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NCT Number: NCT04235816

Improving Care Through Azithromycin Research for Infants in Africa

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.

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Key information

Conditions

Child Mortality Infections Malaria Mosquito-Borne Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Age range

6 week–8 week

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

College of Medicine and Allied Health Sciences

Freetown, Sierra Leone

About this study

In order to generate the conclusive evidence needed to inform policy and accelerate the implementation of this intervention, we propose to carry out a large-scale clinical trial on the impact on all-cause mortality up to 18 months of age of AZi administration through EPI. The potential development of antibiotic and SP resistance, AZi and SP interactions with routine immunizations, as well as the safety and the impact on the health system will be all assessed in the ICARIA trial.

To provide the evidence needed to inform policy and practice and to accelerate the implementation of this intervention, a large-scale clinical trial on the impact on all-cause mortality up to 18 months of age of AZi administration through the World Health Organisation Expanded Program on Immunisation (EPI) will be carried out in Sierra Leone. The clinical trial will be individually randomised, placebo-controlled with a factorial design whereby AZi will be administered alongside routine preventive health interventions of the EPI, such as immunisations and Intermittent Preventive Treatment in infants (IPTi), which is recommended by the WHO for malaria prevention in this age group. The potential development of antibiotic resistance, the interactions with routine immunisations, the safety and the impact on the health system of AZi administration will be all assessed in this trial.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

Azithromycin

Drug

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

Other names: AZi, Sumamed

Placebo

Drug

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

Primary outcomes

  1. The rate of all-cause mortality

    Time frame: 18 months of age

    all-cause mortality rate at 18 months of age

Secondary outcomes

  1. The cause-specific mortality rate

    Time frame: 18 months of age

    Cause-specific mortality rate at 18 months of age

  2. Malaria related mortality

    Time frame: 18 month of age

    Malaria related mortality at 18 months of age

  3. Incidence of all-cause hospital admissions

    Time frame: Through study completion, 36 months

    Incidence of all-cause hospital admissions

  4. Incidence of all-cause outpatient attendances

    Time frame: Through study completion, 36 months

    Incidence of all-cause outpatient attendances at the health facilities

  5. Incidence of confirmed (RDT positive) malaria hospital admissions

    Time frame: Through study completion, 36 months

    Incidence of confirmed (RDT positive) malaria hospital admissions at all health facilities

  6. Incidence of confirmed (blood smear positive/RDT positive) malaria hospital admissions

    Time frame: Through study completion, 36 months

    Incidence of confirmed (blood smear positive/RDT positive) malaria hospital admissions at all health facilities

  7. Frequency and severity of drug adverse reactions

    Time frame: Through study completion, 36 months

    Frequency and severity of drug adverse reactions throughout the trial

  8. Prevalence of macrolide resistance in nasopharyngeal isolates

    Time frame: Through study completion, 36 months

    Prevalence of macrolide resistance in nasopharyngeal isolates

  9. Prevalence of macrolide resistance in the gut bacteria

    Time frame: Through study completion, 36 months

    Prevalence of macrolide resistance in the gut bacteria

  10. Proportion of children with protective antibody responses to specific routine EPI immunizations (measles and yellow fever)

    Time frame: Through study completion, 36 months

    Proportion of children with protective antibody responses to specific routine EPI

Sponsors and collaborators

Lead sponsor

Barcelona Institute for Global Health

Other

Collaborators

  • Bill and Melinda Gates Foundation
  • La Caixa Foundation
  • Ministry of Health and Sanitation, Sierra Leone
  • University of Sierra Leone

Registry information

Official study title

Evaluation of the Impact on Childhood Mortality of Azithromycin Plus Intermittent Preventive Treatment Administered Through the Expanded Program on Immunization in Sierra Leone

Acronym: ICARIA

Important dates

Study start
2021
Primary completion
2025
Study completion
2026
First posted
Jan 22, 2020
Registry last updated
Mar 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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