Improvement of PPROM Management With Prophylactic Antimicrobial Therapy (iPROMPT)

Improvement of PPROM Management With Prophylactic Antimicrobial Therapy

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.

Study Overview

• Status: Recruiting
• Conditions: Preterm Birth; Pregnancy, High Risk; Preterm Premature Rupture of Membrane
• Intervention / Treatment: Drug: Ceftriaxone 1000 MG; Drug: Clarithromycin 500mg; Drug: Metronidazole 500 mg; Drug: Ampicillin 2 GM Injection; Drug: Amoxicillin 250 MG; Drug: Azithromycin; Drug: Erythromycin

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.

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marissa Berry, MD; Phone Number: 614-293-4780; Email: Marissa.Berry@osumc.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine
      • Contact: Marissa Berry, MD; Phone Number: 614-293-4780; Email: Marissa.Berry@osumc.edu
  • Texas
    • Galveston, Texas, United States, 775555
      • Recruiting
      • University of Texas Medical Branch
      • Contact: Benjamin Spires, MD; Phone Number: 409-772-1193; Email: bpspires@UTMB.EDU
      • Contact: Luis D Pacheco, MD; Email: ldpachec@utmb.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Ceftriaxone 1000 MG; Ceftriaxone 1 g IV q 24 hours x 7 days (in addition to clarithromycin and metronidazole); Drug: Clarithromycin 500mg; Clarithromycin 500 mg PO BID x 7 days (in addition to ceftriaxone and metronidazole); Drug: Metronidazole 500 mg; Metronidazole 500 mg PO q 12 hours x 7 days (in addition to clarithromycin and ceftriaxone)
Other: 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	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); 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); Drug: Azithromycin; Azithromycin 1 g PO x 1 dose (in addition to ampicillin and amoxicillin); 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Latency	Latency will be measured in hours, and also reported as days for clinical interpretability.	From randomization to delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal outcome composite checklist	Includes neonatal sepsis, respiratory distress syndrome, any mechanical ventilation, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, stillbirth, or neonatal death	From birth to up to 6 weeks postpartum
Endometritis	Diagnosed If the patient develops two of the following 1) oral body temperature ≥101°F at any time, or a temperature of ≥100.4 °F 24 hours after delivery, 2) maternal tachycardia that parallels the temperature, 3) uterine tenderness, 4) purulent vaginal discharge, or 5) associated findings with advanced endometritis (dynamic ileus, pelvic peritonitis, pelvic abscess, bowel obstruction, necrosis of the lower uterine segment)	From birth to up to 6 weeks postpartum
Surgical site infection	Presence of either superficial or deep incisional SSI described as cellulitis/erythema and induration around the incision or purulent discharge from the incision site, with or without fever, such as necrotizing fasciitis (diagnosed based on necrotizing wound infection). Intraabdominal abscess may or may not be present. Wound hematoma, seroma, or incisional breakdown alone in the absence of the above signs does not constitute infection.	From birth to up to 6 weeks postpartum
Individual clinical infections		From birth to up to 6 weeks postpartum
Puerperal fever	temperature ≥ 100.4 °F at least twice 30 minutes apart, or once with the use of antipyretic, or ≥ 101 °F once. This will be analyzed for intrapartum and postpartum fever.	From birth to up to 6 weeks postpartum
Histopathologic chorioamnionitis/funisitis on histologic placental evaluation		From randomization to delivery
Antibiotic receipt postpartum		From birth to up to 6 weeks postpartum
Adverse events	Allergic reactions (anaphylaxis, angioedema, urticaria), Stevens Johnsons syndrome, gastrointestinal side effects (nausea, vomiting, constipation, diarrhea, ileus)	From randomization to delivery

Collaborators and Investigators

• Sponsor: Ohio State University
• Investigators: Principal Investigator: Kartik K Venkatesh, MD, PhD, Ohio State University; Principal Investigator: Marissa Berry, MD, Ohio State University

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 25, 2024
• First Submitted That Met QC Criteria: May 1, 2024
• First Posted (Actual): May 2, 2024

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 23, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Chorioamnionitis; Pregnancy; Antibiotic prophylaxis; Latency; Preterm premature rupture of membranes
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Fetal Diseases; Placenta Diseases; Fetal Membranes, Premature Rupture; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Premature Birth; Chorioamnionitis; Preterm Premature Rupture of the Membranes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Imidazoles; Amides; Macrolides; Lactones; Penicillin G; beta-Lactams; Lactams; Cephalosporins; Thiazines; Nitroimidazoles; Nitro Compounds; Polyketides; Ampicillin; Penicillins; Cefotaxime; Cephacetrile; Ceftriaxone; Metronidazole; Amoxicillin; Clarithromycin; Azithromycin; Erythromycin
• Other Study ID Numbers: 2024H0122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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