Extended Azithromycin Treatment in Prelabor Rupture of Membranes

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Recruitment Capability [Срок оценки: From recruitment to enrollment, up to 3 days.]
• Participant Eligibility [Срок оценки: From recruitment until enrollment, up to 3 days.]
• Retention and Dropout Rates [Срок оценки: From recruitment to completion of the study, up to 4 months.]
• Intervention Delivery [Срок оценки: From recruitment to completion of intervention, up to 15 days.]
• Participant Acceptability [Срок оценки: 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 [Срок оценки: From recruitment to completion of postpartum period, up to 6 months.]
• Resource Use and Cost [Срок оценки: From recruitment to postpartum period, up to 6 months.]
• Incidence of Treatment-Related Adverse Events [Safety and Tolerability] [Срок оценки: 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 [Срок оценки: From recruitment to completion of intervention, up to 15 days.]
• Time for Delivery [Срок оценки: From recruitment to completion of postpartum period, up to 6 months.]

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Pittsburgh Magee-Womens Hospital — Pittsburgh

Идентификаторы

NCT: NCT07669207 · STUDY25110085

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗