Improving Care Through Azithromycin Research for Infants in Africa

NCT04235816 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: ICARIAOPP1196642
• Study Type: interventional
• Target: 20,560
• Locations: 1 country
• Sites: 1

Brief Summary

Infectious diseases are among the most common causes of mortality in the over 2.5 million children under 5 years of age (U5) who died in 2018 in sub-Saharan Africa (SSA). New approaches to treatment and prevention of these diseases are needed to increase child survival. Sierra Leone has one of the highest rates of under-five child mortality in the world. It is estimated that 32,000 children die each year, the leading causes being neonatal conditions, malaria, pneumonia and diarrhea. In Sierra Leone, the available information on malaria indicates that it accounts for 38% of deaths among under-five children. Reducing the prevalence and impact of the disease among the general population is a major priority of the Ministry of Health and Sanitation (MoHS) of Sierra Leone . Intermittent Preventative Treatment in infants (IPTi) - the administration of a full course antimalarial treatment to infants at individual timepoints regardless of infection status- has been shown to reduce clinical malaria and anemia in infants in the first year of life . When delivered alongside the Expanded Program on Immunization (EPI), IPTi with Sulphadoxine-pyrimethamine (SP) is a highly cost-effective intervention. . Sierra Leone is currently the only country that implements nationwide the World Health Organization's (WHO) IPTi guideline, which is administered within the first year of life. However, its benefit when expanded into the second year of life remains unknown. Taking the advantage of the inclusion in the EPI program of a booster dose of measles vaccine at 15 months of age, the ICARIA trial will also assess the efficacy of adding a dose of IPTi-SP at this age. Recent studies show that azithromycin (AZi) - a macrolide antibiotic with some antimalarial effect- is associated with a significant reduction in childhood mortality when used in mass drug administration (MDA) for trachoma elimination in areas of sub-Saharan Africa (SSA) with child mortality rates far beyond Sustainable Development Goals , . However, despite the potential benefit of the intervention several fundamental scientific questions need to be answered before it can be recommended for large-scale implementation.

Conditions

Child Mortality

Keywords

Infant; U5; Azithromycin; Intermittent preventive treatment for infants; Expanded Program on Immunization; Malaria; Sulphadoxine-pyrimethamine

Outcome Measures

Primary Outcomes (1)

• The rate of all-cause mortality

  all-cause mortality rate at 18 months of age

  18 months of age

Secondary Outcomes (10)

• The cause-specific mortality rate

  18 months of age

• Malaria related mortality

  18 month of age

• Incidence of all-cause hospital admissions

  Through study completion, 36 months

• Incidence of all-cause outpatient attendances

  Through study completion, 36 months

• Incidence of confirmed (RDT positive) malaria hospital admissions

  Through study completion, 36 months

Study Arms (2)

Group 1

ACTIVE COMPARATOR

AZi at DTP-1 visit at 6 weeks of age, AZi (plus IPTi) at measles visit at 9 months of age and AZi (plus IPTi) at measles booster visit at 15 months of age.

Drug: Azithromycin

Group 2

PLACEBO COMPARATOR

Placebo at DTP-1 visit at 6 weeks of age, placebo (plus IPTi) at measles visit at 9 months of age and placebo (plus IPTi) at measles booster visit at 15 months of age.

Drug: Placebo

Interventions

Azithromycin DRUG

Administration of azithromycin during the first 15 months of life through the Expanded Program on Immunisation

Also known as: AZi, Sumamed

Group 1

Placebo DRUG

Administration of placebo during the first 15 months of life through the Expanded Program on Immunisation

Group 2

Eligibility Criteria

• Age: 6 Weeks - 8 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Parents/guardians have signed the informed consent
• Permanent residence in the study area-health facility catchment area
• Without known allergies to or contraindications to macrolides
• Without known allergies to or contraindications to SP
• Agreement to complete the EPI scheme at the recruitment health facility
• Parents/guardians agree to participate

You may not qualify if:

• Residence outside the study area or planning to move out in the following 12 months from enrolment
• Known history of allergy or contraindications to macrolides and/or SP
• Known history of allergy or contraindications to SP
• With signs of any acute illness at the time of recruitment
• Participating in other intervention studies

Sponsors & Collaborators

• Ministry of Health and Sanitation, Sierra Leone: collaborator
• Bill and Melinda Gates Foundation: collaborator
• La Caixa Foundation: collaborator
• Barcelona Institute for Global Health: lead
• University of Sierra Leone: collaborator

Study Sites (1)

College of Medicine and Allied Health Sciences

Freetown, Sierra Leone

Location

Related Publications (2)

• Chen H, Owusu-Kyei K, Fombah AE, Williams J, Garcia-Fernandez C, Rovira-Vallbona E, Bofill A, Quinto L, Figueroa-Romero A, Mac-Abdul F, Samai M, Mayor A, Menendez C. Prevalence of Molecular Markers of Resistance to Antimalarial Drugs Three Years After Perennial Malaria Chemoprevention in Sierra Leone. Gates Open Res. 2025 Oct 8;9:81. doi: 10.12688/gatesopenres.16367.1. eCollection 2025.

  PMID: 41080970 DERIVED

• Owusu-Kyei K, Chen H, Chileshe M, Quinto L, Sibley M, Figueroa-Romero A, Llach M, Ramirez M, Bofill A, Samai M, Menendez C; ICARIA Trial Team. Impact of oral azithromycin and intermittent preventive treatment with sulfadoxine-pyrimethamine regimen on child mortality in Sierra Leone: trial protocol for a randomised, two-arm, double-blinded, placebo-controlled clinical trial (ICARIA). Trials. 2024 Sep 27;25(1):626. doi: 10.1186/s13063-024-08443-9.

  PMID: 39334260 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Clara Menendez, MD, PhD

  Barcelona Institute for Global Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple: (Participant, Care Provider, Investigator, Outcomes Assessor)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2-arm individually randomized placebo-controlled clinical trial of AZi administration in young children from Sierra Leone.

Study Record Dates

• First Submitted: January 17, 2020
• First Posted: January 22, 2020
• Study Start: March 15, 2021
• Primary Completion: September 11, 2025
• Study Completion: April 30, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

SI (1)