31.pdf
Ethics approval(s)	NRES Committee North West, 05/04/2011, ref: 10/H1008/122
Condition	Topic: Medicines for Children Research Network; Subtopic: All Diagnoses; Disease: All Diseases
Intervention	Standard course therapy: Weeks 1 - 4: prednisolone 60 mg/m2/day (max 80 mg) Weeks 5 - 8: prednisolone 40 mg/m2 (max 60 mg) Duration: given on alternate days for 28 days Extended course therapy: Weeks 1 - 4: prednisolone 60 mg/m2/day (max 80 mg) Weeks 5 - 16: prednisolone 60 mg/m2 (max 80 mg) Duration: given on alternate days tapering by 10 mg/m2 every 2 weeks Study entry: single randomisation only
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Prednisolone
Primary outcome measure	Time to first relapse. Relapse of proteinuria is defined by Albustix positive proteinuria (++ or greater) for 3 consecutive days.
Secondary outcome measures	1. Relapse rate 2. Incidence of frequently relapsing steroid sensitive nephrotic syndrome (defined as 2 relapses or more in the first six months following presentation or 4 relapses within any 12 month period) 3. Incidence of steroid dependent nephrotic syndrome (defined as relapses on or within 14 days of completion of steroid therapy) nephrotic syndrome 4. Incidence of use of second line immunosuppressive agents, including levamisole, cyclophosphamide, ciclosporin, tacrolimus, mycophenolate mofetil and rituximab 5. Incidence of serious adverse events 6. Incidence of adverse events 7. Incidence of behavioural change (as assessed by the Achenbach child behaviour checklist) 8. Cost per relapse of proteinuria 9. Cost per QALY gained Assessment schedule: Clinical trial follow-up assessments will be at weeks 4, 8, 12 and 16 and months 5, 6, 8, 10 and 12, 18, 24, 30, 36, 42 and 48. All patients will be followed up for at least 24 months and for a variable time period beyond 24 months until 24 months after the last patient is randomised.
Overall study start date	01/02/2011
Overall study end date	01/05/2015

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	1 Year
Upper age limit	15 Years
Sex	Both
Target number of participants	Planned sample size: 224
Total final enrolment	237
Participant inclusion criteria	Children presenting with the first episode of steroid sensitive NS who meet all of the following criteria: 1. Urine albumin: creatinine ratio greater than 200 mg/mmol or protein: creatinine ratio greater than 200 mg/mmol, determined quantitatively on an early morning urine sample 2. Serum/plasma albumin level less than 25 g/L 3. Age over 1 year and less than 15 years at the time of diagnosis (children of 15 years and above have been excluded because of the reduced likelihood of their nephrotic syndrome being steroid sensitive and the increased likelihood of adult causes of nephrotic syndrome) 4. No prior therapy with steroids, immunosuppressive or cytotoxic agents for any form of renal disease (other than the 28 days of prednisolone therapy given initially as routine clinical practice) 5. No evidence of underlying systemic disorder or exposure to agents known to be associated with newly presenting steroid sensitive nephrotic syndrome 6. Informed consent
Participant exclusion criteria	1. Children with histological changes other than minimal lesion glomerulonephritis where renal biopsy has been undertaken 2. Children with a prior history of poor compliance with medical therapy 3. Known allergy to prednisolone
Recruitment start date	01/02/2011
Recruitment end date	01/05/2015

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Birmingham Clinical Trials Unit

Birmingham
B15 2TT
United Kingdom

Sponsor information

University of Birmingham (UK)
University/education

c/o Dr Brendan W Laverty
Assistant Director
Research & Commercial Services
Birmingham Research Park
University of Birmingham
Edgbaston
Birmingham
B15 2SQ
England
United Kingdom

Website	http://www.rcs.bham.ac.uk

Central Manchester University Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

c/o Dr Lynne Webster
Research and Innovation Division
1st Floor, Postgraduate Centre
Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
England
United Kingdom

Email	lynne.webster@cmft.nhs.uk
Website	www.cmft.nhs.uk

University of Birmingham
Not defined

Website	http://www.birmingham.ac.uk/index.aspx
"ROR"	https://ror.org/03angcq70

Funders

Funder type

Government

Health Technology Assessment Programme
Government organisation / National government

Alternative name(s): NIHR Health Technology Assessment Programme, HTA
Location: United Kingdom

Results and Publications

Intention to publish date	31/12/2018
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results			21/05/2019	No	No
Results article	HTA results	01/05/2019	04/06/2019	Yes	No
Results article	results	23/05/2019	25/07/2019	Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

25/07/2019: Publication reference added.
04/06/2019: Publication reference added.
21/05/2019: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
01/06/2018: The intention to publish date has been changed from 01/09/2017 to 31/12/2018.
31/05/2018: No publications found, verifying study status with principal investigator.
15/04/2016: Plain English summary added.