Evaluating the Efficacy of a Multistrain Probiotic Supplementation for Prevention of Neonatal Sepsis in 0-2 Months Old Low Birth Weight Infants in India – The ‘ProSPoNS’ Study Protocol for a Phase III, Multicentric, Randomized, Double-Blind, Placebo-Controlled Trial.

Abstract

Abstract Background: Progress has been made in reduction of under five mortality in India, however, neonatal mortality is reducing at a slower rate. Efforts are required to bring down neonatal mortality in order to attain the SDG-3. Prevention of sepsis among the high risk, vulnerable low birth weight neonates by a newer intervention with probiotic supplementation is promising.Methods/design: A phase III, multicentre, randomized, double blind, placebo-controlled is being conducted at six sites in India. A total of 6144 Healthy LBW infants fulfilling the eligibility criteria would be enrolled within first week of life, after obtaining written informed consent from the parents of the infant. Randomization in 1:1 ratio, stratified by site, sex and birth weight would be done through an interactive web response system (IWRS) using a standard web browser and email service Vivomixx R a probiotic containing a mix of 8 strains of bacteria, in a suspension form standardized to deliver 10 billion CFU/ml, or an organoleptically similar placebo would be fed to enrolled infants in a 1ml/day dose for 30 days. The follow-up of enrolled infants would take place as per a pre-specified schedule for recording morbidities and outcome assessments at the six participating sites. Screening for morbidities would be conducted by trained field workers in the community, and sick infants would be referred to designated clinics/hospitals. A physician would examine the referred infants presenting with complaints and clinical signs, blood samples would be collected from sick infants for diagnosis of neonatal sepsis by performingsepsis screen and blood culture. Appropriate treatment would be provided as per hospital protocol. Study would be implemented as per the MRC guideline for management of Global Health Trials in accordance with ICH-GCP and Indian Regulatory guidelines. A Contract Research Organization would be enaged for comprehensive monitoring and quality assurance. . The final analysis would be conducted in a blinded manner as per the statistical analysis plan (SAP) to estimate the primary outcomes sepsis, possible serious Bacterial Infection (PSBI) & secondary outcomes. The codes will be broken after DMEC permission. The protocol has been reviewed by the Research Ethics Committee of the Liverpool School of Tropical Medicine (REC-LSTM), from Research Ethics Committees of the six subject recruitment participating sitesDiscussion: This adequately powered and well-designed trial would conclusively answer the question whether probiotics can prevent neonatal sepsis in the high risk group of Low Birth Weight infants as indicated by a pilot study in 1340 LBW infants, evidence from systematic reviews of hospital based studies and a primary study on healthy newborns in Orissa. Results of the study would be generalizable to India and other Low–middle income countries.Trial registration: The study is registered at the Clinical Trial Registry of India (CTRI; 1 http://ctri.nic.in); Number CTRI/2019/05/019197, date 16 May 2019).