PEACE: Erythromycin Versus Azithromycin in Preterm Premature Rupture of Membranes

Sponsor

Indiana University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01556334

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Preterm Premature Ruptured Membranes	Drug: Azithromycin Drug: Erythromycin	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Single (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)

Study Start Date :

Apr 1, 2010

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

Oct 1, 2012

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Time to delivery [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.