Erythromycin Versus Azithromycin for Preterm Prelabor Rupture of Membranes (PRACET)

Erythromycin Versus Azithromycin for Preterm Prelabor Rupture of Membranes: A Cluster Randomized Comparative Effectiveness Trial

The goal of this study is to help identify the best antibiotic treatment for pregnant people when their water breaks prematurely (a condition abbreviated as PPROM). Current practice is to attempt to maintain the pregnancy until at least 34 weeks gestational age, when the risks of prematurity to the baby are lessened. Research shows that antibiotics help the pregnancy last longer, but there have been limited studies about which combination works best. Currently, both azithromycin and erythromycin are accepted antibiotic treatments, in addition to ampicillin and amoxicillin. Participants diagnosed with PPROM will be randomized to receive ampicillin and amoxicillin plus either azithromycin or erythromycin, in addition to the care they would normally receive. Studying these two drugs will help decide the best care for future patients with PPROM.

Study Overview

• Status: Recruiting
• Conditions: Premature Rupture of Membrane
• Intervention / Treatment: Drug: Erythromycin; Drug: Azithromycin

Detailed Description

Preterm pre-labor rupture of membranes (PPROM) complicates 3% of pregnancies and accounts for one-fourth to one-third of preterm births. PPROM is associated with significant maternal and neonatal morbidities, including chorioamnionitis, endometritis, neonatal sepsis, prematurity-related pathologies. In the absence of labor or indication for immediate delivery, patients who present at less than 34 weeks gestational age are treated with antibiotics to prolong pregnancy until 34 weeks when the risks of prematurity are decreased. Based on randomized trials, both the American College of Obstetrics and Gynecology (ACOG) and the Society of Maternal Fetal Medicine (SMFM) recommend IV ampicillin and IV erythromycin for 2 days, followed by an oral regimen of amoxicillin and erythromycin for 5 days. Due to the recent limited availability of erythromycin, azithromycin has been used a substitute. There have been observational studies showing no difference in duration of pregnancy between azithromycin and erythromycin, however no randomized controlled trial has been carried out to our knowledge. This study performs a cluster randomized controlled trial to examine the efficacy of azithromycin versus erythromycin as a component of the "latency antibiotics" used to prolong pregnancy in PPROM patients.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Antonio Saad, MD, MBA; Phone Number: 7037766040; Email: antonio.saad@inova.org
• Study Contact Backup: Name: Ellen M Murrin, DO; Phone Number: 7037766040; Email: ellen.murrin@inova.org

Study Locations

• United States
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Recruiting
      • Inova Fairfax Medical Campus
      • Contact: Ellen M Murrin, DO; Phone Number: 703-776-6040; Email: ellen.murrin@inova.org
      • Principal Investigator: Antonio Saad, MD, MBA
      • Contact: Antonio Saad, MD, MBA; Email: antonio.saad@inova.org
      • Sub-Investigator: Ellen M Murrin, DO
    • Norfolk, Virginia, United States, 23507
      • Recruiting
      • Eastern Viriginia Medical School
      • Contact: Tetsuya Kawakita, MD; Phone Number: 757-446-7900; Email: kawakit@evms.edu
      • Contact: Kristin Ayers, MPH; Phone Number: 7574460579; Email: ayerskl@evms.edu
      • Principal Investigator: Tetsuya Kawakita, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnancy at 22 weeks 0 days to 32 weeks 6 days of gestation.
• Rupture of membranes confirmed by biochemical testing.
• Membrane rupture within the past 36 hours.
• Cervical dilation 3 cm or less and 4 or fewer contractions within 60-minutes at the time of admission.
• Age ≥18 and <50 years.

Exclusion Criteria:

• Non-reassuring fetal heart tracing, vaginal bleeding, chorioamnionitis or any indication for delivery at admission.
• Allergy to penicillin, erythromycin, or azithromycin.
• Multiple gestations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Erythromycin; Erythromycin 250 mg IV every 6 hours for 48 hours, followed by 250 mg PO or 333 mg PO every 8 hours for 5 days	Drug: Erythromycin; Erythromycin 250 mg IV every 6 hours for 48 hours, followed by 250 mg PO or 333 mg PO every 8 hours for 5 days in addition to Ampicillin 2 gm IV every 6 hours for 2 days followed by Amoxicillin 250 mg PO every 8 hours for 5 days
Active Comparator: Azithromycin; Azithromycin 1 gm PO once or 500 mg PO followed by 250 mg PO daily for a total of 5 days	Drug: Azithromycin; Azithromycin 1 gm PO once or 500 mg PO followed by 250 mg PO daily for a total of 5 days in addition to Ampicillin 2 gm IV every 6 hours for 2 days followed by Amoxicillin 250 mg PO every 8 hours for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Latency period	Time from PPROM to delivery between the two treatments	Number of days from PPROM to delivery, assessed up to 105 days

Collaborators and Investigators

• Sponsor: Inova Health Care Services
• Collaborators: Eastern Virginia Medical School
• Investigators: Principal Investigator: Antonio Saad, MD, MBA, Inova Health Care Services

Publications and helpful links

General Publications

• Drassinower D, Friedman AM, Obican SG, Levin H, Gyamfi-Bannerman C. Prolonged latency of preterm prelabour rupture of membranes and neurodevelopmental outcomes: a secondary analysis. BJOG. 2016 Sep;123(10):1629-35. doi: 10.1111/1471-0528.14133. Epub 2016 May 31.
• Prelabor Rupture of Membranes: ACOG Practice Bulletin, Number 217. Obstet Gynecol. 2020 Mar;135(3):e80-e97. doi: 10.1097/AOG.0000000000003700.
• Navathe R, Schoen CN, Heidari P, Bachilova S, Ward A, Tepper J, Visintainer P, Hoffman MK, Smith S, Berghella V, Roman A. Azithromycin vs erythromycin for the management of preterm premature rupture of membranes. Am J Obstet Gynecol. 2019 Aug;221(2):144.e1-144.e8. doi: 10.1016/j.ajog.2019.03.009. Epub 2019 Mar 20.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: February 14, 2024
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 23, 2024

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: pprom; latency antibiotics; prom
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor Complications; Pregnancy Complications; Fetal Membranes, Premature Rupture; Preterm Premature Rupture of the Membranes; Organic Chemicals; Macrolides; Lactones; Polyketides; Azithromycin; Erythromycin
• Other Study ID Numbers: INOVA-2023-58; 23-08-WC-0198 (Other Identifier: Eastern Virginia Medical School)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes