Clinical trial NCT02818738: Efficiency of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children
Official title: A Multicenter, Randomised, Double-blind Placebo-controlled Trial Assessing the Efficiency of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: First Manifestation of Steroid Sensitive Nephrotic Syndrome
Keywords: Idiopathic nephrotic syndrome
Steroid sensitive nephrotic syndrome
Levamisole
Prednisone
Children
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2016-06-30
Enrollment: 86
Sex: ALL
Minimum age (years): 24
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Age 24 months \< age \< 16 years
* Diagnosis of first manifestation of INS defined by:
* hypoalbuminemia \< 25g/l, proteinuria \> 0.20 g/mmol of urinary creatinine
* normal C3 fraction of complement
* Use of mechanical contraception for patients of reproductive age throughout the research period
* Beneficiary of a social protection scheme (except AME)
* Written informed consent from one of both parents
* Ability to realise follow-up in full

Exclusion Criteria:

* Anteriority of INS
* Pregnancy, breast feeding or planned pregnancy during the study
* Malignant pathology (antecedent or ongoing), diabetes, liver disease
* Hypersensitivity to levamisole or its excipients (lactose)

Primary outcomes:
measure: Percentage of patients still in remission at 12 months after first flare of INS.
timeFrame: 12 months
Secondary outcomes:
measure: Compare within levamisole and placebo groups the duration of remission.
timeFrame: first relapse
measure: Compare within levamisole and placebo groups the frequency and level of steroid dependency
timeFrame: 12 months
measure: Compare within levamisole and placebo groups the treatment tolerance
timeFrame: 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Robert Debré
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Claire DOSSIER, MD
role: PRINCIPAL_INVESTIGATOR
References: