Extended Azithromycin Treatment in Prelabor Rupture of Membranes

Official title

Extended Azithromycin Treatment in Peri-viable and Extremely Preterm Prelabor Rupture of Membranes: A Pilot Study

Overview

The purpose of this study is to learn whether adding extra doses of azithromycin to the standard antibiotic treatment for preterm prelabor rupture of membranes may improve pregnancy outcomes for patients between 22 weeks and 28 weeks gestational age. Researchers will compare the standard antibiotic treatment to the standard antibiotic treatment with additional doses of azithromycin. Participants will: * Be randomly assigned to one of two groups: * The standard antibiotic treatment * The standard antibiotic treatment plus 7 additional doses of oral azithromycin 500 mg every other day. * Participants will be asked to complete a survey regarding their experience and side effects.

Detailed description

Multiple randomized trials have shown that antibiotic treatment for preterm prelabor rupture of membranes (PPROM) increases pregnancy latency and decreases maternal and neonatal morbidity. However, the optimal dosing schedule for azithromycin in PPROM is not fully understood. This pilot study will assess the feasibility of a non-blinded, randomized-controlled trial comparing maternal and neonatal outcomes between the standard PPROM antibiotic regimen and the standard regimen with extended azithromycin therapy in participants with periviable and extremely preterm PPROM between 22- and 28-weeks gestational age. Preliminary data on pregnancy latency, maternal morbidity, and neonatal outcomes will also be collected. Findings from this feasibility study will inform the design of a future, powered study.

The investigators hypothesize that extended azithromycin therapy may be associated with longer pregnancy latency and decreased rates of maternal and neonatal morbidity compared to standard therapy. This hypothesis is exploratory, and the present feasibility study is not powered to test a hypothesis.

The primary objective is to evaluate the feasibility of conducting a non-blinded, randomized controlled trial of extended azithromycin therapy in participants with periviable and extremely preterm prelabor rupture of membranes (PPROM) who desire expectant management between 22 and 28 weeks gestational age. Specifically, we aim to assess feasibility metrics including recruitment and consent rates, randomization procedures, adherence to the study protocol, and completeness of follow-up.

The secondary objectives of this pilot study are to estimate the variability (standard deviation) of pregnancy latency in this population to inform sample-size calculations for a future definitive trial. The investigators will also collect preliminary data on maternal outcomes (e.g., rates of intra-amniotic infection, endometritis, and placental abruption) and neonatal outcomes (gestational age at delivery, NICU admission, morbidity) for planning purposes. Additionally, the investigators will review placental pathology reports to identify the stage/grade of chorioamnionitis per the Amsterdam criteria. The investigators will obtain an initial estimate of the effect of extended azithromycin on pregnancy latency, recognizing that this pilot study is not powered to detect clinically meaningful differences.

Interventions

• Drug Azithromycin (Azithro)
  Azithromycin 500 mg every other day for 7 additional doses will be given in addition to the standard antibiotic regimen.
• Drug Standard Azithromycin Dosing
  Oral Azithromycin 1g once.

Primary outcome measures

• Recruitment Capability [Time frame: From recruitment to enrollment, up to 3 days.]
• Participant Eligibility [Time frame: From recruitment until enrollment, up to 3 days.]
• Retention and Dropout Rates [Time frame: From recruitment to completion of the study, up to 4 months.]
• Intervention Delivery [Time frame: From recruitment to completion of intervention, up to 15 days.]
• Participant Acceptability [Time frame: At completion of study (either after Day 14 of study or after delivery if does not complete study) prior to hospital discharge.]
• Data Collection Procedures [Time frame: From recruitment to completion of postpartum period, up to 6 months.]
• Resource Use and Cost [Time frame: From recruitment to postpartum period, up to 6 months.]
• Incidence of Treatment-Related Adverse Events [Safety and Tolerability] [Time frame: Ongoing during treatment from Day 2 through Day 14. Formally assessed with surveys as above on Day 8 and Day 14 (or earlier if delivers prior to completion of study period).]
• Protocol Deviations [Time frame: From recruitment to completion of intervention, up to 15 days.]
• Time for Delivery [Time frame: From recruitment to completion of postpartum period, up to 6 months.]

Secondary outcome measures (12)

• Pregnancy Latency [Time frame: From time of PPROM diagnosis (D0) until day of delivery, up to 3 months.]
• Pregnancy Outcome [Time frame: From time of PPROM diagnosis (D0) until day of delivery, up to 3 months.]
• NICU Admission [Time frame: From day of delivery through neonatal discharge, up to 4 months.]
• Neonatal Ventilatory Support [Time frame: From day of delivery through neonatal discharge, up to 4 months.]
• Neonatal Sepsis [Time frame: From day of delivery through neonatal discharge, up to 4 months.]
• Neonatal Intraventricular Hemorrhage (IVH) [Time frame: From day of delivery through neonatal discharge, up to 4 months.]
• Neonatal respiratory distress syndrome [Time frame: From day of delivery through neonatal discharge, up to 4 months.]
• Necrotizing enterocolitis [Time frame: From day of delivery through neonatal discharge, up to 4 months.]
• Mode of delivery [Time frame: From day of PPROM (D0) through day of delivery, up to 3 months.]
• Indication for delivery [Time frame: From day of PPROM (D0) through day of delivery, up to 3 months.]
• Maternal group B streptococcus status [Time frame: From day of PPROM (D0) through day of delivery, up to 3 months.]
• Maternal postpartum hemorrhage [Time frame: From day of PPROM (D0) through 6 weeks postpartum, up to 4 months.]

Eligibility criteria

Inclusion criteria

• Singleton gestation
• Gestational age at time of PPROM between 22w0d and 28w0d
• Opting for expectant management in the inpatient setting after completion of a maternal-fetal medicine and neonatology consultation (per standard of care)
• Remain pregnant 48 hours after presentation.
• Patients who receive betamethasone, magnesium therapy, and/or a limited course of tocolysis (through the betamethasone window) will be included.
• Pregnant patients below the age of 18 are eligible.

Exclusion criteria

• Contraindications to expectant management (clinical intra-amniotic infection, active preterm labor, or acute placental abruption)
• Lethal congenital defects
• Multiple gestation
• Ongoing alternative antibiotic treatment
• Known hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic
• History of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin
• Known prolongation of QT interval
• History of torsades de pointes
• Congenital long QT syndrome
• Bradyarrhythmia
• Decompensated heart failure
• Drugs known to significantly prolong the QT interval including Class 1A and Class III antiarrhythmic agents
• Impaired hepatic function
• GFR<10 mL/min
• Diagnosis of myasthenia gravis

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Pittsburgh Magee-Womens Hospital — Pittsburgh

Identifiers

NCT: NCT07669207 · STUDY25110085

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗