About Azin V Trial
Introduction:
Maternal complications during pregnancy and childbirth present a global challenge, contributing significantly to maternal mortality rates. In 2020 alone, an estimated 287,000 maternal deaths occurred worldwide, equating to approximately 800 women succumbing daily to complications arising from pregnancy and childbirth, equivalent to one death every two minutes. The overwhelming majority of these fatalities, nearly 95%, are concentrated in low-income and middle-income countries (LMICs), with approximately 70% transpiring in sub-Saharan Africa (SSA). A stark illustration is Nigeria, responsible for nearly 30% of global maternal deaths in 2020, recording 82,000 annual fatalities and a staggering 1,047 maternal deaths per 100,000 live births
Maternal deaths are attributed to both direct and indirect obstetric causes. In LMICs, direct obstetric causes account for most fatalities, encompassing complications such as obstetric hemorrhage, preeclampsia, pregnancy-related infections, and unsafe abortion consequences. A study conducted in Nigeria recently revealed that peripartum infection ranks as the second most common cause of maternal death in hospital-based populations
To combat maternal mortality, the World Health Organization (WHO) endorsed antibiotic usage around childbirth in 2015 to prevent and treat maternal peripartum infections in five clinical situations. These encompass women colonized with group B streptococcus, cases of preterm pre-labor rupture of membranes, cesarean deliveries, repair of perineal tears, and manual placental removal. Various trials have explored prophylactic antibiotic use to mitigate maternal sepsis during the peripartum period, particularly in cesarean sections. However, disparities in clinical practice, dosing, antimicrobial availability, and diagnostic capacities have led to implementation challenges, fostering antibiotic resistance and side effects
Azithromycin, an affordable broad-spectrum macrolide antibiotic effective against causative bacteria of maternal sepsis in Sub Saharan Africa, presents a promising alternative. Its extended half-life, high placental tissue antibiotic levels, ease of administration, lower cost, enhanced compliance, and favorable pharmacokinetic profile position it favorably for preventing maternal infections during labor, premature rupture of membranes PPROM, and planned cesarean delivery. Despite concerns about macrolide resistance linked to its widespread use, this resistance appears transient
Though the WHO recommends routine antibiotic prophylaxis for operative vaginal births, investigations into azithromycin’s role in averting maternal infections during vaginal births have been conducted. A single oral dose of azithromycin has demonstrated safety, cost-effectiveness, and efficacy in reducing maternal sepsis during vaginal births in LMICs. Nevertheless, its impact in a country like Nigeria, with its staggering maternal mortality rates and sepsis prevalence, remains unclear.
Furthermore, while evidence exists regarding the challenges and enablers of implementing interventions to enhance appropriate antibiotic use in LMICs, there is a paucity of data concerning factors influencing the effects and implementation of azithromycin during vaginal births. This knowledge gap hinders the development of effective strategies to implement azithromycin during vaginal births, particularly in SSA, and hampers efforts to tailor WHO recommendations
Moreover, assessing the cost-effectiveness of azithromycin prophylaxis in planned vaginal births, especially in resource-scarce environments, is crucial. This evaluation is pivotal for sustainable adoption in Nigeria, given the nation’s fragile health financing framework marked by low public investment and high out-of-pocket expenditures, often resulting in healthcare-driven impoverishment.
Addressing maternal complications during pregnancy and childbirth is an urgent global priority. The potential of azithromycin as a preventive measure against maternal infections during vaginal births is promising, especially in regions burdened with high maternal mortality rates. However, an in-depth understanding of its implementation challenges, cost-effectiveness, and impact on maternal health is essential for meaningful change and reduction of maternal mortality rates, particularly in countries like Nigeria.
Aims & Objectives
- Assess the clinical effectiveness and safety of intrapartum administration of oral azithromycin compared to current routine health-facility practice (usual care) for the prevention of maternal sepsis among pregnant women undergoing vaginal birth across multiple health facilities in Nigeria.
- Estimate incremental costs and cost-effectiveness of oral azithromycin compared to current standard of care in preventing maternal sepsis among women undergoing vaginal birth across multiple health facilities in Nigeria.
- Assess the effectiveness of skilled health personnel (SHP)-tailored strategies to enhance the implementation and adoption of oral azithromycin as part of a sepsis prevention protocol during vaginal birth across multiple health facilities in Nigeria.