|- candidate number||5633|
|- NTR Number||NTR1769|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||20-apr-2009|
|- Secondary IDs||2005-005745-18 EudraCT|
|- Public Title||Levamisole treatment for children with steroid sensitive nephrotic syndrome.|
|- Scientific Title||Levamisole treatment for children with steroid sensitive nephrotic syndrome. A multicentre, double-blind, placebo-controlled, randomised trial.|
|- ACRONYM||Levamisole trial|
|- hypothesis||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
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
4. To determine whether the effectiveness of Levamisole remains constant or wanes
5. To assess the pharmacokinetics of Levamisole in the target population;
6. To assess the safety of treatment with Levamisole.
|- Healt Condition(s) or Problem(s) studied||Nephrotic syndrome, Idiopathic|
|- Inclusion criteria||1. Primary diagnosis: frequently relapsing idiopathic Steroid Sensitive Nephrotic Syndrome with or without steroid dependency;|
2. 2 > Age < 18 years;
3. Written informed consent.
|- Exclusion criteria||1. Patients previously treated with Levamisole;|
2. Patients unresponsive to Cyclosporine or MMF;
3. Nephrotic syndrome due to a specific kidney disease (such as Henoch –Schoenlein purpura, acute infectious glomerulonefritis, Lupus erythematosus or associated with Hepatitis B or C…);
4. Patients presenting with neutropenia, convulsions or with hepatic diseases;
5. Patients with a prolongation of the QTc-time on the surface electrocardiogram;
6. Pregnancy, breast-feeding or planned pregnancy during the study;
7. Participation in another trial.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||23-mei-2007|
|- planned closingdate||23-nov-2013|
|- Target number of participants||100|
|- Interventions||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.
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
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).
|- Primary outcome||The primary endpoint is defined as the time to relapse which is the time between start of the study medication and occurrence of a relapse or, in case of no relapse, time of censoring (12 months after start of trial medication). Only a relapse necessitating prednisone treatment is considered a primary endpoint relapse.
Proposed end of the blinded part of the study is in all patients 12 months after start of the study medication.|
|- Secondary outcome||1. Average quantity in milligrams of steroids administered per month during the study;|
2. Evaluation whether treatment effect differs with underlying disease process (steroid dependency yes/no) and prior use of disease modifying agents (yes/no);
3. Maintenance dose prednisone at time of relapse.
|- Timepoints||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.
|- Trial web site||www.levamisoletrial.com|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES|| M. Gruppen|
|- CONTACT for SCIENTIFIC QUERIES||Dr. J.C. Davin|
|- Sponsor/Initiator ||Academic Medical Center (AMC), Amsterdam|
(Source(s) of Monetary or Material Support)
|Dutch Kidney Foundation (Nierstichting Nederland), Academic Medical Center (AMC), Emma Children's Hospital, Europese Unie (EU), Dutch Orphan Disease Foundation, French ministry of health, ACE Pharmaceuticals |
|- Publications||Davin JC, Merkus MP. -
Levamisole in steroid-sensitive nephrotic syndrome of childhood: the
Pediatr Nephrol. 2005 Jan;20(1):10-4.
|- Brief summary||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. |
|- Main changes (audit trail)|
|- RECORD||20-apr-2009 - 23-sep-2009|