First Manifestation of Steroid Sensitive Nephrotic Syndrome
Conditions
Keywords
Idiopathic nephrotic syndrome, Steroid sensitive nephrotic syndrome, Levamisole, Prednisone, Children
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.
Interventions
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
OTHERPlacebo
matching verum
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
24 Months to 16 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
France
Outcome results
None listed