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

Postpartum Endometritis Clinical Trial

Official title:

Azithromycin With or Without Amoxicillin to Prevent Peripartum Infection and Sepsis in Laboring High-risk Women: 3-Arm RCT

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03248297
• Other study ID #: CHI UAB MISP # 54628
• Status: Completed
• Phase: Phase 4
• Start date: January 12, 2018
• Est. completion date: October 1, 2020

Study information

• Verified date: March 2022
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 756
• Est. completion date: October 1, 2020
• Est. primary completion date: May 15, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Endometritis
• Postpartum Endometritis
• Postpartum Fever
• Postpartum Sepsis
• Puerperal Infection
• Sepsis

Intervention

Drug:
• Azithromycin
Azithromycin tablet
• Azithromycin and amoxicillin
azithromycin and amoxicillin
• Placebo
Placebo tablet

Locations

Country	Name	City	State
Cameroon	Cameroon Baptist Convention Health Services	Bamenda

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

Cameroon, 

References & Publications (4)

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. Review. — View 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. — View 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. — View Citation

WHO. WHO recommendations for prevention and treatment of maternal peripartum infections. Sept 2015 http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/peripartum-infections-guidelines/en/

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Experienced Composite Peripartum Infection or Death	Maternal peripartum infection including chorioamnionitis, endometritis, wound infection/abscess, sepsis, and death	Up to 6 weeks after delivery
Secondary	Number of Participants Who Experienced Pyelonephritis	Other Infections	Up to hospital discharge
Secondary	Number of Participants Who Experienced Breast Infection	Other infections	Up to 6 weeks after delivery
Secondary	Number of Participants Who Experienced Other Infection	Includes Hepatitis B, thyroid infection, vaginal infection, viral infection, leg cellulitis, unknown abdominal infection,malaria	up to 6 weeks after delivery
Secondary	Number of Participants Who Experienced Fever	Any fever higher than 38C	up to 6 weeks after delivery
Secondary	Number of Participants Who Experienced Hypothermia	Any hypothermia less than 36C	up to 6 weeks after delivery
Secondary	Number of Participants Who Needed PP Antibiotic	Any postpartum antibiotic	up to 6 weeks after delivery
Secondary	Number of Participants Who Experienced Transfusion	Blood transfusion	up to 6 weeks after delivery
Secondary	Number of Participants Who Experienced Stillbirth	Any stillbirth	delivery
Secondary	Length of Stay	Length of stay in days	up to 6 weeks postpartum
Secondary	Number of Participants Who Experienced a Clinic Visit	Clinic visit after discharge	up to 6 weeks after delivery
Secondary	Number of Participants Who Experienced a Maternal Readmission	Maternal readmission	up to 6 weeks after delivery