Improvement of PPROM Management With Prophylactic Antimicrobial Therapy (iPROMPT)

NCT ID: NCT06396078

Last Updated: 2026-01-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-18
• Study Completion Date: 2026-12-31

Brief Summary

To conduct an unblinded pragmatic randomized controlled trial (pRCT) "Improvement of PPROM Management with Prophylactic Antimicrobial Therapy (iPROMPT)" of a seven-day course of ceftriaxone, clarithromycin, and metronidazole versus the current standard of care of a seven-day course of ampicillin/amoxicillin and azithromycin or erythromycin to prolong pregnancy and decrease adverse perinatal outcomes among hospitalized pregnant individuals undergoing expectant management of PPROM <34 weeks.

Detailed Description

Preterm prelabor rupture of membranes (PPROM) is the most common identifiable risk factor associated with preterm birth and affects 1 in 3 pregnant individuals in the United States with spontaneous preterm birth. Individuals diagnosed with PPROM who meet criteria for expectant management are currently admitted to the hospital for observation until delivery, which is generally recommended at 34 weeks' gestation unless indicated sooner. Initially upon admission, a course of prophylactic antibiotics is administered as this has been shown to prolong pregnancy and improve neonatal outcomes. The standard antibiotic regimen, primarily based on data published in 1997, includes ampicillin followed by amoxicillin with erythromycin or azithromycin for a total of 7 days. Ongoing studies are needed to determine the optimal prophylactic antibiotic regimen given changes in bacterial sensitivities over time, lack of adequate coverage for common organisms including genital mycoplasma, inadequate placental transfer of currently used antibiotic agents, ineffective antibiotic response at reducing the fetal inflammatory response, and new promising antibiotic agents that address these limitations. A promising expanded-spectrum alternative regimen with proof-of-concept is ceftriaxone, clarithromycin, and metronidazole. Observational studies have shown successful eradication of intraamniotic inflammation/infection using this new regimen. This regimen offers multiple potential advantages, including: higher bioavailability, higher transplacental transfer, and effectiveness against genital mycoplasma (clarithromycin), greater anaerobic coverage (metronidazole), and a longer half-life and expanded coverage against gram-negative bacteria (ceftriaxone) compared with the current standard regimen.

Conditions

Preterm Premature Rupture of Membrane; Pregnancy, High Risk; Preterm Birth

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention group

Participants randomized to the intervention group will receive the following regimen:

• Ceftriaxone 1 g IV q 24 hours x 7 days
• Clarithromycin 500 mg PO BID x 7 days
• Metronidazole 500 mg PO q 12 hours x 7 days

Group Type: EXPERIMENTAL

Ceftriaxone 1000 MG

Intervention Type: DRUG

Ceftriaxone 1 g IV q 24 hours x 7 days (in addition to clarithromycin and metronidazole)

Clarithromycin 500mg

Intervention Type: DRUG

Clarithromycin 500 mg PO BID x 7 days (in addition to ceftriaxone and metronidazole)

Metronidazole 500 mg

Intervention Type: DRUG

Metronidazole 500 mg PO q 12 hours x 7 days (in addition to clarithromycin and ceftriaxone)

Standard of care

Participants randomized to the standard care group will receive the following regimen:

• Ampicillin 2 g IV q 6 hours x 48 hours followed by amoxicillin 250 mg q 8 hours for an additional 5 days
• Azithromycin 1 g PO x 1 dose OR erythromycin 250 mg IV q 6 hours x 48 hours followed by erythromycin 333 mg PO TID for an additional 5 days

Group Type: OTHER

Ampicillin 2 GM Injection

Intervention Type: DRUG

Ampicillin 2 g IV q 6 hours x 48 hours (prior to amoxicillin and in addition to either azithromycin or erythromycin)

Amoxicillin 250 MG

Intervention Type: DRUG

Amoxicillin 250 mg q 8 hours for an additional 5 days (following ampicillin and in addition to either azithromycin or erythromycin)

Azithromycin

Intervention Type: DRUG

Azithromycin 1 g PO x 1 dose (in addition to ampicillin and amoxicillin)

Erythromycin

Intervention Type: DRUG

Erythromycin 250 mg IV q 6 hours x 48 hours followed by erythromycin 333 mg PO TID for an additional 5 days (in addition to ampicillin and amoxicillin)

Interventions

Ceftriaxone 1000 MG

Ceftriaxone 1 g IV q 24 hours x 7 days (in addition to clarithromycin and metronidazole)

Intervention Type: DRUG

Clarithromycin 500mg

Clarithromycin 500 mg PO BID x 7 days (in addition to ceftriaxone and metronidazole)

Intervention Type: DRUG

Metronidazole 500 mg

Metronidazole 500 mg PO q 12 hours x 7 days (in addition to clarithromycin and ceftriaxone)

Intervention Type: DRUG

Ampicillin 2 GM Injection

Ampicillin 2 g IV q 6 hours x 48 hours (prior to amoxicillin and in addition to either azithromycin or erythromycin)

Intervention Type: DRUG

Amoxicillin 250 MG

Amoxicillin 250 mg q 8 hours for an additional 5 days (following ampicillin and in addition to either azithromycin or erythromycin)

Intervention Type: DRUG

Azithromycin

Azithromycin 1 g PO x 1 dose (in addition to ampicillin and amoxicillin)

Intervention Type: DRUG

Erythromycin

Erythromycin 250 mg IV q 6 hours x 48 hours followed by erythromycin 333 mg PO TID for an additional 5 days (in addition to ampicillin and amoxicillin)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Admitted to the inpatient unit for expectant management of PPROM until delivery
• Age ≥ 18 years with the ability to provide informed consent
• Gestational age between 23 0/7 and 32 6/7 weeks

Exclusion Criteria

• Having received more than one dose of any prophylactic antibiotic
• Suspected or confirmed infection requiring treatment with antibiotics
• Allergy or contraindication to an antibiotic in either arm
• Maternal immunosuppression

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

Sponsors

Ohio State University

OTHER

Sponsor Role: lead

Responsible Party

Kartik K Venkatesh

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marissa Berry, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Kartik K Venkatesh, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine

Columbus, Ohio, United States

Site Status: RECRUITING

University of Texas Medical Branch

Galveston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Marissa Berry, MD

Role: CONTACT

Marissa.Berry@osumc.edu

614-293-4780

Facility Contacts

Marissa Berry, MD

Role: primary

Marissa.Berry@osumc.edu

614-293-4780

Benjamin Spires, MD

Role: primary

bpspires@UTMB.EDU

409-772-1193

Luis D Pacheco, MD

Role: backup

ldpachec@utmb.edu

Other Identifiers

2024H0122

Identifier Type: -

Identifier Source: org_study_id