Safety and immunogenicity of live attenuated vaccines during corticosteroid therapy in children with nephrotic syndrome: An open-label, non-inferiority design, randomized controlled trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- To compare the proportion of participants achieving seroconversion to either varicella or MMR vaccine or both, 4 weeks after administration, between two groups of children with nephrotic syndrome (administered during the last 2 weeks of alternate day corticosteroid therapy versus administered 4 weeks after discontinuation of steroids).
研究概览
简要总结
Existing knowledge gaps: Nephrotic syndrome is treated with daily high dose corticosteroid therapy, followed by low-moderate dose corticosteroid therapy (lmCT - 1.5 mg/kg alternate day; 40 mg maximum dose). Indian guidelines mention to avoid live attenuated vaccines (LAV; measles, mumps, rubella [MMR] and/or varicella zoster vaccine [VZV]) till end of lmCT. However, most clinicians wait for 4 weeks after completion of therapy, leading to a missed opportunity for vaccination in this vulnerable cohort.
Novelty: This study will generate prospective data, on the immunogenicity and safety of LAV in NS in children at the end of low-moderate dose corticosteroid therapy, compared against the standard of care vaccination practice.
Objectives: Comparison of seroconversion to LAV at 4 weeks, in children with nephrotic syndrome, during the last 2 weeks of lmCT versus those administered LAV after 4 weeks of stopping lmCT.
Methods: Children >=1 year of age with NS, who present to the outpatient and inpatient departments, in remission of NS with lmCT, will undergo screening for seroprotection against varicella, mumps, measles and rubella. Immune response (humoral and cell-mediated) will be assessed in this population and randomized into early and standard interventions groups if found eligible. Early intervention group will receive LAV during the last 2 weeks of lmCT while standard intervention group will receive LAV 4 weeks after completion of lmCT, after obtaining written informed consent. Siblings of recruited children, or healthy children with no history of measles, mumps, rubella or varicella, and no detectable antibodies against any of these viruses, will be enrolled as healthy controls. Redosing of vaccine will be done to prevent waning of responses, at 12 weeks after first dose, (in remission of NS). Vaccine response titers will be assessed in all participants at 4, prior to 2nd dose, 8 weeks after 2nd dose and at 52 weeks, with all patients followed for 1 year. Adverse events occurring during the study period will be monitored and assessed by the Data Safety Monitoring Board. Prospective registration will be performed at Clinical Trials Registry of India and the Institutional Review Board.
Expected outcome: Safety and immunogenicity of LAV during lmCT (last 2 weeks of alternate day corticosteroid therapy) in children with NS can be established, which can be incorporated into Indian guidelines.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 1.00 Year(s) 至 18.00 Year(s)（—）
- 性别
- All
入选标准
- •Age at screening more than 12 months
- •Currently on therapy with steroids for NS.
- •Proteinuria in remission with urine protein creatinine ratio less than 0.2 mg/mg 4 .Ongoing prednisolone therapy with less than 1.5 mg/kg (maximum 40 mg) alternate day dose.
- •Normal immune responsiveness satisfying both a) b) and c) at baseline a. Humoral immunity with IgG level more than 300 mg/dL b. Cellular immunity with CD4+ T cells more than 500/mm3, c. Cellular immunity functional assay.
- •normal lymphocyte blast transformation by phytohemagglutinin (stimulation index more than 101.6) If any criteria is negative, repetition can be done after 1 week to reassess for enrolment (especially time to IgG recovery can be slower after relapse). If two assays performed 1 week apart show any defect in immune responses, patient will be re-rescreened after 4 weeks if in remission.
- •Negative seroprotective titers for any one of mumps, measles, rubella and varicella (MMR/V) (negative values below 11, 16.5,10 and 150 AU per ml for mumps, measles, rubella and varicella, respectively).
- •Written informed consent from parents/legally accepted representatives.
排除标准
- •1.Suspected or proven sepsis currently or within 1 week of enrollment 2.Estimated glomerular filtration rate less than or equal to 90 ml/min per 1.73 m2 (as per modified Schwartz equation) 3.History of anaphylaxis/allergy to varicella or MMR vaccines, or its components 4.Currently on therapy with levamisole, mycophenolate mofetil, tacrolimus, rituximab (on or up to 6 months after last dose) or cyclophosphamide (on or up to 3 months after last dose) or steroids more than 1.5 mg/kg (maximum 40 mg) alternate day dose
- •Patients living more than 200 km from the center and unwilling for follow-up as planned 6.Leucopenia, neutropenia or lymphopenia (total WBC less than or equal to 4,000/mm3, absolute neutrophil and lymphocyte count less than or equal to 1,500/mm3)
- •Blood or blood products or immunoglobulin received in the last 12 months.
- •Secondary nephrotic syndrome (lupus, IgA nephropathy, membranous or membranoproliferative glomerulonephritis, etc.)
- •Children who had varicella, mumps, measles or rubella illness in the last 8 weeks (clinical or virological diagnosis)
- •Children who are currently in contact with a pregnant woman at their home.
结局指标
主要结局
To compare the proportion of participants achieving seroconversion to either varicella or MMR vaccine or both, 4 weeks after administration, between two groups of children with nephrotic syndrome (administered during the last 2 weeks of alternate day corticosteroid therapy versus administered 4 weeks after discontinuation of steroids).
时间窗: 4 weeks after administration of intervention
次要结局
- • Mean geometric mean titers for antibodies against the 4 viruses will be compared across the two groups(4 weeks after administration of intervention)
- Safety of LAV in NS, as measured by SAEs(1 year of followup)
研究者
Dr Georgie Mathew
Christian Medical College, Vellore