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

NCT05994742 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: 150522
• Study Type: interventional
• Target: 674
• Locations: 3 countries
• Sites: 9

Brief 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

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

Outcome Measures

Primary Outcomes (1)

• Death or first hospitalisation or failed nutritional recovery within 24 weeks post-randomisation

  a) All-cause mortality. b) Overnight admission to a health facility for any reason. This includes cases where there was a clinical plan to hospitalise the child, which was refused by the caregiver. c) Failed nutritional recovery is defined as either: i) Persistent WHZ\<-2 or MUAC\<12.5cm or bilateral pedal oedema at week 12; or ii) WHZ\<-2 or MUAC\<12.5cm or bilateral pedal oedema at any time between baseline and week 24 post-randomisation in a child who had previously recovered.

  24 weeks post-randomisation

Secondary Outcomes (5)

• Change in weight-for-height Z-score

  24 weeks post-randomisation

• Change in mid-upper arm circumference

  24 weeks post-randomisation

• Change in weight-for-age Z-score

  24 weeks post-randomisation

• Change in height-for-age Z-score

  24 weeks post-randomisation

• Number of participants with suspected or confirmed tuberculosis,pneumonia, diarrhoea or malaria

  24 weeks post-randomisation

Other Outcomes (8)

• Change in anthropometry: Weight-for-height Z score (WHZ)

  4 weeks post-randomisation and 12 weeks post-randomisation

• Change in anthropometry: Weight-for-age Z score (WAZ)

  4 weeks post-randomisation and 12 weeks post-randomisation

• Change in anthropometry: Height-for-age Z score (HAZ)

  4 weeks post-randomisation and 12 weeks post-randomisation

Study Arms (3)

Arm 1: Standard-of-care (control)

ACTIVE COMPARATOR

Children in the control arm will receive Ready to Use Therapeutic Food (RUTF) for at least 2 weeks, plus all standard care. Children with HIV will receive long-term Cotrimoxazole prophylaxis and antiretroviral therapy, as per current guidelines.

Other: Standard Care

Arm 2: Antimicrobial package

EXPERIMENTAL

Children will receive a bundle of azithromycin (3 days every month), isoniazid (daily), rifampicin (daily) and pyridoxine (daily) for 12 weeks.

Drug: Rifampicin; Drug: Azithromycin; Drug: Isoniazid; Drug: Pyridoxine Hydrochloride; Other: Standard Care

Arm 3: Psychosocial Support (PSS) Package

EXPERIMENTAL

During the Psychosocial Support intervention, caregiver-child pairs receive weekly intervention visits at weeks 1, 3, and 5. These visits are designed to deliver weekly problem-solving therapy and behavior-change modules for a total duration of 6 weeks. The content and focus of these psychosocial sessions aim to support the psychosocial well-being of the participants. Additionally, there are standard intervention visits for all arms at weeks 2, 4, 6, 8, and 12 post-randomization, which include other aspects of the intervention such as the resupply of Ready-to-Use Therapeutic Food (RUTF).

Other: Standard Care; Behavioral: The Friendship Bench; Behavioral: Care for Child Development; Behavioral: Other Behavioural Support

Interventions

Azithromycin DRUG

Azithromycin is a macrolide antibiotic, and is approved for use in children by the FDA (ID: 3263750) and EMA (EMA/2872/2021).

Arm 2: Antimicrobial package

Rifampicin DRUG

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).

Arm 2: Antimicrobial package

Isoniazid DRUG

Isoniazid is an antibiotic commonly used in the firstline treatment of tuberculosis, and as tuberculosis prophylaxis.

Arm 2: Antimicrobial package

Pyridoxine Hydrochloride DRUG

Pyridoxine is a form of vitamin B6 used to prevent peripheral neuropathy among children receiving isoniazid.

Arm 2: Antimicrobial package

Standard Care OTHER

All children will receive care according to WHO guidelines, which includes standard RUTF and any other medications required.

Arm 1: Standard-of-care (control); Arm 2: Antimicrobial package; Arm 3: Psychosocial Support (PSS) Package

The Friendship Bench BEHAVIORAL

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).

Arm 3: Psychosocial Support (PSS) Package

Care for Child Development BEHAVIORAL

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.

Arm 3: Psychosocial Support (PSS) Package

Other Behavioural Support BEHAVIORAL

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.

Arm 3: Psychosocial Support (PSS) Package

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6-59 months, of either sex
• Hospitalised with complicated severe acute malnutrition, as per WHO definition
• Started transition to RUTF
• Caregiver willing and able to attend the study clinic for all visits
• Caregiver able and willing to give informed consent

You may not qualify if:

• Any acute or chronic condition which mean that receipt of one or more study interventions, or participation in the trial, would not be advisable.

Sponsors & Collaborators

• Queen Mary University of London: lead
• University of Oxford: collaborator
• KEMRI-Wellcome Trust Collaborative Research Program: collaborator
• University of Washington: collaborator
• Wageningen University: collaborator
• Zvitambo Institute for Maternal & Child Health: collaborator
• Tropical Gastroenterology & Nutrition Group (TROPGAN): collaborator
• University of Cambridge: collaborator
• Kenya Medical Research Institute: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (9)

Homa Bay

Homa Bay, Kenya

Location

Mbagathi Hospital

Mbagathi, Kenya

Location

Migori Referral Hospital

Migori, Kenya

Location

Coast General

Mombasa, Kenya

Location

Matero Hospital

Lusaka, Zambia

Location

UTH - University Teaching Hospital

Lusaka, Zambia

Location

Chitungwiza Central Hospital

Harare, Zimbabwe

Location

Parirenyatwa Hospital

Harare, Zimbabwe

Location

Sally Mugabe Hospital

Harare, Zimbabwe

Location

Related Publications (1)

• Bwakura-Dangarembizi M, Amadi B, Singa BO, Muyemayema S, Ngosa D, Mwalekwa L, Ngao N, Kazhila L, Mutasa B, Mpofu E, Mudawarima L, Gonzales GB, Mudzingwa S, Mutenda M, Keter LK, Mutasa K, Njunge JM, Jones H, Phiri TN, Mudibo E, Chulu N, Majo FD, Chasekwa B, Tembo A, Nyabinda C, Oduol C, Sauramba V, Tavengwa NV, Langhaug L, Cordani I, Smuk M, Jaki T, Ntozini R, Walson J, Tickell KD, Berkley J, Kelly P, Prendergast AJ; Co-SAM Trial Team. An adaptive multiarm randomised trial of biomedical and psychosocial interventions to improve convalescence following severe acute malnutrition in sub-Saharan Africa: Co-SAM trial protocol. BMJ Open. 2025 May 24;15(5):e093758. doi: 10.1136/bmjopen-2024-093758.

  PMID: 40413053 DERIVED

MeSH Terms

Conditions

Severe Acute Malnutrition; Child Nutrition Disorders

Interventions

Rifampin; Azithromycin; Isoniazid; Pyridoxine; Standard of Care; Child Development

Condition Hierarchy (Ancestors)

Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Hydrazines; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring; Vitamin B 6; Picolines; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Human Development; Growth and Development; Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Adaptive, multi-arm randomised controlled trial

Study Record Dates

• First Submitted: July 14, 2023
• First Posted: August 16, 2023
• Study Start: July 15, 2024
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): August 15, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: January 2028
• Access Criteria: Via ClinEpiDB

Locations

ZA (2); ZI (3); KE (4)