Azithromycin Dose and PPROM Treatment: a Pilot Randomized Controlled Trial

Phase 4

Completed

• Conditions: Preterm Premature Rupture of Membrane
• Interventions: Drug: Azithromycin Oral Product; Drug: Azithromycin 500 mg

• Registration Number: NCT04294069
• Lead Sponsor: Thomas Jefferson University

Brief Summary

This is a pilot randomized controlled trial to assess the pharmacokinetics and pharmacodynamics of azithromycin in pregnant singletons admitted with preterm premature rupture of membranes (PPROM) at 24 0/7- 33 0/7. Participants will be randomized 1:1 to either 1000mg azithromycin orally once or 500mg azithromycin orally daily for seven days in addition to standard care.

Detailed Description

This is a pilot randomized controlled trial to assess the pharmacokinetics and pharmacodynamics of azithromycin in pregnant singletons admitted with preterm premature rupture of membranes (PPROM) at 24 0/7- 33 0/7. Participants will be randomized 1:1 to either 1000mg azithromycin orally once or 500mg azithromycin orally daily for seven days in addition to standard care. During the course of eight days participants will have serial collection of amniotic fluid, maternal serum; and at delivery, of placenta, membrane, and cord blood. After delivery, neonatal respiratory samples will be collected as well.

Study Timeline

• Study First Submitted: 2020-02-18
• Study First Submitted QC: 2020-03-02
• Study First Posted: 2020-03-03
• Study Start: 2020-09-14
• Primary Completion: 2020-12-27
• Study Completion: 2021-04-01
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-24
• Last Update Posted: 2023-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 6

Inclusion Criteria

• Singleton gestation 24 0/7 -33 0/7 weeks'

• Diagnosed with preterm premature rupture of membranes:

  • History consistent with ruptured membranes (ie leaking, gush of fluid)
  • Sterile speculum exam with pooling
  • Fluid positive for ferning and/or nitrazine
  • With or without confirmatory test such as Amnisure

Exclusion Criteria

• • Contraindication to azithromycin

  • Active labor, abruption, chorioamnionitis at enrollment
  • Other contraindication to expectant management of PPROM at enrollment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Azithromycin 1000mg	Azithromycin Oral Product	1000mg azithromycin PO once at admission
Azithromycin 500mg	Azithromycin 500 mg	500mg azithromycin PO daily for seven days

Primary Outcome Measures

Name	Time	Method
Azithromycin trough in amniotic fluid	8 days	Primary outcome is the mean difference in azithromycin trough (Cmin) in amniotic fluid between the two dosing regimens using nonparametric test

Secondary Outcome Measures

Name	Time	Method
Intra-amniotic infection	3 months (delivery)	Incidence of maternal intra-amniotic infection at delivery
Histologic chorioamnionitis	3 months (delivery)	incidence of histologic chorioamnionitis in placental pathology
IL-6 in amniotic fluid	8 days	Mean difference in IL-6 at delivery or 8 days (which ever is first)
Trend in amniotic fluid cytokines	8 days	TNF alpha, IL-1B, IL-6, IL-8 over 8 day period from admission
Latency to delivery	3 months	Number days from admission to delivey
ureaplasma colonization of membranes	3 months	Culture swab taken of membranes after delivery
IL-8 in cord blood	3 months (delivery)	Mean difference in IL-8 in cord blood
Respiratory ureaplasma colonization in neonate	3 months	Culture of nasopharyngeal swab within 48 hours of delivery in neonates

Trial Locations

Locations (1)

Thomas Jefferson University Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States