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

This study has been withdrawn prior to enrollment.
(Terminated before starting due to need for IND determined by FDA.)
Sponsor:
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT01556334
First received: March 14, 2012
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Preterm Premature Ruptured Membranes
Drug: Azithromycin
Drug: Erythromycin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Preterm Premature Rupture of Membranes: Erythromycin Versus Azithromycin a Randomized Trial Comparing Their Efficacy to Prolong Latency (PEACE Trial)

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Time to delivery [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 0
Study Start Date: April 2010
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azithromycin
Azithromycin 1g po
Drug: Azithromycin
Azithromycin 1g po
Other Name: amp/azithro
Active Comparator: Erythromycin
Erythromycin IV followed by po for a total of 5 days.
Drug: Erythromycin
Erythromycin IV then PO
Other Name: amp/erythro

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01556334

Locations
United States, Indiana
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
Investigators
Principal Investigator: David M Haas, MD, MS IU School of Medicine
  More Information

No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT01556334     History of Changes
Other Study ID Numbers: PEACE Trial-1011004323
Study First Received: March 14, 2012
Last Updated: March 4, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Indiana University:
premature ruptured membranes
azithromycin
erythromycin
latency
antibiotics

Additional relevant MeSH terms:
Fetal Membranes, Premature Rupture
Obstetric Labor Complications
Pregnancy Complications
Erythromycin
Erythromycin Estolate
Erythromycin Ethylsuccinate
Erythromycin stearate
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Synthesis Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014