Short course daily prednisolone therapy at the time of upper respiratory tract infection in children with relapsing steroid sensitive nephrotic syndrome: the PREDNOS 2 study

• Register: ISRCTN
• Last refreshed on: 7 February 2022
• Main ID: ISRCTN10900733
• Date of registration: 26/10/2012
• Prospective Registration: Yes
• Primary sponsor: University of Birmingham (UK)
• Public title: Short course daily prednisolone therapy at the time of upper respiratory tract infection in children with relapsing steroid sensitive nephrotic syndrome: the PREDNOS 2 study
• Scientific title: Short course daily prednisolone therapy at the time of upper respiratory tract infection in children with relapsing steroid sensitive nephrotic syndrome: the PREDNOS 2 study
• Date of first enrolment: 01/11/2012
• Target sample size: 300
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN10900733
• Study type: Interventional
• Study design: Double blind randomised controlled trial (Treatment)
• Phase: Phase III

Countries of recruitment

England, United Kingdom

Contacts

• Name: Adam Khan

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects aged over 1 year and less than 19 years will be eligible for inclusion if they have relapsing SSNS, defined as having experienced 2 or more relapses in the preceding 12 months. This will include the following groups:
1. Subjects on no longterm immunosuppressive therapy
2. Subjects receiving long term maintenance prednisolone therapy at a dose of up to and including 15mg/m2 on alternate days. Note that this is the maximum dose at the time of recruitment. If children subsequently receive a higher dose e.g. after relapse, they can remain in the study.
3. Subjects receiving long term maintenance prednisolone therapy at a dose of up to and including 15mg/m2 on alternate days in conjunction with other immunosuppressive therapies, including levamisole, ciclosporin, tacrolimus, MMF, mycophenolate sodium and azathioprine
4. Subjects receiving longterm immunosuppressive therapies, including levamisole, ciclosporin, tacrolimus, MMF, mycophenolate sodium and azathioprine without long term maintenance prednisolone therapy.
5. Subjects who have previously received a course of oral or intravenous cyclophosphamide:
5.1. Must have experienced two relapses in the 12 months prior to randomisation (in keeping with all other subjects)
5.2. Must have experienced at least one of these relapses following completion of cyclophosphamide therapy
5.3. Must be at least 3 months post completion of oral or intravenous cyclophosphamide therapy
6. Subjects who have previously received a single dose or course of intravenous rituximab:
6.1. Must have experienced two relapses in the 12 months prior to randomisation (in keeping with all other subjects)
6.2. Must have experienced at least one of these relapses following completion of rituximab therapy
6.3. Must be at least 3 months post completion of intravenous rituximab therapy
7. Parents and (where age appropriate) subject understand the definition of URTI and the need to commence study drug once this definition has been met
8. Written informed consent obtained from the subject?s parents/guardians and written assent obtained from subject (where age appropriate). Subjects aged 16 years and above will provide their own written informed consent.

Exclusion criteria:
1. Subjects with steroid resistant nephrotic syndrome
2. Subjects receiving, or within 3 months of completing a course of oral or intravenous cyclophosphamide
3. Subjects receiving, or within 3 months of receiving a course of rituximab
4. Subjects on daily prednisolone therapy at time of recruitment
5. Subjects on a long term maintenance prednisolone dose of greater than 15mg/m2 on alternate days at time of recruitment
6. Subjects with a documented history of significant nonadherence with medical therapy
7. Subjects who will be transferred from paediatric to adult services during the 12 month study period
8. Subjects unable to take prednisolone tablets, even in crushed form
9. Known allergy to prednisolone


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Steroid sensitive nephrotic syndrome
Urological and Genital Diseases
Nephrotic syndrome

Intervention(s)

Randomised to receive either 6 days of daily prednisolone or continue unchanged on their existing therapy (the current standard of care) each time they develop a URTI over a 12 month period.

Primary Outcome(s)

Current primary outcome measure as of 17/10/2019:
First URTI-related relapse of nephrotic syndrome during the 12-month follow-up period.

Relapse is defined as Albustix positive proteinuria (+++ or greater) for three consecutive days or the presence of generalised oedema plus 3+ proteinuria. URTI-related relapse is defined as a relapse occurring within 14 days of the development of an URTI. First URTI-related relapse refers to the first URTI-related relapse which occurs within the 12-month study follow-up period.

Previous primary outcome measure:
URTI-related relapse of nephrotic syndrome following first URTI during 12 month follow-up period. Relapse is defined as Albustix positive proteinuria (+++ or greater) for 3 consecutive days or the presence of generalised oedema plus 3+ proteinuria. URTI-related relapse is defined as a relapse occurring within 14 days of the development of an URTI. First URTI refers to the first URTI which occurs within the 12 month study follow up period. Relapse will be assessed at each clinic visit which will be every three months for a period of one year in keeping with routine clinical practice.

Secondary Outcome(s)

1. Rate of URTI-related relapse of nephrotic syndrome (relapses per year)
2. Rate of relapse (URTI-related and non URTI-related) of nephrotic syndrome (relapses per year)
3. Cumulative dose of prednisolone (mg/kg and mg/m2) received over the 12 month study period
4. Incidence of SAEs
5. Incidence of adverse effects of prednisolone including assessment of behaviour using the Achenbach Child Behaviour Checklist
6. Incidence of escalation of background immunosuppressive therapy (e.g. addition of ciclosporin, tacrolimus, cyclophosphamide etc.)
7. Incidence of reduction of background immunosuppressive therapy (i.e. cessation of long term maintenance prednisolone therapy)
8. Quality of life using the CHU-9D, EQ-5D and PedsQL
9. Cost per relapse of nephrotic syndrome
10. Cost per QALY gained

Secondary ID(s)

13410

2012-003476-39

Source(s) of Monetary Support

Health Technology Assessment Programme 11/129/261

Ethics review

Status:
Approval date:
Contact:

North West GM Central Research Ethics Committee (REC), Ref. No: 12/NW/0766 - approval pending

Results

• Results available: Yes
• Date Completed: 31/07/2020