Abstrakti
Background: Mass drug administration (MDA) of azithromycin (AZI) has been shown to reduce under-5 mortality in some but not all sub-Saharan African settings. A large-scale cluster-randomized trial conducted in Malawi, Niger, and Tanzania suggested that the effect differs by country, may be stronger in infants, and may be concentrated within the first 3 months after treatment. Another study found no effect when azithromycin was given concomitantly with seasonal malaria chemoprevention (SMC). Given the observed heterogeneity and possible effect modification by other co-interventions, further trials are needed to determine the efficacy in additional settings and to determine the most effective treatment regimen. Methods: LAKANA stands for Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin. The LAKANA trial is designed to address the mortality and health impacts of 4 or 2 annual rounds of azithromycin MDA delivered to 1–11-month-old (29–364 days) infants, in a high-mortality and malaria holoendemic Malian setting where there is a national SMC program. Participating villages (clusters) are randomly allocated in a ratio of 3:2:4 to three groups: placebo (control):4-dose AZI:2-dose AZI. The primary outcome measured is mortality. Antimicrobial resistance (AMR) will be monitored closely before, during, and after the intervention and both among those receiving and those not receiving MDA with the study drugs. Other outcomes, from a subset of villages, comprise efficacy outcomes related to morbidity, growth and nutritional status, outcomes related to the mechanism of azithromycin activity through measures of malaria parasitemia and inflammation, safety outcomes (AMR, adverse and serious adverse events), and outcomes related to the implementation of the intervention documenting feasibility, acceptability, and economic aspects. The enrolment commenced in October 2020 and is planned to be completed by the end of 2022. The expected date of study completion is December 2024. Discussion: If LAKANA provides evidence in support of a positive mortality benefit resulting from azithromycin MDA, it will significantly contribute to the options for successfully promoting child survival in Mali, and elsewhere in sub-Saharan Africa. Trial registration: ClinicalTrials.gov NCT04424511. Registered on 11 June 2020.
| Alkuperäiskieli | Englanti |
|---|---|
| Artikkeli | 5 |
| Julkaisu | Trials |
| Vuosikerta | 24 |
| DOI - pysyväislinkit | |
| Tila | Julkaistu - 2023 |
| OKM-julkaisutyyppi | A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä |
Rahoitus
The LAKANA trial is funded by the Bill & Melinda Gates Foundation (Seattle, WA, USA), Grant Agreement Investment ID: INV-003354. The study design was developed in collaboration with the funder and involved an external advisory group. The funder has no role during the execution of the study and will have no role during the analysis, interpretation of the data, or the decision to submit results. The LAKANA Trial team would like to thank all national and local leaders in Mali who are facilitating trial activities and the children and their families who have participated in the trial to date. The authors gratefully acknowledge the work and dedication of all study staff at all participating sites. The authors thank Pfizer Inc. for donating azithromycin and placebo. The authors appreciate the support and guidance of the DSMB members, Dr. Robert Black (chair), Dr. Julia Bielicki, Dr. Alassane Dicko, Dr. Queen Dube, and Dr. Paul Milligan. The authors would like to thank the TAG members, Dr. Tom Lietman (chair), Dr. Anthony Solomon, and Dr. Karen Kotloff, for their guidance on trial implementation. Group authorship A list of members of the LAKANA Trial Team is as follows:First name Last name Laura Adubra Dagmar Alber Per Ashorn Ulla Ashorn Yin Bun Cheung Elaine Cloutman-Green Fatoumata Diallo Camilla Ducker Riku Elovainio Yue-Mei Fan Lily Gates Gwydion Gruffudd Tiia Haapaniemi Fadima Haidara Lotta Hallamaa Rikhard Ihamuotila Nigel Klein Juho Luoma Owen Martell Samba Sow Taru Vehmasto Tampere University acts as the project coordinator and trial sponsor organization. The sponsor bears responsibility for ensuring that all activities implemented during the trial are conducted as recommended by ICH-GCP guidelines. The sponsor is responsible for coordinating data management, monitoring, and reporting and for result dissemination. The sponsor acts as a project link and reporting organization with regard to the funder and other external stakeholders.
Julkaisufoorumi-taso
- Jufo-taso 1
!!ASJC Scopus subject areas
- Medicine (miscellaneous)
- Pharmacology (medical)
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