Antibiotic Prophlaxis for High-risk Laboring Women in Low Income Countries

The University of Alabama at Birmingham

Status and phase: Completed; Phase 4

Conditions: Postpartum Endometritis; Postpartum Sepsis; Postpartum Fever

Treatments: Drug: Azithromycin; Drug: Placebo; Drug: Azithromycin and amoxicillin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03248297

CHI UAB MISP # 54628

Details and patient eligibility

About

This study, performed over a course of 3 years in 5 collaborating hospitals in Cameroon, Africa, will randomize 750 women in labor with prolonged rupture of membranes ≥ 8 hours or prolonged labor ≥ 18 hours to identical oral regimens of 1 gram of azithromycin, 1 gram of azithromycin+2 grams of amoxicillin or placebo. Women will be followed to ascertain maternal infectious outcomes and perinatal outcomes.

Full description

This 3-arm study is a large randomized clinical trial designed to evaluate the comparative effectiveness and safety of single dose oral azithromycin or combined azithromycin+amoxicillin compared to placebo for the prevention of peripartum infections and sepsis in laboring women. We have previously shown the effectiveness of azithromycin for extended spectrum antibiotic prophylaxis in addition to the standard cephalosporin alone for reduction of post-cesarean infections. In LICs, the fraction of maternal infection and sepsis from cesarean delivery is minimal. Therefore, it is necessary to evaluate strategies aimed at reducing these morbidities in women who have vaginal births. There is an increased risk of infection in women who have prolonged labor or prolonged rupture of membranes. Drawing from our findings with azithromycin-based extended antibiotic prophylaxis for cesarean delivery, we propose to adapt the intervention and evaluate a single oral dose of azithromycin (with or without oral amoxicillin) to prevent maternal peripartum infection and sepsis. This study, performed over a course of 3 years in 5 collaborating hospitals in Cameroon, Africa, will randomize 750 women in labor with prolonged rupture of membranes ≥ 8 hours or prolonged labor ≥18 hours to 1 gram of oral azithromycin, 1 gram of azithromycin+2 grams of amoxicillin, compared to usual care (placebo). Women will be followed to ascertain maternal infectious outcomes and perinatal outcomes.

Enrollment: 756 patients

Sex: Female

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Women ≥ 37 weeks' viable singleton or twin gestation in labor planning a vaginal delivery with

  1. Prolonged membrane rupture (≥8 hours) or
  2. Prolonged labor (≥18 hours).

Exclusion criteria

• Clinical chorioamnionitis or any other active bacterial infection (e.g. pyelonephritis, pneumonia, abscess) at time of randomization: because standard antibiotic therapy for these conditions may confound trial intervention.
• Allergy to azithromycin or amoxicillin
• Plan for cesarean delivery prior to enrollment
• Fetal demise or major congenital anomaly: Major congenital anomalies may confound assessment of neonatal outcomes and every attempt will be made up front to exclude them from randomization. However, some unrecognized fetal anomalies may inevitably be randomized. These will not be excluded post-randomization from the primary (maternal outcome) analysis; they will be taken into consideration in the secondary analyses of neonatal outcomes.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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756 participants in 3 patient groups, including a placebo group

Azithromycin and amoxicillin placebo

Experimental group

Description:

Patients in this arm will receive 1 gram oral azithromycin as a single dose and amoxicillin placebo.

Treatment:

Drug: Azithromycin

Drug: Placebo

Azithromycin + amoxicillin

Experimental group

Description:

Patients in this arm will receive 1 gram oral azithromycin and 2 grams oral amoxicillin in a single dose.

Treatment:

Drug: Azithromycin and amoxicillin

Usual Care

Placebo Comparator group

Description:

This arm will consist of routine care at the clinical sites (which is usually no antibiotic). They will receive placebo (for azithromycin) and placebo (for amoxicillin)

Treatment:

Drug: Placebo