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

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.

Conditions

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

Interventions

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.

Sponsors & Collaborators

• University of Oxford

  collaborator OTHER

• KEMRI-Wellcome Trust Collaborative Research Program

  collaborator OTHER

• University of Washington

  collaborator OTHER

• Wageningen University

  collaborator OTHER

• Zvitambo Institute for Maternal & Child Health

  collaborator UNKNOWN

• Tropical Gastroenterology & Nutrition Group (TROPGAN)

  collaborator OTHER

• University of Cambridge

  collaborator OTHER

• Kenya Medical Research Institute

  collaborator OTHER

• National Institute for Health Research, United Kingdom

  collaborator OTHER_GOV

• Queen Mary University of London

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

6 Months

Max Age

59 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-07-15

Primary Completion

2026-08-15

Completion

2026-08-15

Countries

• Kenya
• Zambia
• Zimbabwe

Study Locations