REduceren van STEroiden bij kinderen met een Recidief Nefrotisch syndroom – de RESTERN studie

Most children with steroid sensitive nephrotic syndrome experience several relapses, which are treated with steroids. For most children, long-term prognosis is for complete resolution of their disease over time and maintenance of normal kidney function. It is therefore vital to focus on minimizing adverse events of the disease and its therapy. Unfortunately, no randomized controlled trials are available to determine the optimal steroid treatment of an infrequent relapse of the nephrotic syndrome.

Recent studies show that treatment schedules of the first episode can safely be reduced (Hahn et al., 2015; Hoyer, 2015), which may reduce steroid toxicity. The hypothesis of the REducing STEroids in Relapsing Nephrotic syndrome (RESTERN) study is that a 2-4-week reduction of alternate day steroids after inducing remission is effective and safe, reduces steroid exposure by 35% on average, and is therefore preferable.

Using a nation-wide placebo-controlled randomized controlled trial, this hypothesis will be tested. A similar daily dose of prednisone is used until the induction of remission. Randomization in blocks (immunosuppressive maintenance therapy vs. no maintenance therapy) will be performed for either 4-6 weeks of alternate day prednisone (standard therapy) or 2 weeks alternate day prednisone followed by 2-4 weeks of alternate day placebo. For a non-inferiority trial with 80% power, 72 patients per group are needed, for which an estimated inclusion rate of 53% is needed.

The RESTERN project aims to improve clinical care for children with nephrotic syndrome by showing that at least equal clinical benefits can be obtained by reduced corticosteroid exposure, which minimizes toxicity.

The main hypothesis is that relapses of the nephrotic syndrome in children can be treated adequately by a reduced duration of alternate day prednisone (2 weeks instead of the currently used 4-6 weeks) after a similar induction of remission.

12 months

24 months

Treatment schedule

• Prednisone 60mg/m2 (max 60mg) daily in 1 dose until complete remission for 3 days (according to the KDIGO guideline)

• Randomization:

o Standard treatment: 4-6 weeks prednisone 40mg/m2 (max 40mg) every other day, then stop (no tapering)

o Study treatment: 2 weeks prednisone 40mg/m2 (max 40mg) every other day, then 2-4 weeks placebo every other day, then stop (no tapering)

Treatment of subsequent relapses according to Dutch standards (prednisone 60mg/m2 (max 60mg) daily in 1 dose until complete remission for 3 days, continued with prednisone 40mg/m2 (max 40mg) every other day during 6 weeks)