Improving Care Through Azithromycin Research for Infants in Africa

Child Mortality Clinical Trial

— ICARIA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04235816
• Other study ID #: ICARIA
• Secondary ID: OPP1196642
• Status: Recruiting
• Phase: Phase 3
• Start date: March 15, 2021
• Est. completion date: December 30, 2025

Study information

• Verified date: September 2023
• Source: Barcelona Institute for Global Health
• Contact: Haily Chen, MSc.
• Phone: +34 932275400
• Email: haily.chen[@]isglobal.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20560
• Est. completion date: December 30, 2025
• Est. primary completion date: October 15, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 8 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Child Mortality

Intervention

Drug:
• Azithromycin
Administration of azithromycin during the first 15 months of life through the Expanded Program on Immunisation
• Placebo
Administration of placebo during the first 15 months of life through the Expanded Program on Immunisation

Locations

Country	Name	City	State
Sierra Leone	College of Medicine and Allied Health Sciences	Freetown

Sponsors (5)

Lead Sponsor	Collaborator
Barcelona Institute for Global Health	Bill and Melinda Gates Foundation, La Caixa Foundation, Ministry of Health and Sanitation, Sierra Leone, University of Sierra Leone

Country where clinical trial is conducted

Sierra Leone, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The rate of all-cause mortality	all-cause mortality rate at 18 months of age	18 months of age
Secondary	The cause-specific mortality rate	Cause-specific mortality rate at 18 months of age	18 months of age
Secondary	Malaria related mortality	Malaria related mortality at 18 months of age	18 month of age
Secondary	Incidence of all-cause hospital admissions	Incidence of all-cause hospital admissions	Through study completion, 36 months
Secondary	Incidence of all-cause outpatient attendances	Incidence of all-cause outpatient attendances at the health facilities	Through study completion, 36 months
Secondary	Incidence of confirmed (RDT positive) malaria hospital admissions	Incidence of confirmed (RDT positive) malaria hospital admissions at all health facilities	Through study completion, 36 months
Secondary	Incidence of confirmed (blood smear positive/RDT positive) malaria hospital admissions	Incidence of confirmed (blood smear positive/RDT positive) malaria hospital admissions at all health facilities	Through study completion, 36 months
Secondary	Frequency and severity of drug adverse reactions	Frequency and severity of drug adverse reactions throughout the trial	Through study completion, 36 months
Secondary	Prevalence of macrolide resistance in nasopharyngeal isolates	Prevalence of macrolide resistance in nasopharyngeal isolates	Through study completion, 36 months
Secondary	Prevalence of macrolide resistance in the gut bacteria	Prevalence of macrolide resistance in the gut bacteria	Through study completion, 36 months
Secondary	Proportion of children with protective antibody responses to specific routine EPI immunizations (measles and yellow fever)	Proportion of children with protective antibody responses to specific routine EPI	Through study completion, 36 months