Efficiency of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children
Condition: First Manifestation of Steroid Sensitive Nephrotic Syndrome
MeSH terms: Nephrotic Syndrome; Nephrosis; Hypersensitivity; Syndrome
Study type: Interventional
Phase: Phase 3

Summary: 
      Idiopathic Nephrotic Syndrome is sensitive to steroid in 90% of children. However, most
      patients relapse and become steroid-dependant, with a long lasting relapsing course. The aim
      of this study is to assess the efficiency of a 6-months levamisole course, given early after
      first remission, on maintaining a relapse-free course at 12 months.
    

Detailed description: 
      Introduction (INS) is likely a primal immune disorder. Initial treatment relies on steroid
      therapy. NS is sensitive to steroid in more than 90% of cases, with an excellent renal
      prognosis. Nevertheless, 80% of patients with steroid sensitive NS do relapse, 60% within the
      first year. 2/3 of them will experience steroid dependency, with a long lasting relapsing
      course. These patients require further immunosuppressive drugs as steroid sparing agents,
      such as mycophenolate, cyclophosphamide, calcineurin inhibitors or rituximab. Morbidity is
      high and related both to the duration of the disease, sometimes until adulthood, and to
      treatments side effects.

      Levamisole is an immunomodulator that has been used for more than thirty years in the
      treatment of steroid-dependent or frequently relapsing NS. Its major advantages are its
      immunomodulatory action and lower and reversible toxicity.

      Exact physiopathology of both INS and levamisole action remain unknown. Nevertheless, we make
      the hypothesis that very early treatment with levamisole may enhance its efficiency and
      modify the disease's course.

      This is the first trial to assess the efficiency of levamisole in increasing duration of
      remission after the first manifestation of INS.

      Design :

        -  A multicenter, double-blind, placebo-controlled, randomised clinical trial.

        -  38 centers participate to the recruitment : 3 Pediatric Nephrology units and 35 General
           Pediatric units.

        -  20 centers participate to the randomized phase.

      Sample size :

      156 patients, 78 in each group

      Treatment groups :

        1. Levamisole Hydrochloride Dosage : 5, 10, 25 et 50mg. Dosage form : oral tablets Posology
           : 2.5 mg/kg on alternate days maximum 150mg. Treatment duration : 6 months

        2. placebo : matching verum

      Assessment :

      Study visits at inclusion, M1 (randomisation), M3, M6, M9, M12. Supplementary visit if
      relapse occurs.

      Statistical procedure Analysis of efficiency will be performed on intention to treat
      population. Analysis of tolerance will be performed on randomized patients who have received
      at least one dose of treatment.

      No intermediary analysis is planned.
    

Intervention name(s): Levamisole Hydrochloride; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Dosage : 5, 10, 25 et 50 mg. Dosage form : oral tablets, coated and non dividable for taste-masking Posology : 2.5 mg/kg on alternate days maximum 150mg. Treatment duration : 6 months; matching verum
Intervention MeSH terms: Levamisole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Idiopathic nephrotic syndrome; Steroid sensitive nephrotic syndrome; Levamisole; Prednisone; Children