Clinical trial NCT06396078: Improvement of PPROM Management With Prophylactic Antimicrobial Therapy (iPROMPT)
Official title: Improvement of PPROM Management With Prophylactic Antimicrobial Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Preterm Premature Rupture of Membrane
Pregnancy, High Risk
Preterm Birth
Keywords: Pregnancy
Preterm premature rupture of membranes
Latency
Chorioamnionitis
Antibiotic prophylaxis
Lead sponsor: Ohio State University
Sponsor class: OTHER
First posted: 2024-05-02
Enrollment: 56
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Latency
timeFrame: From randomization to delivery
Secondary outcomes:
measure: Neonatal outcome composite checklist
timeFrame: From birth to up to 6 weeks postpartum
measure: Endometritis
timeFrame: From birth to up to 6 weeks postpartum
measure: Surgical site infection
timeFrame: From birth to up to 6 weeks postpartum
measure: Individual clinical infections
timeFrame: From birth to up to 6 weeks postpartum
measure: Puerperal fever
timeFrame: From birth to up to 6 weeks postpartum
measure: Histopathologic chorioamnionitis/funisitis on histologic placental evaluation
timeFrame: From randomization to delivery
measure: Antibiotic receipt postpartum
timeFrame: From birth to up to 6 weeks postpartum
measure: Adverse events
timeFrame: From randomization to delivery
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine
state: Ohio
Study officials:
affiliation: Ohio State University
name: Marissa Berry, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University
name: Kartik K Venkatesh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: