Clinical trial NCT03248297: Antibiotic Prophlaxis for High-risk Laboring Women in Low Income Countries
Official title: Azithromycin With or Without Amoxicillin to Prevent Peripartum Infection and Sepsis in Laboring High-risk Women: 3-Arm RCT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postpartum Sepsis
Postpartum Endometritis
Postpartum Fever
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-08-14
Enrollment: 756
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Controlled Trial
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Experienced Composite Peripartum Infection or Death
timeFrame: Up to 6 weeks after delivery
Secondary outcomes:
measure: Number of Participants Who Experienced Pyelonephritis
timeFrame: Up to hospital discharge
measure: Number of Participants Who Experienced Breast Infection
timeFrame: Up to 6 weeks after delivery
measure: Number of Participants Who Experienced Other Infection
timeFrame: up to 6 weeks after delivery
measure: Number of Participants Who Experienced Fever
timeFrame: up to 6 weeks after delivery
measure: Number of Participants Who Experienced Hypothermia
timeFrame: up to 6 weeks after delivery
measure: Number of Participants Who Needed PP Antibiotic
timeFrame: up to 6 weeks after delivery
measure: Number of Participants Who Experienced Transfusion
timeFrame: up to 6 weeks after delivery
measure: Number of Participants Who Experienced Stillbirth
timeFrame: delivery
measure: Length of Stay
timeFrame: up to 6 weeks postpartum
measure: Number of Participants Who Experienced a Clinic Visit
timeFrame: up to 6 weeks after delivery
measure: Number of Participants Who Experienced a Maternal Readmission
timeFrame: up to 6 weeks after delivery
Other outcomes:
Locations:
city: Bamenda
country: Cameroon
facility: Cameroon Baptist Convention Health Services
Study officials:
affiliation: University of Alabama at Birmingham
name: Alan Tita, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control. 1999 Apr;27(2):97-132; quiz 133-4; discussion 96.
citation: ASHP Therapeutic Guidelines on Antimicrobial Prophylaxis in Surgery. American Society of Health-System Pharmacists. Am J Health Syst Pharm. 1999 Sep 15;56(18):1839-88. doi: 10.1093/ajhp/56.18.1839. No abstract available.
citation: Tita ATN, Boggess K, Saade G. Adjunctive Azithromycin Prophylaxis for Cesarean Delivery. N Engl J Med. 2017 Jan 12;376(2):182. doi: 10.1056/NEJMc1614626. No abstract available.
citation: WHO Recommendations for Prevention and Treatment of Maternal Peripartum Infections. Geneva: World Health Organization; 2015. Available from http://www.ncbi.nlm.nih.gov/books/NBK327079/
citation: Subramaniam A, Ye Y, Mbah R, Mbunwe DM, Pekwarake S, Bunwi EY, Fondzeyuf A, Ngong MG, Dionne-Odom J, Harper LM, Jauk VC, Carlo WA, Halle-Ekane G, Szychowski JM, Tih P, Tita AT. Single Dose of Oral Azithromycin With or Without Amoxicillin to Prevent Peripartum Infection in Laboring, High-Risk Women in Cameroon: A Randomized Controlled Trial. Obstet Gynecol. 2021 Nov 1;138(5):703-713. doi: 10.1097/AOG.0000000000004565.