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NCT Number: NCT06396078

Improvement of PPROM Management With Prophylactic Antimicrobial Therapy (iPROMPT)

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.

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Key information

Conditions

Preterm Premature Rupture of Membrane Chorioamnionitis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Female Urogenital Diseases and Pregnancy Complications Fetal Diseases Fetal Membranes, Premature Rupture Obstetric Labor Complications Obstetric Labor, Premature Placenta Diseases Pregnancy Complications Pregnancy, High Risk Premature Birth Preterm Birth Preterm Premature Rupture of the Membranes Urogenital Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine, Columbus, Ohio, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ceftriaxone 1000 MG

Drug

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

Clarithromycin 500mg

Drug

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

Metronidazole 500 mg

Drug

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

Ampicillin 2 GM Injection

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

Drug

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

Azithromycin

Drug

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

Erythromycin

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)

Primary outcomes

  1. Latency

    Time frame: From randomization to delivery

    Latency will be measured in hours, and also reported as days for clinical interpretability.

Secondary outcomes

  1. Neonatal outcome composite checklist

    Time frame: From birth to up to 6 weeks postpartum

    Includes neonatal sepsis, respiratory distress syndrome, any mechanical ventilation, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, stillbirth, or neonatal death

  2. Endometritis

    Time frame: From birth to up to 6 weeks postpartum

    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)

  3. Surgical site infection

    Time frame: From birth to up to 6 weeks postpartum

    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.

  4. Individual clinical infections

    Time frame: From birth to up to 6 weeks postpartum

  5. Puerperal fever

    Time frame: From birth to up to 6 weeks postpartum

    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.

  6. Histopathologic chorioamnionitis/funisitis on histologic placental evaluation

    Time frame: From randomization to delivery

  7. Antibiotic receipt postpartum

    Time frame: From birth to up to 6 weeks postpartum

  8. Adverse events

    Time frame: From randomization to delivery

    Allergic reactions (anaphylaxis, angioedema, urticaria), Stevens Johnsons syndrome, gastrointestinal side effects (nausea, vomiting, constipation, diarrhea, ileus)

Study contacts

Contact information is provided by the study sponsor or research team.

Marissa Berry, MD

CONTACT

[email protected]

614-293-4780

Sponsors and collaborators

Lead sponsor

Ohio State University

Other

Registry information

Official study title

Improvement of PPROM Management With Prophylactic Antimicrobial Therapy

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
May 2, 2024
Registry last updated
Jan 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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