NCT05994742

An Adaptive Multi-arm Trial to Improve Clinical Outcomes Among Children Recovering From Complicated SAM

Co-SAM: An Adaptive Multi-arm Trial to Improve Clinical Outcomes Among Children Recovering From Complicated Severe Acute Malnutrition

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 674 (actual)
• Sponsor: Queen Mary University of London · Academic / Other
• Sex: All
• Age: 6 Months – 59 Months
• Healthy volunteers: Not accepted

Summary

Malnutrition underlies 45% of child deaths, and has far-reaching educational, economic and health consequences. Severe acute malnutrition (SAM) affects 17 million children globally and is the most life-threatening form of malnutrition. Community-based management of acute malnutrition using ready-to-use therapeutic food (RUTF) has transformed outcomes for children with uncomplicated SAM, but those presenting with poor appetite or medical complications (categorised as having 'complicated' SAM) require hospitalisation. Data show that pneumonia, diarrhoea and malaria are leading causes of death in children with complicated SAM after discharge from hospital. High risk of infectious deaths suggests that sustained antimicrobial interventions may reduce mortality following discharge from hospital. Furthermore, children with complicated SAM respond less well to nutritional rehabilitation, and oftentimes are discharged to a home environment characterised by poverty and multiple caregiver vulnerabilities including depression, low decision making autonomy, lack of social support, gender-restricted family relations, and competing demands on scarce resources. Caregivers have to navigate diverse challenges that impede engagement with clinical care after discharge from hospital. The objective is to address the biological and social determinants of multimorbidity in children with complicated SAM by comparing an antimicrobial intervention with standard of care.

Detailed description

This is a 3-arm randomized, unblinded clinical trial comparing: Arm 1: Standard-of-care (control) Arm 2: Antimicrobial package Arm 3: 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 study is not testing new drugs but rather testing a different package of medications as compared to current standard care, which are designed to prevent a range of infections during convalescence. The Psychosocial intervention 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.

Conditions

• Severe Acute Malnutrition
• HIV
• Comorbidities and Coexisting Conditions
• Child Malnutrition

Interventions

Type	Name	Description
DRUG	Rifampicin	Rifampicin is commonly used in the first-line management of paediatric tuberculosis, and is approved by the FDA (ID: 2862628) and the EMA (EMA/31710/2020).
DRUG	Azithromycin	Azithromycin is a macrolide antibiotic, and is approved for use in children by the FDA (ID: 3263750) and EMA (EMA/2872/2021).
DRUG	Isoniazid	Isoniazid is an antibiotic commonly used in the firstline treatment of tuberculosis, and as tuberculosis prophylaxis.
DRUG	Pyridoxine Hydrochloride	Pyridoxine is a form of vitamin B6 used to prevent peripheral neuropathy among children receiving isoniazid.
OTHER	Standard Care	All children will receive care according to WHO guidelines, which includes standard RUTF and any other medications required.
BEHAVIORAL	The Friendship Bench	The Friendship Bench 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).
BEHAVIORAL	Care for Child Development	Care for Child Development is a UNICEF package that helps families build stronger relationships and solve problems in caring for their 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.
BEHAVIORAL	Other Behavioural Support	Educational and behaviour-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. These have been developed with caregivers affected by SAM in a previous study, through a series of co-design workshops, ensuring they are contextually relevant.

Timeline

• Start date: 2024-07-15
• Primary completion: 2026-08-15
• Completion: 2026-08-15
• First posted: 2023-08-16
• Last updated: 2026-03-19

Locations

9 sites across 3 countries: Kenya, Zambia, Zimbabwe