Background and study aims
Steroid sensitive nephrotic syndrome (SSNS) is the commonest kidney disease of childhood. Large amounts of protein are leaked into the urine resulting in generalised oedema (swelling). Treatment is with high dose oral prednisolone, a steroid drug which is effective, though associated with a number of serious side effects. Following successful initial treatment, 70-80% of children develop relapses where leakage of protein into the urine recurs. These are associated with a risk of significant complications. Treatment of relapse of nephrotic syndrome is with a further course of high dose prednisolone, further increasing the risk of side-effects. Children are kept off school, resulting in educational impairment and parental absence from work. Around 50% of children suffer frequent relapses (4 or more per year). In this situation, attempts are made to reduce prednisolone exposure using other more potent drugs e.g. ciclosporin and cyclophosphamide, which are associated with other significant side-effects. It is therefore logical to attempt to reduce the frequency of relapses.
There is known to be a strong link between viral upper respiratory tract infection (URTI the common cold) and the development of relapse of nephrotic syndrome. Three previous small studies have suggested that the use of a short course of daily prednisolone at the time of URTI reduces the rate of disease relapse. The PREDNOS 2 study aims to determine whether the use of such therapy effectively and safely reduces the rate of relapse in a large population of UK children.
Who can participate and what does the study involve?
Participants aged over 1 year and less than 19 years will be eligible for inclusion in the PREDNOS 2 study if they have relapsing SSNS, defined as having experienced 2 or more relapses in the preceding 12 months. We will randomise 300 children with relapsing SSNS 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. We will assess the incidence of URTI-related relapse of nephrotic syndrome in both study arms and look carefully for side-effects of treatment. The 300 participants will be recruited from over 120 UK hospitals.
What are the possible benefits and risks of participating?
Participants will receive a six day course of prednisolone each and every time they develop an URTI over the 12 month study period. The aim of this is to try and prevent the development of URTI-related relapse, necessitating the commencement of high dose daily prednisolone therapy. There is the risk that this course of action will increase overall steroid exposure without reducing relapse rate. We will be monitoring patients every three months and will carefully document steroid-related adverse events, including impact on behaviour. Those children who experience steroid toxicity during the course of the study will have their background immunosuppressive therapy enhanced in an attempt to reduce relapse frequency. There will be no additional study visits for the purposes of the study alone. The three monthly visits are in keeping with routine care in children with relapsing nephrotic syndrome.
When is the study starting and how long is it expected to run for?
PREDNOS 2 opened to recruitment 22nd February 2013 and was originally expected to recruit for a 2 year period however recruitment into the study is now open until at least March 2016. Each subject will be followed-up every 3 months over a period of 1 year which is in keeping with routine clinical practice. The trial has been funded for a total of 4 years allowing for 6 months set up, 2 years recruitment, 1 year follow-up and 6 months data analysis and report writing.
Study set-up and contract details
The PREDNOS 2 Chief Investigator is Professor Nicholas Webb who is based at Royal Manchester Children’s Hospital (Nicholas.Webb@cmft.nhs.uk). The PREDNOS 2 trial is being co-ordinated by the Birmingham Clinical Trials Unit (PREDNOS2@trials.bham.ac.uk) and further information can be found on the trial website: www.birmingham.ac.uk/prednos2. PREDNOS 2 has been funded by the National Institute for Health Research Health Technology Assessment programme (NIHR HTA Ref: 11/129/261). PREDNOS 2 is co-sponsored by the University of Birmingham and Central Manchester University Hospitals NHS Foundation Trust. PREDNOS 2 has been approved by the North West GM Central Research Ethics Committee (REC), Ref. No: 12/NW/0766 and also has the following reference numbers: EudraCT Number: 2012-003476-39 and ISRCTN10900733.