What is the mechanism of action of this treatment?

The most common treatments for Premature Rupture of Membranes (PROM) include antibiotics such as azithromycin, a second-generation macrolide. Azithromycin works by inhibiting bacterial protein synthesis, which prevents bacterial growth and reduces the risk of intrauterine infections. This is crucial for PROM patients because infections can lead to severe complications, including preterm labor and neonatal morbidity. By effectively managing bacterial infections, these treatments help to prolong pregnancy and improve outcomes for both the mother and the fetus.

What side effects are associated with this type of intervention?

The most common treatments for Premature Rupture of Membranes (PROM) include antibiotics such as azithromycin and erythromycin. Azithromycin, a second-generation macrolide, is generally well-tolerated but can cause gastrointestinal upset, including nausea, vomiting, and diarrhea. Erythromycin, another macrolide, is also associated with gastrointestinal side effects and can be less well-tolerated over a prolonged course. Both antibiotics can potentially cause allergic reactions, though these are rare. Other side effects may include liver enzyme abnormalities and, in rare cases, cardiac arrhythmias due to QT prolongation.

What prior FDA approvals exist?

The FDA has approved the use of antibiotics such as erythromycin for the treatment of Premature Rupture of Membranes (PROM) to prolong pregnancy and reduce neonatal morbidity and mortality. Erythromycin, a macrolide antibiotic, is commonly used in combination with ampicillin for a 7-day regimen in cases of preterm premature rupture of membranes (PPROM). Due to gastrointestinal side effects and a national shortage of erythromycin, azithromycin, a second-generation macrolide, is being studied as an alternative. Azithromycin is favored for its once-daily dosing, lower cost, and reduced gastrointestinal upset.

What other types of research exist?

Promising novel alternatives to Azithromycin for treating Premature Rupture of Membranes (PPROM) patients include newer macrolides like RU29065 and RU29702, which have shown better activity against certain bacteria compared to erythromycin. Additionally, considering the safety and efficacy profiles, other classes of antibiotics such as cephalosporins (e.g., ceftriaxone) or beta-lactam/beta-lactamase inhibitor combinations (e.g., amoxicillin-clavulanate) may also be considered, but their use should be guided by susceptibility patterns and clinical judgment.

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Penicillin Antibiotic

Azithromycin vs. Erythromycin for Premature Rupture of Membranes (TREAT Trial)

Phase 3

Waitlist Available

Led By Antonio F Saad, MD

Research Sponsored by The University of Texas Medical Branch, Galveston

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Maternal age ≥ 18 years and <50 years

Pregnant women between the gestational age 23 6/7 and 32 6/7 weeks

Must not have

Significant liver disease defined as known cirrhosis or elevated transaminases of at least 3-fold upper limit of normal

Clinical chorioamnionitis or any other active bacterial infection (e.g. pyelonephritis, pneumonia, abscess) at time of randomization: because standard antibiotic therapy for these conditions may confound trial intervention

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 7 days

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is comparing two antibiotics, erythromycin and azithromycin, to see which one helps pregnant women with early membrane rupture stay pregnant longer. The study focuses on women in the later stages of pregnancy. The goal is to delay labor, giving babies more time to develop and reducing health risks. Azithromycin has been studied for its effectiveness in prolonging pregnancy and reducing infections in cases of early membrane rupture.

Who is the study for?

This trial is for pregnant women aged 18-50, between 23+6/7 and 32+6/7 weeks of gestation with a single baby and PPROM. They must have less than 5cm cervical dilation, plan to deliver at JSH, and not have heart failure, placental anomalies, fetal demise, cerclage in place or allergies to the antibiotics used.

What is being tested?

The study compares two antibiotic regimens for treating PPROM: azithromycin versus erythromycin combined with ampicillin. The goal is to see which treatment is more effective at prolonging pregnancy without causing significant side effects.

What are the potential side effects?

Erythromycin may cause gastrointestinal upset leading some patients to struggle with the full course. Azithromycin tends to be easier on the stomach and has fewer issues related to digestive discomfort.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am a woman aged 18 to 49.

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I am pregnant and between 24 to 33 weeks along.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have severe liver disease or my liver tests are three times higher than normal.

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I do not have an active bacterial infection like chorioamnionitis.

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I have a cervical stitch in place.

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I have heart failure with reduced ejection fraction.

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My kidney function is impaired, with creatinine over 2.0 mg/dl or I am on dialysis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 7 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~7 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 7 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proportion of Women Still Pregnant by Day 7

Secondary study objectives

Latency Defined as Interval From PPROM to Delivery.

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: AzithromycinExperimental Treatment3 Interventions

Ampicillin 2 gm IV every 6 hours followed by amoxicillin 500 mg PO every 8 hours with Azithromycin 1 gm PO once at randomization.

Group II: ErythromycinActive Control3 Interventions

Ampicillin 2 gm IV every 6 hours followed by amoxicillin 250 mg PO every 8 hours for 5 days with erythromycin 250 mg IV every 6 hours for 48 hours followed by 500 mg PO every 8 hours for 5 days.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ampicillin

2015

Completed Phase 3

~5220

Amoxicillin

2017

Completed Phase 4

~7780

Azithromycin

2018

Completed Phase 4

~274950

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Premature Rupture of Membranes (PROM) include antibiotics such as azithromycin, a second-generation macrolide. Azithromycin works by inhibiting bacterial protein synthesis, which prevents bacterial growth and reduces the risk of intrauterine infections. This is crucial for PROM patients because infections can lead to severe complications, including preterm labor and neonatal morbidity. By effectively managing bacterial infections, these treatments help to prolong pregnancy and improve outcomes for both the mother and the fetus.

A New, Potent, and Placenta-Permeable Macrolide Antibiotic, Solithromycin, for the Prevention and Treatment of Bacterial Infections in Pregnancy.