Malaria, Respiratory Infections
Conditions
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: 1. incidence of the primary endpoint during the whole study period 2. attendance at a study health centre with a nonmalaria febrile illness 3. attendance at a study health centre with malaria, 4. the prevalence of moderate anaemia at the end of each malaria transmission season, 5. nutritional status at the end of each malaria transmission season, 6. prevalence of nasopharyngeal carriage with pneumococci and macrolide resistant pneumococci before and at the end of each malaria transmissions season, 7. prevalence of resistance markers to SP at the end of the study, Sample size: 19,200 children (9600 in each country) will be enrolled.
Interventions
DRUGSulphadoxine-Pyrimethamine+ Amodiaquine+ Azithromycin
Sulphadoxine-Pyrimethamine+ Amodiaquine+ Azithromycin 4 rounds during malaria transmission season
DRUGSulphadoxine-pyrimethamine + amodiaquine + placebo azithromycin
Sulphadoxine-pyrimethamine + amodiaquine + placebo azithromycin 4 rounds during malaria transmission season
Sponsors
Malaria Research and Training Center, Bamako, Mali
Institut de Recherche en Sciences de la Sante, Burkina Faso
London School of Hygiene and Tropical Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Months to 59 Months
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| severe morbidity and mortality | 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) | 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
| Measure | 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, |
Other
| Measure | Time frame | Description |
|---|---|---|
| nutritional status | at the end of malaria transmission season in year 1, 2 and 3 | (e) nutritional status at the end of each malaria transmission season, |
| out patient attendance for non malaria febrile illness | from enrolment until the end of malaria transmission season in year 3 | (b) attendance at a study health centre with a febrile illness that is not due to malaria (including acute respiratory infections and diarrhoea), |
| nasopharyngeal carriage | before the administration of first dose of SMC and at the end of malaria transmission season in year 1, 2, and 3 | (f) the prevalence of nasopharyngeal carriage with pneumococci before and at the end of each malaria transmissions season, |
| moderate anaemia | at the end of each malaria transmission season in year 1, 2, and 3 | (d) the prevalence of moderate anaemia (Hb \<8 g/dL) at the end of each malaria transmission season, |
| adverse events | 7 days after administration of SMC in rounds 1, 2, 3 and 4 in year one | solicited adverse events 7 days after administration of SMC+AZ after each round in the year one of the study |
| OPD attendance for malaria | from enrollment until the end of malaria transmission season in year 3 | (c) attendance at a study health centre with RDT or microscopically proven malaria, |
| SP resistance markers | at the end of the malaria transmission season in year 3 | (h) the prevalence of resistance markers to SP in children with Plasmodium falciparum malaria at the end of the study, |
Countries
Burkina Faso, Mali
Outcome results
None listed