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Efficiency of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children (NEPHROVIR3)

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ClinicalTrials.gov Identifier: NCT02818738
Recruitment Status : Recruiting
First Posted : June 30, 2016
Last Update Posted : July 18, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
First Manifestation of Steroid Sensitive Nephrotic Syndrome Drug: Levamisole Hydrochloride Other: Placebo Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 156 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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.
Actual Study Start Date : September 6, 2017
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy

Arm Intervention/treatment
Experimental: 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
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

Placebo Comparator: Placebo
matching verum
Other: Placebo
matching verum




Primary Outcome Measures :
  1. Percentage of patients still in remission at 12 months after first flare of INS. [ Time Frame: 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 :
  1. Compare within levamisole and placebo groups the duration of remission. [ Time Frame: 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.

  2. Compare within levamisole and placebo groups the frequency and level of steroid dependency [ Time Frame: 12 months ]
    Proportion of corticodependent patients and level of steroid dependency

  3. Compare within levamisole and placebo groups the treatment tolerance [ Time Frame: 12 months ]
    Frequency of adverse events apparition and frequency of discontinuation of treatment secondary at a adverse event.



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Ages Eligible for Study:   24 Months to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02818738


Contacts
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Contact: Claire DOSSIER, MD 01 40 03 24 67 ext +33 claire.dossier@aphp.fr
Contact: Georges DESCHENES, MD PDH 01 40 03 24 67 ext +33 georges.deschenes@aphp.fr

Locations
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France
Hôpital Robert Debré Recruiting
Paris, France, 75019
Contact: Claire DOSSIER, MD    01 40 03 24 67 ext +33    claire.dossier@aphp.fr   
Contact: Georges DESCHENES, MD PDH    01 40 03 24 67 ext +33    georges.deschenes@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Claire DOSSIER, MD Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02818738     History of Changes
Other Study ID Numbers: P150904
First Posted: June 30, 2016    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Idiopathic nephrotic syndrome
Steroid sensitive nephrotic syndrome
Levamisole
Prednisone
Children

Additional relevant MeSH terms:
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Syndrome
Hypersensitivity
Nephrotic Syndrome
Nephrosis
Disease
Pathologic Processes
Immune System Diseases
Kidney Diseases
Urologic Diseases
Levamisole
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antinematodal Agents
Anthelmintics
Antiparasitic Agents
Anti-Infective Agents
Antirheumatic Agents