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

Queen Mary University of London

Status and phase: Active, not recruiting; Phase 3

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

Treatments: Behavioral: The Friendship Bench; Drug: Pyridoxine Hydrochloride; Drug: Isoniazid; Behavioral: Other Behavioural Support; Behavioral: Care for Child Development; Drug: Rifampicin; Drug: Azithromycin; Other: Standard Care

Study type: Interventional

Funder types: Other

Identifiers

NCT05994742

150522

Details and patient eligibility

About

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.

Full 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.

Enrollment: 674 patients

Sex: All

Ages: 6 to 59 months old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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674 participants in 3 patient groups

Arm 1: Standard-of-care (control)

Active Comparator group

Description:

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.

Treatment:

Other: Standard Care

Arm 2: Antimicrobial package

Experimental group

Description:

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

Treatment:

Other: Standard Care

Drug: Azithromycin

Drug: Rifampicin

Drug: Isoniazid

Drug: Pyridoxine Hydrochloride

Arm 3: Psychosocial Support (PSS) Package

Experimental group

Description:

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).

Treatment:

Other: Standard Care

Behavioral: Care for Child Development

Behavioral: Other Behavioural Support

Behavioral: The Friendship Bench