Improving Care through Azithromycin Research for Infants in Africa (ICARIA)
The general objective of ICARIA is to evaluate the impact of azithromycin administered through the Expanded Program on Immunization in addition to IPTi-SP on all-cause mortality at 18 months of age in Sierra Leone.
And the specific objectives of this project are:
- To evaluate the effect on all-cause mortality up to the age of 18 months of adding AZi at 6 weeks, 9 and 15 months of age to IPTi-SP administered at 10,14 weeks, 6, 9, 12 and 15 months of age alongside routine EPI immunizations
- To assess adverse events associated with AZi administration
- To assess the potential development of resistance to macrolides
- To determine the potential interactions between AZi and specific routine EPI immunizations
- To determine the effect of the interventions on malaria-related indicators
- To assess the potential risk of development of SP parasite resistance
- To examine the health system implications related to the addition of AZi to the EPI and its acceptability by health providers and participants
Half of the 5.4 million children under 5 years of age (U5) who die in the world annually live in the African region where falciparum malaria is a major cause of death. Intermittent preventive treatment of malaria in infants (IPTi), consisting of the administration of sulphadoxine-pyrimethamine to infants, is a safe, efficacious and cost-effective intervention in reducing malaria. Despite the WHO recommendation (2010) to administer IPTi alongside routine vaccinations in areas of high to moderate perennial transmission, IPTi is not implemented in most of African malaria endemic countries. Recent studies in some African countries showed that azithromycin (AZi)– is associated with a significant reduction in child mortality when used for mass drug administration in the elimination of trachoma. Evaluation of the impact on mortality reduction of the addition of AZi to IPTi (ITPi+) and assessment of bottlenecks for IPTi scale-up are needed before promoting their large scale-up.
An individually randomized double-blinded placebo-controlled superiority clinical trial will be carried out to evaluate the impact of azithromycin administered through the Expanded Program on Immunization on all-cause mortality at 18 months of age. AZi will be administrated in (20,000) infants exposed to high malaria endemicity and mortality burden in Sierra Leone (SL). This approach will enable to obtain conclusive evidence of the effect of IPTi together with AZi in U5’s mortality reduction and address knowledge and implementation gaps to scale-up ITPi/IPTi+: 1.
Evaluation of the Expanded Program on Immunisation (EPI) as a delivery channel to ensure the long-term sustainability of interventions targeted to young children 2. Evaluation of knowledge gaps related to the effect of AZi as a tool to reduce infant mortality, such as: a) potential development of macrolide resistance; b) understanding the mechanisms of action of AZi in reducing mortality; c) Ascertaining the seasonality effect on mortality and the frequency of adverse events; and d) Determining the potential interactions of the drug with the vaccines routinely given through the EPI system.
ClinicalTrials.gov Identifier: NCT04235816
Study Type: Interventional
Study Phase: Phase 3
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Intervention Model Description: 2-arm individually randomized placebo-controlled clinical trial of AZi administration in young children from Sierra Leone.
- Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description: Quadruple: (Participant, Care Provider, Investigator, Outcomes Assessor)
- Primary Purpose: Prevention