Azithromycin Versus Erythromycin For Preterm Prelabor Rupture of Membranes

Study Overview
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Brief Summary
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Aim 1. To examine the latency period according to antibiotic regimens (erythromycin iv for two days followed by orally for 5 days vs. azithromycin iv for 2 days followed by 5 days orally). Aim 2. To examine the latency period according to races stratified by antibiotic regimens. Aim 3: To examine if there is a difference in neonatal morbidity and mortality stratified by antibiotic regimen.

Detailed Description
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Significant differences exist in the pharmacokinetics and pharmacodynamics pathways of macrolide antibiotics between different races and ethnicities. Erythromycin compared to azithromycin interacts with more proteins and is likely affected by genetic variation. Therefore, the investigators hypothesize that the optimal latency antibiotic regimens for PPROM could potentially differ between races. Due to the paucity of data regarding the use of an azithromycin regimen for latency antibiotics, the Eastern Virginia Medical School MFM team uses an erythromycin regimen even though azithromycin requires less frequent dosing, has lower rates of side effects, and is more cost effective. The Center for Maternal and Child Health Equity at Eastern Virginia Medical School was developed to address health disparities for mothers and their children, and the investigator team is committed to working with the center to address this research gap regarding latency antibiotic use in PPROM. The aim is to determine the optimal antibiotic regimen for women with PPROM. The hypothesis to be tested are 1) The antibiotic regimen with azithromycin (iv for 2 days followed by 5 days orally) is associated with a longer latency period compared to the antibiotic regimen with erythromycin, and 2) The antibiotic regimen with azithromycin reduces disparity in latency period compared to the antibiotic regimen with erythromycin.

Official Title
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Azithromycin Versus Erythromycin For Preterm Prelabor Rupture of Membranes: A Randomized Controlled Trial

Conditions
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Preterm Premature Rupture of Membrane

Intervention / Treatment
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* Drug: Antibiotics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Singleton pregnancy PPROM from 22 weeks 0 days to 31 weeks 6 days at Sentara Norfolk General Hospital Membrane rupture within 36 hours of randomization, cervical dilation 3 cm or less, and 4 or fewer contractions in the 60-minutes monitoring before randomization Exclusion Criteria: Non-reassuring fetal heart tracing Vaginal bleeding Indications for delivery Received any antibiotic therapy within 7 days other than initiation of Ampicillin treatment as part of latency antibiotics prior to transfer to Sentara Norfolk General Hospital Allergy to penicillin, erythromycin, or azithromycin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: In order to maintain balanced groups, block randomization will be used. Pregnant women will be randomized in blocks of 6 with a total number of blocks to be 40. This will be conducted using STATA16 software, which will generate random permutations of sequential IDs of eligible study participants and their assignment to the treatment arms. This will be transferred to the REDCap in which a database will be created to facilitate random assignment during recruitment while maintaining concealment of randomization.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erythromycin<br>Receive 1) erythromycin 250 mg iv every 6 hours for 48 hours followed by 333 mg orally (pills) every 8 hours for 5 days | Drug: Antibiotics<br>* In the absence of labor, broad-spectrum antibiotics (often called latency antibiotics) are recommended for women with PPROM less than 34 weeks to reduce chorioamnionitis, prolong latency, and decrease neonatal sepsis (12,13).<br>* Other names: Broad-spectrum antibiotics;|
| Experimental: Azithromycin<br>Receive azithromycin 500 mg iv daily for 48 hours followed by 500 mg orally (pills) for 5 days. | Drug: Antibiotics<br>* In the absence of labor, broad-spectrum antibiotics (often called latency antibiotics) are recommended for women with PPROM less than 34 weeks to reduce chorioamnionitis, prolong latency, and decrease neonatal sepsis (12,13).<br>* Other names: Broad-spectrum antibiotics;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Latency Period | The time interval between the first antibiotic dose to time of delivery. | At delivery |