Pre-delivery administration of azithromycin to prevent neonatal sepsis and death: a phase iii double-blind randomized clinical trial (PregnAnZI-2 trial)

Authors

  • Bully Camara Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Joel D. Bognini Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa
  • Usman N. Nakakana Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Athanase M. Some Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa
  • Isatou Jagne Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Marc C. Tahita Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa
  • Nathalie Beloum Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Fatoumata Sillah Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Madikoi Danso Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Joquina C. Jones Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Shashu Graves Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Pauline Getanda Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Toussaint Rouamba Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa
  • Ebrahim Ndure Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Hien S. Franck Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa
  • Sawadogo Y. Edmond Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa
  • Yusupha Njie Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Bai L. Dondeh Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Nassa G. J. Wilfried Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa
  • Abdoulie Bojang Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Garba Zakaria Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa
  • Christian Bottomley London School of Hygiene and Tropical Medicine, London, United Kingdom
  • Umberto D’Alessandro Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia
  • Halidou Tinto Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa
  • Anna Roca Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

DOI:

https://doi.org/10.18203/2349-3259.ijct20220110

Keywords:

Azithromycin, Neonatal sepsis, Neonatal mortality, Bacterial infections, Randomized clinical trial, Bacterial carriage, Sub-Saharan Africa

Abstract

Background: Despite reduction in the risk of under-5 mortality in the last decade and a half, neonatal deaths have remained stable globally. Gram-positive bacterial infections are leading causes of neonatal sepsis and death. Because the mother is an important source for bacterial transmission to babies during the perinatal period, interventions that lower risk of transmission can potentially reduce invasive bacterial infections. The primary objective of the trial will assess the effect of intrapartum azithromycin on neonatal sepsis and mortality. Secondary objectives include the impact of the intervention on prevalence of carriage and resistance, puerperal infections, and infant growth.

Methods: This is a phase III, double-blinded, placebo-controlled randomized trial in which 12,000 women in labour are randomized to either a single dose of 2 g of oral azithromycin (AZI) or placebo in The Gambia and Burkina Faso. Mother/newborn pairs are followed-up at 28-days post-delivery to assess health and mortality. Passive visits are conducted to collect adverse events including hospitalizations. When clinically indicated, samples are collected for assessment of neonatal and puerperal sepsis. A cohort of 250 mother/newborn pair per country have been included in the carriage sub-study to assess bacterial colonization at day 0, 6, 28 and 4 months. Children of the first 1000 mothers recruited in each country are followed-up at 6 and 12 months for anthropometric assessments.

Conclusions: If successful, this simple implementable intervention has the potential to achieve wide coverage in Sub-Saharan Africa (SSA) where low-cost interventions to reduce neonatal sepsis and mortality and morbidity in mothers are urgently needed.

Trial registration: The trial was registered at ClinicalTrials.gov: NCT03199547.

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Author Biographies

Bully Camara, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Disease Control and Elimination Theme

Clinical Trial Coordinator / Clinician

Joel D. Bognini, Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa

Clinical Trial Coordinator/Clinician

Usman N. Nakakana, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Disease Control and Elimination Theme

Research Clinician/Paediatrician

Athanase M. Some, Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa

Research Clinician/Paediatrician

Isatou Jagne, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Disease Control and Elimination Theme

Higher Scientific Officer

Marc C. Tahita, Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa

PhD Laboratory Scientist

Nathalie Beloum, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Disease Control and Elimination Theme

Research Clinician

Fatoumata Sillah, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Disease Control and Elimination Theme

Research Clinician

Madikoi Danso, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Disease Control and Elimination Theme

Research Clinician

Joquina C. Jones, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Disease Control and Elimination Theme

Research Clinician

Shashu Graves, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Disease Control and Elimination Theme

Research Clinician

Pauline Getanda, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Disease Control and Elimination Theme

PhD Student

Toussaint Rouamba, Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa

Medical Doctor/Data Manager

Ebrahim Ndure, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Data Management

Data Manager

Hien S. Franck, Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa

Data Manager

Sawadogo Y. Edmond, Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa

Research Clinician

Yusupha Njie, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Data Management

Senior Data Manager

Bai L. Dondeh, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Data Management

Head of Data Management

Nassa G. J. Wilfried, Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa

Research Clinician

Abdoulie Bojang, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Disease Control and Elimination Theme

Post Doctoral Microbiologist

Garba Zakaria, Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa

Lab Scientific Officer

Christian Bottomley, London School of Hygiene and Tropical Medicine, London, United Kingdom

Department of Infectious Disease Epidemiology

Associate Professor (Medical Statistics and Epidemiology)Trial Statistician

Umberto D’Alessandro, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Unit Director MRCG at LSHTM

Theme Leader Disease Control and Elimination Theme

Halidou Tinto, Clinical Research Unit of Nanoro (CRUN), Burkina Faso, West Africa

Regional Director of the Institute for Health Sciences Research (IRSS) in Nanoro

Head, Clinical Research Unit of Nanoro (CRUN)

Principal Investigator PregnAnZI-2 Trial, Burkina Faso

Anna Roca, Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM), The Gambia

Professor of Epidemiology,

Chief Investigator and Principal Investigator The Gambia, PregnAnZI-2 Trial

Theme Leader Disease Control and Elimination Theme

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Published

2022-01-25

How to Cite

Camara, B., Bognini, J. D., Nakakana, U. N., Some, A. M., Jagne, I., Tahita, M. C., Beloum, N., Sillah, F., Danso, M., Jones, J. C., Graves, S., Getanda, P., Rouamba, T., Ndure, E., Franck, H. S., Edmond, S. Y., Njie, Y., Dondeh, B. L., Wilfried, N. G. J., Bojang, A., Zakaria, G., Bottomley, C., D’Alessandro, U., Tinto, H., & Roca, A. (2022). Pre-delivery administration of azithromycin to prevent neonatal sepsis and death: a phase iii double-blind randomized clinical trial (PregnAnZI-2 trial). International Journal of Clinical Trials, 9(1), 34–44. https://doi.org/10.18203/2349-3259.ijct20220110