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

First Manifestation of Steroid Sensitive Nephrotic Syndrome Clinical Trial

— NEPHROVIR3  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02818738
• Other study ID #: P150904
• Status: Completed
• Phase: Phase 3
• Start date: September 6, 2017
• Est. completion date: February 11, 2021

Study information

• Verified date: May 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: February 11, 2021
• Est. primary completion date: February 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 24 Months to 16 Years

Eligibility

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)

Related Conditions & MeSH terms

• First Manifestation of Steroid Sensitive Nephrotic Syndrome
• Hypersensitivity
• Nephrosis
• Nephrotic Syndrome
• Syndrome

Intervention

Drug:
• 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

Other:
• Placebo
matching verum

Locations

Country	Name	City	State
France	Hôpital Robert Debré	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients still in remission at 12 months after first flare of INS.	number of patients who did not relapse compared to the number of patients who had relapsed after first flare of INS.	12 months
Secondary	Compare within levamisole and placebo groups the duration of remission.	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.	first relapse
Secondary	Compare within levamisole and placebo groups the frequency and level of steroid dependency	Proportion of corticodependent patients and level of steroid dependency	12 months
Secondary	Compare within levamisole and placebo groups the treatment tolerance	Frequency of adverse events apparition and frequency of discontinuation of treatment secondary at a adverse event.	12 months