Improvement of PPROM Management With Prophylactic Antimicrobial Therapy (iPROMPT)

Preterm Birth Clinical Trial

Official title:

Improvement of PPROM Management With Prophylactic Antimicrobial Therapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06396078
• Other study ID #: 2024H0122
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: August 1, 2024
• Est. completion date: December 2025

Study information

• Verified date: May 2024
• Source: Ohio State University
• Contact: Marissa Berry, MD
• Phone: 614-293-4780
• Email: Marissa.Berry[@]osumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 56
• Est. completion date: December 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fetal Membranes, Premature Rupture
• Pregnancy, High Risk
• Premature Birth
• Preterm Birth
• Preterm Premature Rupture of Membrane
• Rupture

Intervention

Drug:
• Ceftriaxone 1000 MG
Ceftriaxone 1 g IV q 24 hours x 7 days (in addition to clarithromycin and metronidazole)
• Clarithromycin 500mg
Clarithromycin 500 mg PO BID x 7 days (in addition to ceftriaxone and metronidazole)
• Metronidazole 500 mg
Metronidazole 500 mg PO q 12 hours x 7 days (in addition to clarithromycin and ceftriaxone)
• 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)
• Amoxicillin 250 MG
Amoxicillin 250 mg q 8 hours for an additional 5 days (following ampicillin and in addition to either azithromycin or erythromycin)
• Azithromycin
Azithromycin 1 g PO x 1 dose (in addition to ampicillin and amoxicillin)
• 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)

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Latency	Latency will be measured in hours, and also reported as days for clinical interpretability.	From randomization to delivery
Secondary	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
Secondary	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
Secondary	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
Secondary	Individual clinical infections		From birth to up to 6 weeks postpartum
Secondary	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
Secondary	Histopathologic chorioamnionitis/funisitis on histologic placental evaluation		From randomization to delivery
Secondary	Antibiotic receipt postpartum		From birth to up to 6 weeks postpartum
Secondary	Adverse events	Allergic reactions (anaphylaxis, angioedema, urticaria), Stevens Johnsons syndrome, gastrointestinal side effects (nausea, vomiting, constipation, diarrhea, ileus)	From randomization to delivery