Clinical trial NCT02211729: A Trial of Seasonal Malaria Chemoprevention Plus Azithromycin in African Children
Official title: A Trial of Seasonal Malaria Chemoprevention Plus Azithromycin in African Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria
Respiratory Infections
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Malaria Research and Training Center, Bamako, Mali
name: Institut de Recherche en Sciences de la Sante, Burkina Faso
First posted: 2014-08-07
Enrollment: 22090
Sex: ALL
Minimum age (years): 3
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: severe morbidity and mortality
timeFrame: 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 outcomes:
measure: macrolide resistant pneumococci carriage
timeFrame: before administration of first dose of SMC and at the end of malaria transmission season in year 1, 2 and 3,
Other outcomes:
measure: out patient attendance for non malaria febrile illness
timeFrame: from enrolment until the end of malaria transmission season in year 3
measure: OPD attendance for malaria
timeFrame: from enrollment until the end of malaria transmission season in year 3
measure: moderate anaemia
timeFrame: at the end of each malaria transmission season in year 1, 2, and 3
measure: nutritional status
timeFrame: at the end of malaria transmission season in year 1, 2 and 3
measure: nasopharyngeal carriage
timeFrame: before the administration of first dose of SMC and at the end of malaria transmission season in year 1, 2, and 3
measure: SP resistance markers
timeFrame: at the end of the malaria transmission season in year 3
measure: adverse events
timeFrame: 7 days after administration of SMC in rounds 1, 2, 3 and 4 in year one
Locations:
city: Hounde
country: Burkina Faso
facility: Hounde district Hospital
city: Bougouni
country: Mali
facility: Bougouni Koulikoro District hospital
Study officials:
References:
citation: Hema-Ouangraoua S, Tranchot-Diallo J, Zongo I, Kabore NF, Nikiema F, Yerbanga RS, Tinto H, Chandramohan D, Ouedraogo GA, Greenwood B, Ouedraogo JB. Impact of mass administration of azithromycin as a preventive treatment on the prevalence and resistance of nasopharyngeal carriage of Staphylococcus aureus. PLoS One. 2021 Oct 13;16(10):e0257190. doi: 10.1371/journal.pone.0257190. eCollection 2021.
citation: Cairns ME, Sagara I, Zongo I, Kuepfer I, Thera I, Nikiema F, Diarra M, Yerbanga SR, Barry A, Tapily A, Coumare S, Milligan P, Tinto H, Ouedraogo JB, Chandramohan D, Greenwood B, Djimde A, Dicko A. Evaluation of seasonal malaria chemoprevention in two areas of intense seasonal malaria transmission: Secondary analysis of a household-randomised, placebo-controlled trial in Hounde District, Burkina Faso and Bougouni District, Mali. PLoS Med. 2020 Aug 21;17(8):e1003214. doi: 10.1371/journal.pmed.1003214. eCollection 2020 Aug.
citation: Chandramohan D, Dicko A, Zongo I, Sagara I, Cairns M, Kuepfer I, Diarra M, Barry A, Tapily A, Nikiema F, Yerbanga S, Coumare S, Thera I, Traore A, Milligan P, Tinto H, Doumbo O, Ouedraogo JB, Greenwood B. Effect of Adding Azithromycin to Seasonal Malaria Chemoprevention. N Engl J Med. 2019 Jun 6;380(23):2197-2206. doi: 10.1056/NEJMoa1811400. Epub 2019 Jan 30.