Safety and immunogenicity of live attenuated vaccines during corticosteroid therapy in children with nephrotic syndrome: protocol for an open-label, non-inferiority, randomised controlled trial (VACCINES trial: VAccines in Children on CorticosteroIds

INTRODUCTION: Live attenuated vaccines (LAVs) are recommended during moderate corticosteroid therapy (<2 mg/kg per day) for nephrotic syndrome (NS) largely based on observational/case-control study data. We aim to conduct a randomised controlled trial (RCT) to assess the safety and immunogenicity of LAVs in children with NS. METHODS AND ANALYSIS: To test the safety and immunogenicity of LAVs in NS in children on moderate dose corticosteroid therapy (1.5 mg/kg alternate day dose with maximum 40 mg alternate day dose; early arm) vs those off corticosteroid therapy for 4 weeks (standard arm), we are conducting a single-centre, open-label, non-inferiority RCT at a tertiary care centre in South India (VACCINES trial: Vaccines in Children on Corticosteroids for NEphrotic Syndrome). Eligible children (after inclusion and exclusion criteria) will be enrolled after obtaining written informed consent (from a legally accepted representative/parents) as well as assent for children aged >12 years. Two doses of measles, mumps, rubella (MMR) and/or varicella vaccines will be administered 12 weeks apart, after the initial assessment of seroprotection. Immunological assessment of humoral and cellular immunity will be evaluated in eligible participants. Randomisation into the standard and early arms will be performed during the last 2 weeks of alternate-day therapy (stratified into first episode and relapse patients). Seroconversion assessments will be made at 4, 12, 16 and 52 weeks into the study. The primary objective is to compare the proportion of participants who demonstrate seroconversion after 4 weeks of the first intervention. The secondary outcomes are the antibody geometric mean titres and adverse event profiles including serious events. With a non-inferiority margin of 15% (assuming 86% seroconversion in healthy controls), power of 85% and an alpha error of 5%, 100 patients (including 10% attrition) will be randomised (1:1). Comparisons with 50 healthy children will also be made. The occurrence of three serious adverse events directly attributable to the intervention constitutes a stopping rule. An interim analysis after recruitment of 50% is planned to be presented to an institutional Data Safety Monitoring Board. The first patient was enrolled on 30 June 2025, and enrolment is expected to be completed by February 2028. ETHICS AND DISSEMINATION: The trial has been approved by the Institutional Review Board (IRB) of the Christian Medical College, Vellore (IRB min 2411130, dated 20 November 2024). Results will be published in a peer-reviewed journal and may be presented at medical conferences. TRIAL REGISTRATION NUMBER: Clinical Trials Registry - India, CTRI/2025/01/078854 (Jan 16, 2025).