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.