Erythromycin Versus Azithromycin in Preterm Premature Rupture of Membranes

NCT ID: NCT01556334

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2012-10-31

Brief Summary

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.

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.

Conditions

Preterm Premature Ruptured Membranes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Azithromycin

Azithromycin 1g po

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

Azithromycin 1g po

Erythromycin

Erythromycin IV followed by po for a total of 5 days.

Group Type: ACTIVE_COMPARATOR

Erythromycin

Intervention Type: DRUG

Erythromycin IV then PO

Interventions

Azithromycin

Azithromycin 1g po

Intervention Type: DRUG

Erythromycin

Erythromycin IV then PO

Intervention Type: DRUG

Other Intervention Names

amp/azithro; amp/erythro

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David M Haas, MD, MS

Role: PRINCIPAL_INVESTIGATOR

IU School of Medicine

Locations

Indiana University School of Medicine

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

PEACE Trial-1011004323

Identifier Type: -

Identifier Source: org_study_id