Erythromycin Versus Azithromycin in Preterm Premature Rupture of Membranes (PEACE)

October 11, 2024 updated by: Indiana University

Preterm Premature Rupture of Membranes: Erythromycin Versus Azithromycin a Randomized Trial Comparing Their Efficacy to Prolong Latency (PEACE Trial)

Preterm Premature Rupture of Membranes (PPROM) is treated with an antibiotic, erythromycin or azithromycin, to prolong pregnancy. Erythromycin is taken for several days and can result in stomach upset in some patients, causing them to stop taking the medication. Therefore, azithromycin is often prescribed instead. Azithromycin is usually taken only once and stomach upset is not seen or greatly reduced. The goal of this study is to see if there is a difference between the antibiotic (azithromycin) compared to the antibiotic (erythromycin) in prolonging pregnancy in patients with Preterm Premature Rupture of Membranes (PPROM). The working hypothesis is that there is no difference in the clinical effectiveness between antibiotic regimens containing the macrolides azithromycin and erythromycin for prolonging latency in PPROM.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Preterm, premature rupture of membranes complicates 140,000 pregnancies annually in the United States and is a major contributor to pre-term births and resultant neonatal morbidity and mortality. Typically, a brief period of latency exists after PPROM, with 70-80% of women delivering within the 1st week of membrane rupture. It has been shown through numerous well-conducted trials that antibiotics can prolong this latency time to delivery. Mercer and et al., demonstrated that the administration of ampicillin with erythromycin prolonged the median time to delivery, in comparison to placebo, from 2.9 to 6.1 days. This regimen has now become the standard protocol of treatment in PPROM patients. However, this protocol requires a multi-day dosing regimen of erythromycin and it has been known to have untoward gastrointestinal side effects leading to decreased patient compliance. To overcome these challenges, azithromycin, a newer 2nd generation macrolide, is now commonly being used as a substitution on many of our labor and delivery units nationwide. Azithromycin has a long intracellular half-life, which allows for a more patient friendly one-time dosing regimen; in addition many of the unwanted side effects seen with erythromycin are not seen or greatly reduced with azithromycin, making it an attractive alternative. Despite its popular use, there is a lack of evidence in the literature to support azithromycin as an agent to prolong latency. The purpose of this study is to demonstrate that there is no difference in the clinical effectiveness of azithromycin and erythromycin for prolonging latency in PPROM patients. This trial will be a prospective randomized trial performed in singleton pregnancies with PPROM between 24 0/7 - 32 0/7 weeks gestation. The protocol will enroll 250 eligible women who will then be randomized to receive either azithromycin 1 gm orally at enrollment or erythromycin 250mg IV every 6 hours for 48 hours followed by 500mg orally every 8hours for 5 days. All women will also receive the standard ampicillin 2gm IV every 6 hours followed by amoxicillin 250mg orally every 8 hours for 5 days. The primary outcome measure is the time of latency between the two groups. Secondary outcomes of neonatal death, need for oxygen supplementation, ventilation, and neonatal infection, will also be reviewed. In addition, side effect profiles between the two will be assessed in a post treatment patient survey.

Study Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pregnant women at least 18 years old
  • Gestational age of 24 0/7 to 32 0/7 weeks
  • Singleton gestation
  • Randomization within 36 hours of rupture of membranes.
  • Cervical dilation less than or equal to 4 cm.

Exclusion Criteria:

  • Known lethal fetal anomaly
  • Vaginal bleeding not associated with labor
  • Maternal or fetal indication for delivery
  • Diagnosis of chorioamnionitis on admission
  • Cervical cerclage in place
  • Placenta previa or other known placental anomalies
  • Use of antibiotic therapy within 5 days.
  • Allergy or other contraindications to erythromycin/azithromycin or steroid use.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Azithromycin
Azithromycin 1g po
Drug: Azithromycin
Azithromycin 1g po
Other Names:
  • amp/azithro
Active Comparator: Erythromycin
Erythromycin IV followed by po for a total of 5 days.
Drug: Erythromycin
Erythromycin IV then PO
Other Names:
  • amp/erythro

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to delivery
Time Frame: 2 years
To compare the mean time to delivery, using azithromycin versus erythromycin to prolong latency in PPROM patients. The working hypothesis for this aim is that there is no difference in the clinical effectiveness between antibiotic regimens containing the macrolides azithromycin and erythromycin for prolonging latency in PPROM.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indiana University

Investigators

  • Principal Investigator: David M Haas, MD, MS, IU School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Actual)

October 1, 2012

Study Completion (Actual)

October 1, 2012

Study Registration Dates

First Submitted

March 14, 2012

First Submitted That Met QC Criteria

March 15, 2012

First Posted (Estimated)

March 16, 2012

Study Record Updates

Last Update Posted (Actual)

October 15, 2024

Last Update Submitted That Met QC Criteria

October 11, 2024

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PEACE Trial-1011004323

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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