Outpatient Antibiotics Following Previable Rupture of Membranes (pPPROM) Between 18 0/7 and 22 6/7 Weeks Gestational Age

April 16, 2025 updated by: David Hackney MD, MS, University Hospitals Cleveland Medical Center
A randomized, controlled, non-placebo trial to primarily assess the effect of oral, outpatient antibiotics (i.e., azithromycin and amoxicillin) on latency (i.e., proportion of patients that deliver within 28 days from membrane rupture) following previable, prelabor rupture of membranes between 18 0/7 and 22 6/7 weeks gestational age.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

88

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • English-speaking
  • Pregnant
  • Live, singleton gestation
  • Patient able to provide informed consent
  • Gestational age between 18 weeks and 0 days and 22 weeks and 6 days at the time of -membrane rupture
  • Diagnosis of preterm, prelabor rupture of membranes by clinical exam findings of either 1) visualization of amniotic fluid passing from the cervical canal and/or pooling in the vagina via sterile speculum examination, 2) a basic pH (i.e., positive nitrazine) test of vaginal fluid, 3) arborization (i.e., ferning) of dried vaginal fluid identified via microscopic examination, and/or 4) an amniotic fluid index (AFI) of less than 4cm

Exclusion Criteria:

  • Gestational dating performed or confirmed by ultrasound at ≥ 18 weeks and 0 days gestational age
  • Patient desires pregnancy interruption or induction of labor
  • Known major fetal anomaly or aneuploidy
  • Amniocentesis ≤ 7 days of diagnosis of rupture of membranes
  • Cervical cerclage placement ≤ 7 days of diagnosis of rupture of membranes
  • Known drug allergy or significant adverse reactions to macrolide or penicillin antibiotics
  • Current antibiotic use at the time of membrane rupture diagnosis
  • Vaginal bleeding at the time of membrane rupture diagnosis or within first 24 hours from diagnosis
  • Febrile at the time of membrane rupture diagnosis (i.e., temperature ≥ 38 degrees Celsius) and/or within first 24 hours of diagnosis
  • Active preterm labor at the time of membrane rupture diagnosis (i.e., consistent contraction pattern associated with cervical change) and/or within first 24 hours of diagnosis
  • Cervical dilation of ≥ 4 cm
  • Prolapse of fetal parts beyond the level of the internal cervical os
  • Declination to complete full, 7-day outpatient monitoring prior to hospital re-admission should rupture occur during the 22nd week of gestation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Antibiotics
Patients randomized into the treatment (i.e., antibiotics) arm of the study will be treated with a seven-day course of oral azithromycin and amoxicillin. Azithromycin will be dosed as single 500 mg dose (2-250mg oral tablets) administered immediately following randomization, yet prior to discharge to home, followed with 1-250mg oral tablet daily for 4 additional days (for a total of 5 days). Amoxicillin will be dosed as a single-500mg oral tablet three times daily for 7 days with first dose also being given prior to discharge home.
Drug: Azithromycin Pill
Azithromycin will be dosed as single 500 mg dose (2-250mg oral tablets) administered immediately following randomization, yet prior to discharge to home, followed with 1-250mg oral tablet daily for 4 additional days (for a total of 5 days).
Drug: Amoxicillin Pill
Amoxicillin will be dosed as a single-500mg oral tablet three times daily for 7 days with first dose also being given prior to discharge home.
No Intervention: No antibiotics
Patients randomized into the control (i.e., no antibiotics arm) will be managed according to standard of care practices for previable PPROM desiring of expectant management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Delivery within 28 days
Time Frame: 28 days from date of rupture
The proportion of patients that undergo a spontaneous or medically-indicated delivery within 28 days from diagnosis of previable prelabor rupture of membranes (pPPROM)
28 days from date of rupture

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severe maternal morbidity composite
Time Frame: From diagnosis of membrane rupture to 6 weeks following delivery
The proportion of patient's "positive" for severe maternal morbidity composite. A patient will be termed "positive" for severe maternal morbidity composite if any one of the following is diagnosed: maternal sepsis, postpartum hemorrhage, maternal ICU admission, maternal death.
From diagnosis of membrane rupture to 6 weeks following delivery
Severe neonatal morbidity composite
Time Frame: From date of delivery to date of hospital discharge (up to 6 months)
The proportion of patient's "positive" for severe neonatal morbidity composite. A neonate will be termed "positive" for severe neonatal morbidity composite if any one of the following is diagnosis: bronchopulmonary dysplasia (BPD), pulmonary hypoplasia, intraventricular hemorrhage (IVH) grade III/IV, necrotizing enterocolitis (NEC) Bell's Stage II or greater, neonatal sepsis with positive blood cultures, neonatal pneumonia with positive blood cultures, neonatal death.
From date of delivery to date of hospital discharge (up to 6 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospitals Cleveland Medical Center

Collaborators

The Cleveland Clinic
MetroHealth Medical Center

Investigators

  • Principal Investigator: David Hackney, MD, University Hospitals Cleveland Medical Center
  • Principal Investigator: Justin Lappen, MD, The Cleveland Clinic
  • Principal Investigator: Brian Mercer, MD, MetroHealth Hospitals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 13, 2023

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

April 14, 2022

First Submitted That Met QC Criteria

April 14, 2022

First Posted (Actual)

April 26, 2022

Study Record Updates

Last Update Posted (Actual)

April 22, 2025

Last Update Submitted That Met QC Criteria

April 16, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY20220251

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Once data collection and primary analysis has been completed. A de-identified data set will be provided.

IPD Sharing Time Frame

Data will become available upon publication of study results and remain available for 2 years upon study completion.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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