NCT06396078

Improvement of PPROM Management With Prophylactic Antimicrobial Therapy (iPROMPT)

Improvement of PPROM Management With Prophylactic Antimicrobial Therapy

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 56 (estimated)
• Sponsor: Ohio State University · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
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)
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)

Timeline

• Start date: 2024-07-18
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2024-05-02
• Last updated: 2026-01-27

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study