A Phase 3 interventional study of Rifampicin and Azithromycin in Severe Acute Malnutrition, HIV and Comorbidities and Coexisting Conditions, sponsored by Queen Mary University of London. Completed at 9 sites in 3 countries. Open to participants aged 6 Months to 59 Months. Per ClinicalTrials.gov, last updated 2026-08-25.
Sponsored by Queen Mary University of London · Phase 3, Interventional, and Treatment
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.
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.
82 studies on the registry are indexed under Severe Acute Malnutrition; 13 are open to participants now.
This study's enrollment of 674 is above the median of 400 across 69 interventional studies indexed under Severe Acute Malnutrition.
Browse Severe Acute Malnutrition studies →Queen Mary University of London is the lead sponsor of 253 studies on the registry; 58 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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
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).
Azithromycin is a macrolide antibiotic, and is approved for use in children by the FDA (ID: 3263750) and EMA (EMA/2872/2021).
Isoniazid is an antibiotic commonly used in the firstline treatment of tuberculosis, and as tuberculosis prophylaxis.
Pyridoxine is a form of vitamin B6 used to prevent peripheral neuropathy among children receiving isoniazid.
All children will receive care according to WHO guidelines, which includes standard RUTF and any other medications required.
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).
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.
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.
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.
Time frame: 24 weeks post-randomisation
Change in weight-for-height Z-score
Change in weight-for-height Z-score between baseline and 24 weeks post-randomisation according to age- and-sex appropriate WHO reference standards.
Time frame: 24 weeks post-randomisation
Change in mid-upper arm circumference
Change in size of mid-upper arm in centimetres between baseline and 24 weeks.
Time frame: 24 weeks post-randomisation
Change in weight-for-age Z-score
Change in weight-for-age Z-score between baseline and 24 weeks post-randomisation according to age- and sex-appropriate WHO reference standards.
Time frame: 24 weeks post-randomisation
Change in height-for-age Z-score
Change in height-for-age Z-score between baseline and 24 weeks post-randomisation according to age- and sex-appropriate WHO reference standards.
Time frame: 24 weeks post-randomisation
Number of participants with suspected or confirmed tuberculosis,pneumonia, diarrhoea or malaria
Physician-diagnosed suspected or confirmed infection, as defined by WHO guidelines, between baseline and 24 weeks post-randomisation.
Time frame: 24 weeks post-randomisation
Change in anthropometry: Weight-for-height Z score (WHZ)
Change in WHZ between baseline and 4 weeks post-randomisation, and baseline and 12 weeks post-randomisation.
Time frame: 4 weeks post-randomisation and 12 weeks post-randomisation
Change in anthropometry: Weight-for-age Z score (WAZ)
Change in WAZ between baseline and 4 weeks post-randomisation, and baseline and 12 weeks post-randomisation.
Time frame: 4 weeks post-randomisation and 12 weeks post-randomisation
Change in anthropometry: Height-for-age Z score (HAZ)
Change in HAZ between baseline and 4 weeks post-randomisation, and baseline and 12 weeks post-randomisation.
Time frame: 4 weeks post-randomisation and 12 weeks post-randomisation
Change in anthropometry: Mid-upper arm circumference (MUAC)
Change in MUAC between baseline and 12 weeks post-randomisation.
Time frame: 4 weeks post-randomisation and 12 weeks post-randomisation
Change in caregiver mental health
Change in Shona Symptom Questionnaire score (and proportion meeting cut-off score \>8) between baseline and 24 weeks post-randomisation. This is a widely used 10-item self-report questionnaire. Each item is scored from 0-3, leading to a total score between 0-30, with higher scores indicating more severe depressive symptoms.
Time frame: 24 weeks post-randomisation
Concentration of lipid mediators/proteins
LC-MS measurement of fatty acids, acylcarnitines, polyamines, amino acids, glycolysis intermediates, TCA cycle intermediates, nucleotides, prostaglandins, serotonin, bile acids, lysophosphatidylcholines, phosphatidylcholines, cholesterol and derivatives, organic acids and tri/di/monoglycerides.
Time frame: 12 weeks and 24 weeks post-randomisation
Concentration of metabolites
Luminex measurement of Insulin, Insulin-like growth factor 1, leptin, ghrelin, cortisol, growth hormone, Glucagon-like peptide-1, Peptide YY, Monocyte chemoattractant protein-1, and Plasminogen activator inhibitor-1.
Time frame: 12 weeks and 24 weeks post-randomisation
Concentration of inflammatory mediators
Luminex measurement of chemokines, cytokines and circulating growth factors.
Time frame: 12 weeks and 24 weeks post-randomisation
Plan to share: Yes — Data will be shared at the end of the trial on ClinEpiDB.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code
Time frame: January 2028
Access criteria: Via ClinEpiDB
Data sharing details ↗ · clinepidb.org
Ran from Jul 2024 to primary completion in Jul 2026, 24 months.
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Studies of the drugs tested here: Rifampin · Azithromycin · Isoniazid · Pyridoxine
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