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

NCT03248297 | Completed Phase 4 Results DMC

• 1 other identifier: CHI UAB MISP # 54628
• Study Type: interventional
• Target: 756
• Locations: 1 country
• Sites: 1

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.

Conditions

Postpartum Sepsis; Postpartum Endometritis; Postpartum Fever

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Number of Participants Who Experienced Pyelonephritis

  Up to hospital discharge

• Number of Participants Who Experienced Breast Infection

  Up to 6 weeks after delivery

• Number of Participants Who Experienced Other Infection

  up to 6 weeks after delivery

• Number of Participants Who Experienced Fever

  up to 6 weeks after delivery

• Number of Participants Who Experienced Hypothermia

  up to 6 weeks after delivery

Study Arms (3)

Azithromycin and amoxicillin placebo

EXPERIMENTAL

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

Drug: Azithromycin; Drug: Placebo

Azithromycin + amoxicillin

EXPERIMENTAL

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

Drug: Azithromycin and amoxicillin

Usual Care

PLACEBO COMPARATOR

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)

Drug: Placebo

Interventions

Azithromycin DRUG

Azithromycin tablet

Azithromycin and amoxicillin placebo

Azithromycin and amoxicillin DRUG

azithromycin and amoxicillin

Also known as: azithromycin, amoxicillin

Azithromycin + amoxicillin

Placebo DRUG

Placebo tablet

Azithromycin and amoxicillin placebo; Usual Care

Eligibility Criteria

• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Women ≥ 37 weeks' viable singleton or twin gestation in labor planning a vaginal delivery with
• Prolonged membrane rupture (≥8 hours) or
• Prolonged labor (≥18 hours).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Cameroon Baptist Convention Health Services

Bamenda, Cameroon

Location

Related Publications (5)

• 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.

  PMID: 10196487 BACKGROUND

• 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.

  PMID: 10511234 BACKGROUND

• 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.

  PMID: 28076707 BACKGROUND

• 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/

  PMID: 26598777 BACKGROUND

• 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.

  PMID: 34619734 DERIVED

MeSH Terms

Conditions

Puerperal Infection

Interventions

Azithromycin; Amoxicillin

Condition Hierarchy (Ancestors)

Pregnancy Complications, Infectious; Infections; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Alan Tita, MD
• Organization: University of Alabama at Birmingham

atita@uab.edu

205-934-5612

Study Officials

• Alan Tita, MD, PhD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director

Model Details: Randomized Controlled Trial

Study Record Dates

• First Submitted: July 25, 2017
• First Posted: August 14, 2017
• Study Start: January 12, 2018
• Primary Completion: May 15, 2020
• Study Completion: October 1, 2020
• Last Updated: July 18, 2022
• Results First Posted: July 18, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)