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

NCT ID: NCT02818738

Last Updated: 2022-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-06
• Study Completion Date: 2021-02-11

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.

Conditions

First Manifestation of Steroid Sensitive Nephrotic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

Levamisole Hydrochloride

Intervention Type: DRUG

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

Placebo

matching verum

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

matching verum

Interventions

Levamisole Hydrochloride

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

Intervention Type: DRUG

Placebo

matching verum

Intervention Type: OTHER

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)

• Minimum Eligible Age: 24 Months
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Claire DOSSIER, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Robert Debré

Paris, , France

Countries

France

References

Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.

Reference Type: DERIVED

PMID: 39513526 (View on PubMed)

Other Identifiers

P150904

Identifier Type: -

Identifier Source: org_study_id