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

Phase 4

Completed

Conditions: Postpartum Fever
Postpartum Sepsis
Postpartum Endometritis

Interventions: Drug: Azithromycin and amoxicillin
Drug: Azithromycin
Drug: Placebo

Registration Number: NCT03248297

Lead Sponsor: University of Alabama at Birmingham

Brief Summary: 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.

Detailed 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 756

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Azithromycin + amoxicillin	Azithromycin and amoxicillin	Patients in this arm will receive 1 gram oral azithromycin and 2 grams oral amoxicillin in a single dose.
Azithromycin and amoxicillin placebo	Placebo	Patients in this arm will receive 1 gram oral azithromycin as a single dose and amoxicillin placebo.
Usual Care	Placebo	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)
Azithromycin and amoxicillin placebo	Azithromycin	Patients in this arm will receive 1 gram oral azithromycin as a single dose and amoxicillin placebo.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experienced Composite Peripartum Infection or Death	Up to 6 weeks after delivery	Maternal peripartum infection including chorioamnionitis, endometritis, wound infection/abscess, sepsis, and death

Secondary Outcome Measures

Name	Time	Method
Length of Stay	up to 6 weeks postpartum	Length of stay in days
Number of Participants Who Experienced Fever	up to 6 weeks after delivery	Any fever higher than 38C
Number of Participants Who Experienced Stillbirth	delivery	Any stillbirth
Number of Participants Who Experienced a Maternal Readmission	up to 6 weeks after delivery	Maternal readmission
Number of Participants Who Experienced Hypothermia	up to 6 weeks after delivery	Any hypothermia less than 36C
Number of Participants Who Experienced Other Infection	up to 6 weeks after delivery	Includes Hepatitis B, thyroid infection, vaginal infection, viral infection, leg cellulitis, unknown abdominal infection,malaria
Number of Participants Who Experienced Transfusion	up to 6 weeks after delivery	Blood transfusion
Number of Participants Who Experienced a Clinic Visit	up to 6 weeks after delivery	Clinic visit after discharge
Number of Participants Who Experienced Breast Infection	Up to 6 weeks after delivery	Other infections
Number of Participants Who Needed PP Antibiotic	up to 6 weeks after delivery	Any postpartum antibiotic
Number of Participants Who Experienced Pyelonephritis	Up to hospital discharge	Other Infections