Description

This is a 5-arm randomized, unblinded clinical trial comparing:

Arm 1: Standard-of-care (control) Arm 2: Antimicrobial package Arm 3: Reformulated RUTF Arm 4: Psychosocial package Arm 5: Antimicrobial package + reformulated RUTF + psychosocial package

The trial will test the superiority of each intervention arm over the standard of care arm (control). Children in the control arm (and all intervention arms) will receive RUTF for at least 2 weeks and all standard care. The trial is adaptive, meaning i) that each intervention arm will be added as it becomes available, and ii) an interim analysis will enable us to drop arms which are unpromising based on pre-specified criteria. There will be no blinding or placebo, because the very different components in each trial arm make it very challenging to blind. Children with complicated SAM will be screened and enrolled from hospital sites shortly before discharge, and interventions will be started before leaving hospital, and continued for 12 weeks through outpatient visits. Children will be followed at 2, 4, 6, 8, 12 and 24 weeks post-discharge in dedicated study clinics (with additional visits at 1, 3 and 5 weeks for caregiver-child pairs receiving the psychosocial intervention).

The primary outcome is death or hospitalization or failed nutritional recovery by 24 weeks.

The aim is to recruit 1266 children across three countries. The study is not testing new drugs but rather testing a different package of medications (Arms 2 and 5) as compared to current standard care, which the investigator believe will have greater benefit. The RUTF will be a new formula in two of the arms (3 and 5) based on research into what composition will improve health outcomes for children with complicated SAM. This will be a variant on Plumpy'Nut®, a brand that is known and trusted, produced in collaboration with the manufacturers, Nutriset.

The Psychosocial intervention (Arms 4 and 5) will involve three components:

i) The Friendship Bench, which was developed in Zimbabwe as a low-cost psychological intervention utilising problem-solving therapy (delivered by trained lay workers) and peer-to-peer support to address depression and other common mental disorders. There is a strong evidence-base for its use in urban LMIC settings. Peer support groups meet every 1-2 weeks and focus on communal problem solving, and establishing income-generation activities (such as making bags). ii) Care for Child Development is a UNICEF package that helps families build stronger relationships and solve problems in caring for the child at home, through play and communication activities to stimulate children, through a series of age-appropriate interactive modules delivered by a lay worker using 'flash' cards. It has been used in other African contexts and has good acceptability. iii) Educational and behavior-change messages around better nutrition; play for children with SAM; stigma, HIV and gender-based violence; financial planning; causes of SAM; and health-seeking behaviours.

Blood and stool will be collected at baseline, 12 and 24 weeks from all children to explore recovery of underlying pathological processes. At week 2, liver function tests will be undertaken in local laboratories. Samples will also be transported to Kenya and the Netherlands for some assays not available in each country.