A Trial of Seasonal Malaria Chemoprevention Plus Azithromycin in African Children

NCT ID: NCT02211729

Last Updated: 2018-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 22090 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2017-12-31

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.

Conditions

Malaria; Respiratory Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Seasonal malaria chemoprevention

Sulphadoxine-Pyrimethamine Amodiaquine Placebo Azithromycin

Group Type: ACTIVE_COMPARATOR

Sulphadoxine-pyrimethamine + amodiaquine + placebo azithromycin

Intervention Type: DRUG

Sulphadoxine-pyrimethamine + amodiaquine + placebo azithromycin 4 rounds during malaria transmission season

seasonal malaria chemoprevention plus AZ

Sulphadoxine-Pyrimethamine+ Amodiaquine + Azithromycin 4 rounds during malaria transmission season

Group Type: EXPERIMENTAL

Sulphadoxine-Pyrimethamine+ Amodiaquine+ Azithromycin

Intervention Type: DRUG

Sulphadoxine-Pyrimethamine+ Amodiaquine+ Azithromycin 4 rounds during malaria transmission season

Interventions

Sulphadoxine-Pyrimethamine+ Amodiaquine+ Azithromycin

Sulphadoxine-Pyrimethamine+ Amodiaquine+ Azithromycin 4 rounds during malaria transmission season

Intervention Type: DRUG

Sulphadoxine-pyrimethamine + amodiaquine + placebo azithromycin

Sulphadoxine-pyrimethamine + amodiaquine + placebo azithromycin 4 rounds during malaria transmission season

Intervention Type: DRUG

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

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 59 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Malaria Research and Training Center, Bamako, Mali

OTHER

Sponsor Role: collaborator

Institut de Recherche en Sciences de la Sante, Burkina Faso

OTHER_GOV

Sponsor Role: collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hounde district Hospital

Houndé, , Burkina Faso

Bougouni Koulikoro District hospital

Bougouni, , Mali

Countries

Burkina Faso; Mali

References

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.

Reference Type: DERIVED

PMID: 34644317 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32822362 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30699301 (View on PubMed)

Other Identifiers

MR/K007319/1

Identifier Type: -

Identifier Source: org_study_id