Levamisole treatment for children with steroid sensitive nephrotic syndrome.

Annually there are about 100 new children with steroid sensitive nephrotic syndrome in The Netherlands. 50-60% relapse as soon as dosage prednison is stopped or decreased. These children are therefore exposed to toxic side effects of long-term steroids. Among the alternatives used for sparing steroids, levamisole is the least toxic and expensive, however, hardly used. Lack of good quality evidence, no approval for this indication, and difficulty to obtain levamisole may be responsible. An adequately designed RCT is now required to determine whether levamisole is effective in children with SSNS.

This international, multi-centre, double blinded, placebo-controlled, randomised clinical trial will be performed:

To assess the effectiveness of one year of alternate days Levamisole treatment in a dose of 2.5 mg/kg in the prevention of relapses and prolonging time to relapse after cessation of corticosteroids treatment in children with SSNS.

And as secondary analyses:

1. To evaluate whether the effect of Levamisole varies with disease status (steroid dependent vs. frequently relapsing; low vs. high dose steroid dependency);

2. To evaluate whether the effect of Levamisole varies with prior treatment with
Cyclophosphamide;

3. To assess the steroid sparing effect of Levamisole treatment as well as the sparing
effect of other immunosuppressive drugs (i.e. average amount administered per
patient);

4. To determine whether the effectiveness of Levamisole remains constant or wanes
over time;

5. To assess the pharmacokinetics of Levamisole in the target population;

6. To assess the safety of treatment with Levamisole.

1. 05/2007: start inclusion;

2. 05/2011: end inclusion;

3. 05/2012: end cohort, begin wash out;

4. 11/2012: end wash out;

5. 11/2013: final report.

1. Active compound Levamisole Hydrochloride.

Dosage 2,5 mg/kg on alternate days.

Strength 5, 10, 25 and 50 mg.

Dosage form oral tablets, coated and non-dividable for taste-masking.

2. Placebo matching verum.



Study medication:

1. Start: during Prednisone treatment for relapse when patient’s urine is protein free for 3-21 days;

2. Duration: 12 months or until relapse
Concomitant medication.

Cyclosporine, Cyclophosphamide, MMF and other immunosuppressive drugs are not permitted.

Prednisone:given at inclusion during relapse in accordance with the French protocol including tapering (Société de Néphrologie Pédiatrique).

Cohort study: To evaluate whether Levamisole effect remains constant or wanes over time and to evaluate side effects of long term Levamisole treatment, Levamisole patients still in remission at trial
completion will be followed for another 18 months (12 additional months of levamisole plus 6 extra months after Levamisole cessation).