Efficiency of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children (NEPHROVIR3)
Primary Purpose
First Manifestation of Steroid Sensitive Nephrotic Syndrome
Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Levamisole Hydrochloride
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for First Manifestation of Steroid Sensitive Nephrotic Syndrome focused on measuring Idiopathic nephrotic syndrome, Steroid sensitive nephrotic syndrome, Levamisole, Prednisone, Children
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)
Sites / Locations
- Hôpital Robert Debré
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Levamisole Hydrochloride
Placebo
Arm Description
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
matching verum
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Compare within levamisole and placebo groups the frequency and level of steroid dependency
Proportion of corticodependent patients and level of steroid dependency
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.
Full Information
NCT ID
NCT02818738
First Posted
June 8, 2016
Last Updated
June 7, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT02818738
Brief Title
Efficiency of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children
Acronym
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.
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
September 6, 2017 (Actual)
Primary Completion Date
February 7, 2021 (Actual)
Study Completion Date
February 11, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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 :
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
First Manifestation of Steroid Sensitive Nephrotic Syndrome
Keywords
Idiopathic nephrotic syndrome, Steroid sensitive nephrotic syndrome, Levamisole, Prednisone, Children
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
86 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Levamisole Hydrochloride
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
matching verum
Intervention Type
Drug
Intervention Name(s)
Levamisole Hydrochloride
Intervention Description
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
Other
Intervention Name(s)
Placebo
Intervention Description
matching verum
Primary Outcome Measure Information:
Title
Percentage of patients still in remission at 12 months after first flare of INS.
Description
number of patients who did not relapse compared to the number of patients who had relapsed after first flare of INS.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Compare within levamisole and placebo groups the duration of remission.
Description
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.
Time Frame
first relapse
Title
Compare within levamisole and placebo groups the frequency and level of steroid dependency
Description
Proportion of corticodependent patients and level of steroid dependency
Time Frame
12 months
Title
Compare within levamisole and placebo groups the treatment tolerance
Description
Frequency of adverse events apparition and frequency of discontinuation of treatment secondary at a adverse event.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
24 Months
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claire DOSSIER, MD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Robert Debré
City
Paris
ZIP/Postal Code
75019
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficiency of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children
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