Efficiency of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children

Phase 3

Completed

• Conditions: First Manifestation of Steroid Sensitive Nephrotic Syndrome
• Interventions: Drug: Levamisole Hydrochloride; Other: Placebo

• Registration Number: NCT02818738
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study First Submitted: 2016-06-08
• Study First Submitted QC: 2016-06-27
• Study First Posted: 2016-06-30
• Study Start: 2017-09-06
• Primary Completion: 2021-02-07
• Study Completion: 2021-02-11
• Status Verified: 2022-05
• Last Update Submitted: 2022-06-07
• Last Update Posted: 2022-06-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 86

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Levamisole Hydrochloride	Levamisole Hydrochloride	Dosage : 5, 10, 25 et 50mg. 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
Placebo	Placebo	matching verum

Primary Outcome Measures

Name	Time	Method
Percentage of patients still in remission at 12 months after first flare of INS.	12 months	number of patients who did not relapse compared to the number of patients who had relapsed after first flare of INS.

Secondary Outcome Measures

Name	Time	Method
Compare within levamisole and placebo groups the duration of remission.	first relapse	number of days between the first flare and first relapse or up to the corticodependence level in the event of relapse in the course of decreasing corticosteroid therapy.
Compare within levamisole and placebo groups the frequency and level of steroid dependency	12 months	Proportion of corticodependent patients and level of steroid dependency
Compare within levamisole and placebo groups the treatment tolerance	12 months	Frequency of adverse events apparition and frequency of discontinuation of treatment secondary at a adverse event.

Trial Locations

Locations (1)

Hôpital Robert Debré; 🇫🇷 Paris, France