A Trial of Seasonal Malaria Chemoprevention Plus Azithromycin in African Children

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to determine whether addition of azithromycin (AZ) to Seasonal Malaria Chemoprevention (SMC) using sulphadoxine/pyrimethamine (SP) +amodiaquine (AQ) will provide an additional reduction in deaths and severe illness in young African children. The secondary objectives include an assessment of the safety and cost-effectiveness of the addition of AZ to SMC with SP+AQ. This a double blind, randomised, placebo controlled trial. The unit of randomisation will be the household. Children aged 3 - 59 months will be randomised to receive four cycles of either SP+AQ+AZ or SP+AQ+ placebo at monthly intervals during the peak malaria transmission season. Study Sites: Hounde district in Burkina Faso and in Bougouni district, Mali. Children of 3-59 months of age at the start of each period of drug administration will be eligible for inclusion in the trial provided that parental consent is obtained. Children with a severe, chronic illness or known allergy to one of the study drugs will be excluded. Primary endpoint: Incidence of the combination of death or hospital admission for at least 24 hours, not due to trauma or elective surgery during the intervention period Secondary endpoints: incidence of the primary endpoint during the whole study period attendance at a study health centre with a nonmalaria febrile illness attendance at a study health centre with malaria, the prevalence of moderate anaemia at the end of each malaria transmission season, nutritional status at the end of each malaria transmission season, prevalence of nasopharyngeal carriage with pneumococci and macrolide resistant pneumococci before and at the end of each malaria transmissions season, prevalence of resistance markers to SP at the end of the study, Sample size: 19,200 children (9600 in each country) will be enrolled.

Official Title
-----------------
A Trial of Seasonal Malaria Chemoprevention Plus Azithromycin in African Children

Conditions
-----------------
Malaria, Respiratory Infections

Intervention / Treatment
-----------------
* Drug: Sulphadoxine-Pyrimethamine+ Amodiaquine+ Azithromycin
* Drug: Sulphadoxine-pyrimethamine + amodiaquine + placebo azithromycin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children of either sex aged 3-59 months of age at the start of each period of drug administration parental consent is obtained. Exclusion Criteria: a severe, chronic illness, a known allergy to one of the study drugs. HIV+ children on cotrimoxazole prophylaxis

Ages Eligible for Study
-----------------
Minimum Age: 3 Months
Maximum Age: 59 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Seasonal malaria chemoprevention<br>Sulphadoxine-Pyrimethamine Amodiaquine Placebo Azithromycin | Drug: Sulphadoxine-pyrimethamine + amodiaquine + placebo azithromycin<br>* Sulphadoxine-pyrimethamine + amodiaquine + placebo azithromycin 4 rounds during malaria transmission season<br>|
| Experimental: seasonal malaria chemoprevention plus AZ<br>Sulphadoxine-Pyrimethamine+ Amodiaquine + Azithromycin 4 rounds during malaria transmission season | Drug: Sulphadoxine-Pyrimethamine+ Amodiaquine+ Azithromycin<br>* Sulphadoxine-Pyrimethamine+ Amodiaquine+ Azithromycin 4 rounds during malaria transmission season<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| severe morbidity and mortality | Incidence of the combination of death or hospital admission for at least 24 hours, not due to trauma or elective surgery during the intervention period. | from the time of enrolment upto the end of malaria transmission in year 3 ( the person time at risk will be restricted to three malaria transmission seasons) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| macrolide resistant pneumococci carriage |  | before administration of first dose of SMC and at the end of malaria transmission season in year 1, 2 and 3, |