Azithromycin Dose and PPROM Treatment: a Pilot Randomized Controlled Trial

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Preterm Premature Rupture of Membrane

Intervention / Treatment
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* Drug: Azithromycin 500 mg
* Drug: Azithromycin Oral Product


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Azithromycin 500mg<br>500mg azithromycin PO daily for seven days | Drug: Azithromycin 500 mg<br>* 500mg azithromycin PO for seven days starting on admission<br>|
| Active Comparator: Azithromycin 1000mg<br>1000mg azithromycin PO once at admission | Drug: Azithromycin Oral Product<br>* 1000mg azithromycin PO once at admission<br>|

What is the study measuring?
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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) |