Improvement of PPROM Management With Prophylactic Antimicrobial Therapy (iPROMPT)

The Ohio State University

Status and phase: Enrolling; Phase 4

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

Treatments: Drug: Clarithromycin 500mg; Drug: Ceftriaxone 1000 MG; Drug: Amoxicillin 250 MG; Drug: Azithromycin; Drug: Metronidazole 500 mg; Drug: Ampicillin 2 GM Injection; Drug: Erythromycin

Study type: Interventional

Funder types: Other

Identifiers

NCT06396078

2024H0122

Details and patient eligibility

About

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.

Full 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.

Enrollment: 56 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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56 participants in 2 patient groups

Intervention group

Experimental group

Description:

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

Treatment:

Drug: Metronidazole 500 mg

Drug: Ceftriaxone 1000 MG

Drug: Clarithromycin 500mg

Standard of care

Other group

Description:

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

Treatment:

Drug: Erythromycin

Drug: Ampicillin 2 GM Injection

Drug: Azithromycin

Drug: Amoxicillin 250 MG