A Phase 4 interventional study of Azithromycin (Azithro) and Standard Azithromycin Dosing in Preterm Prelabor Rupture of Membranes and PPROM, sponsored by Alexa Henderson. Recruiting at 1 site in United States. Open to female participants. Per ClinicalTrials.gov, last updated 2026-09-04.
Sponsored by Alexa Henderson · Phase 4, Interventional, and Treatment
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:
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.
Exclusion Criteria:
A single dose of oral azithromycin 1 gram which is given at the time of presentation in addition to the standard intravenous ampicillin 2g q6h for 48 hours followed by oral amoxicillin 250 mg q8 hours for 5 days.
Drug: Standard Azithromycin Dosing
The standard antibiotic regimen will be given in addition to Azithromycin 500g every other day for 7 additional doses.
Drug: Azithromycin (Azithro) · Drug: Standard Azithromycin Dosing
Azithromycin 500 mg every other day for 7 additional doses will be given in addition to the standard antibiotic regimen.
Oral Azithromycin 1g once.
Recruitment Capability
Number of participants recruited per week/month
Time frame: From recruitment to enrollment, up to 3 days.
Participant Eligibility
Percentage of eligible participants who agree to participate, reasons for refusal or ineligibility
Time frame: From recruitment until enrollment, up to 3 days.
Retention and Dropout Rates
Percentage of patients who complete study and reasons for withdrawal from study.
Time frame: From recruitment to completion of the study, up to 4 months.
Intervention Delivery
Percentage of interventions delivered as intended
Time frame: From recruitment to completion of intervention, up to 15 days.
Participant Acceptability
Likert-scale survey evaluating the participant's perceived affective attitude, burden, ethicality, intervention coherence, confidence, opportunity costs, general acceptability, and side effects related to the study.
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
Data completeness measured as number of participants with complete data entry.
Time frame: From recruitment to completion of postpartum period, up to 6 months.
Resource Use and Cost
Total cost versus planned budget, time and staffing required.
Time frame: From recruitment to postpartum period, up to 6 months.
Incidence of Treatment-Related Adverse Events [Safety and Tolerability]
Adverse events associated with antibiotic usage, maternal and neonatal outcomes, bacterial resistance profiles. Assessed using previously validated Medication Side Effect survey.
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
Incidence of protocol deviation, indications for protocol deviation.
Time frame: From recruitment to completion of intervention, up to 15 days.
Time for Delivery
Amount of study team time needed for delivery.
Time frame: From recruitment to completion of postpartum period, up to 6 months.
Financial Resources
Amount of monetary resources needed for study delivery.
Time frame: From recruitment to postpartum period, up to 6 months.
Pregnancy Latency
Number of days participants remain pregnant after PPROM until delivery
Time frame: From time of PPROM diagnosis (D0) until day of delivery, up to 3 months.
Pregnancy Outcome
Intrauterine fetal demise, neonatal demise while in NICU, living infant to NICU discharge.
Time frame: From time of PPROM diagnosis (D0) until day of delivery, up to 3 months.
NICU Admission
Requirement for NICU admission.
Time frame: From day of delivery through neonatal discharge, up to 4 months.
Neonatal Ventilatory Support
Level of ventilatory support required for neonate (none, bubble CPAP, intubation).
Time frame: From day of delivery through neonatal discharge, up to 4 months.
Neonatal Sepsis
Rates of early-onset sepsis, late-onset sepsis (including culture positive sepsis and culture-negative, clinically suspected sepsis)
Time frame: From day of delivery through neonatal discharge, up to 4 months.
Neonatal Intraventricular Hemorrhage (IVH)
Grade of IVH if present.
Time frame: From day of delivery through neonatal discharge, up to 4 months.
Neonatal respiratory distress syndrome
Documented respiratory distress syndrome by neonatology providers.
Time frame: From day of delivery through neonatal discharge, up to 4 months.
Necrotizing enterocolitis
Rate of documented necrotizing enterocolitis by neonatology team.
Time frame: From day of delivery through neonatal discharge, up to 4 months.
Mode of delivery
Cesarean section, vaginal delivery, or operative delivery.
Time frame: From day of PPROM (D0) through day of delivery, up to 3 months.
Indication for delivery
Non-reassuring fetal status, labor, intra-uterine infection, placental abruption, cord prolapse.
Time frame: From day of PPROM (D0) through day of delivery, up to 3 months.
Maternal group B streptococcus status
Positive or negative group B streptococcus maternal rectovaginal culture.
Time frame: From day of PPROM (D0) through day of delivery, up to 3 months.
Maternal postpartum hemorrhage
Estimated blood loss greater than 1000mL after delivery.
Time frame: From day of PPROM (D0) through 6 weeks postpartum, up to 4 months.
Suspected intraamniotic infection
Defined as maternal temperature greater than 39 degrees Celsius OR maternal temperature between 38.0-38.9 degrees Celsius plus one or more additional clinical risk factors: maternal leukocytosis greater than 15,000/mm\^3, purulent cervical drainage, or fetal tachycardia.
Time frame: From day of PPROM (D0) through day of delivery, up to 3 months.
Confirmed intraamniotic infection
Positive amniotic fluid test result OR placental pathology demonstrating histologic evidence of infection or inflammation.
Time frame: From day of PPROM (D0) through delivery with postpartum placental pathology result, up to 3 months.
Maternal sepsis
Suspected sepsis documented by clinical provider in chart or culture proven sepsis.
Time frame: From day of PPROM (D0) through 6 weeks postpartum, up to 4 months.
Maternal placental abruption
Clinical evidence of placental abruption documented by OBGYN provider.
Time frame: From day of PPROM (D0) through day of delivery, up to 3 months.
Maternal ICU Admission
Required admission to adult ICU prior to or after delivery.
Time frame: From day of PPROM (D0) through 6 weeks postpartum, up to 4 months.
Maternal postpartum endomtritis
Documented clinical diagnosis of endometritis in participant chart.
Time frame: From day of delivery through 6 weeks postpartum.
Maternal retained products of conception
Clinical documentation of retained products of conception in participant chart.
Time frame: From day of delivery through 6 weeks postpartum.
Additional maternal surgical procedures
Requirement of additional surgical procedures following delivery (suction dilation and curettage, hysterectomy).
Time frame: From day of delivery through 6 weeks postpartum.
Maternal blood transfusion
Documented maternal blood transfusion following delivery.
Time frame: From day of PPROM (D0) through 6 weeks postpartum, up to 4 months.
Maternal antibiotic course completion
Number of participants in intervention arm who completed the extended antibiotic course.
Time frame: From day of PPROM (D0) through day of delivery, up to D14.
Additional maternal antibiotic administration
Maternal antibiotics administered for other indications after enrollment in the study.
Time frame: From day of PPROM (D0) through day of delivery, up to 3 months.
Maternal placental pathology
Maternal and fetal inflammation stage/grade as defined by the Amsterdam Criteria.
Time frame: From day of PPROM (D0) through delivery with postpartum placental pathology result, up to 3 months.
Plan to share: Yes — All IPD collected throughout the study will potentially be shared with future collaborating sites if the feasibility trial is expanded to a multi-center trial.
Supporting information: Study protocol, Sap, Icf, Csr, Analytic code
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Preterm Premature Rupture of the Membranes