Azithromycin Dose and PPROM Treatment: a Pilot Randomized Controlled Trial (ADAPT)

Azithromycin Pharmacokinetics and Pharmacodynamics in Pregnancy and Preterm Birth Prevention: Optimizing Dosing to Improve Maternal and Neonatal Outcomes

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.

Study Overview

• Status: Completed
• Conditions: Preterm Premature Rupture of Membrane
• Intervention / Treatment: Drug: Azithromycin 500 mg; Drug: Azithromycin Oral Product

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Azithromycin 500mg; 500mg azithromycin PO daily for seven days	Drug: Azithromycin 500 mg; 500mg azithromycin PO for seven days starting on admission
Active Comparator: Azithromycin 1000mg; 1000mg azithromycin PO once at admission	Drug: Azithromycin Oral Product; 1000mg azithromycin PO once at admission

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: Christiana Care Health Services
• Investigators: Principal Investigator: Rupsa C Boelig, MD, Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2020
• Primary Completion (Actual): December 27, 2020
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 3, 2020

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Rupture; Premature Birth; Fetal Membranes, Premature Rupture; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: 20G.119

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD available on request pending completion of data sharing agreement and approval of information requested
• IPD Sharing Time Frame: 1 year after publication of results
• IPD Sharing Access Criteria: IPD available on request pending completion of data sharing agreement and approval of information requested
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No