Azithromycin Prophylaxis for PRElabor CEsarean DElivery Trial
- Conditions
- Obstetrical ComplicationsLabor and Delivery ComplicationCesarean Delivery
- Interventions
- Registration Number
- NCT06605118
- Lead Sponsor
- The George Washington University Biostatistics Center
- Brief Summary
This is a phase-III multi-center double-blind randomized controlled trial of 8,000 individuals undergoing a scheduled or prelabor cesarean delivery who are randomized to either adjunctive azithromycin prophylaxis or to placebo. Both groups also will receive standard of care preoperative antibiotics (excluding azithromycin). The primary endpoint is a maternal infection composite defined as any one of the following up to 6 weeks postpartum: endometritis, wound infection, abscess, septic thrombosis, sepsis, pneumonia, pyelonephritis and breast infection.
- Detailed Description
This is a phase-III multi-center double-blind randomized controlled trial of 8,000 individuals undergoing a scheduled or prelabor cesarean delivery who are randomized to either azithromycin prophylaxis or to placebo. All participants will receive standard of care preoperative antibiotics. The primary objective is to evaluate in patients undergoing scheduled/prelabor cesarean if pre-incision adjunctive azithromycin prophylaxis reduces the risk of post-cesarean infections compared with placebo. Secondary objectives include 1) to assess the perinatal and maternal safety of pre-incision adjunctive azithromycin, 2) to evaluate whether adjunctive azithromycin prophylaxis reduces maternal and neonatal resource use outcomes compared with placebo, and 3) to evaluate whether adjunctive azithromycin influences maternal and neonatal infection with resistant organisms compared with placebo.
Individuals will be randomized prior to the start of the cesarean to either 500mg of intravenous azithromycin or to placebo (normal saline). Maternal blood and cord blood will be collected on a subset of the population. Research staff will abstract maternal and neonatal outcomes following delivery and discharge from the hospital. A single maternal follow-up study visit at 6 weeks (4-8 weeks) postpartum will be scheduled to ascertain maternal and neonatal outcomes.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 8000
- ≥ 23 weeks' gestation (ACOG dating criteria)
- Scheduled or prelabor cesarean delivery
- Singleton or twin gestation
- Allergy or contraindication to azithromycin or macrolide antibiotics, including those with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of azithromycin
- Chorioamnionitis
- Bacterial infection (e.g., pyelonephritis) requiring ongoing antibiotic treatment after delivery
- Premature rupture of membranes (PROM) or labor (i.e., contractions with ongoing cervical change)
- Fetal demise or known major congenital anomaly
- Azithromycin treatment within 7 days
- Planned use of antimicrobial prophylaxis after delivery for any reason
- Known structural heart disease or active cardiomyopathy (current ejection fraction<40%)
- Known arrhythmia with QT prolongation or taking scheduled medications known to prolong the QT interval such that it would preclude the use of azithromycin
- Refusal or unable to obtain consent (e.g., language barrier)
- Participating in another intervention study that influences the primary outcome in this study
- Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, do not have to be excluded.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo and standard of care preoperative antibiotics Placebo Normal saline administered up to 1 hour prior to cesarean incision (or as soon as feasible after incision) and infused over one hour in addition to standard of care preoperative antibiotics (excluding azithromycin) prior to incision. Azithromycin prophylaxis and standard of care preoperative antibiotics Azithromycin Injection 500mg of intravenous azithromycin administered up to 1 hour prior to cesarean incision (or as soon as feasible after incision) and infused over one hour per FDA infusion recommendations for azithromycin. Additionally patients will received standard of care preoperative antibiotics (excluding azithromycin) prior to incision. Azithromycin prophylaxis and standard of care preoperative antibiotics Standard of Care Preoperative antibiotics 500mg of intravenous azithromycin administered up to 1 hour prior to cesarean incision (or as soon as feasible after incision) and infused over one hour per FDA infusion recommendations for azithromycin. Additionally patients will received standard of care preoperative antibiotics (excluding azithromycin) prior to incision. Placebo and standard of care preoperative antibiotics Standard of Care Preoperative antibiotics Normal saline administered up to 1 hour prior to cesarean incision (or as soon as feasible after incision) and infused over one hour in addition to standard of care preoperative antibiotics (excluding azithromycin) prior to incision.
- Primary Outcome Measures
Name Time Method Maternal infection composite Delivery up to 6 weeks postpartum (a period of up to 6 weeks) a maternal infection composite defined as any one of the following: endometritis, wound infection, abdominal or pelvic abscess, septic pelvic thrombosis, sepsis, pneumonia, pyelonephritis and breast infection
- Secondary Outcome Measures
Name Time Method Non-infections wound complications Delivery up to 6 weeks postpartum (a period of up to 6 weeks) any of the following wound complications without diagnosis of a wound infection: seroma, wound breakdown, erythema and/or hematoma
Perinatal composite outcome hospital discharge, 6 weeks of birth, or death (whichever occurs first) Any of the following:
* Neonatal death occurring within 28 days of birth or prior to initial discharge from hospital
* Respiratory distress syndrome
* Necrotizing enterocolitis grade 2 or higher
* Periventricular leucomalacia
* Intraventricular hemorrhage grades 3 or 4
* Bronchopulmonary dysplasia grade 3 or higher
* Suspected sepsis
* Confirmed sepsis
* Cardiac resuscitation
* Severe neonatal drug reaction defined as anaphylaxis or any other reported severe event suspected to be due to azithromycin
* Hypertrophic pyloric stenosis defined as physician diagnosis supported by surgical intervention (pyloromyotomy) or pathology evaluation through 6 weeks from birth.Number of neonates with Allergic Reaction birth through hospital discharge, or 7 days from birth, whichever is earliest Neonatal allergic reaction (e.g., skin rash) through discharge or 7 days from birth, whichever is earliest, suspected to be due to study medication.
Number of Neonates with Gastrointestinal Symptoms birth through hospital discharge, or 7 days from birth, whichever is earliest vomiting, diarrhea, feeding difficulty through discharge or 7 days from birth, whichever is earliest
Number of Maternal Deaths From randomization through 6 weeks postpartum (a period of up to 6 weeks) Death
Maternal Resource Composite From hospital discharge following delivery through 6 weeks postpartum (a period of up to 6 weeks) * Hospital readmission
* Emergency room (ER) visit
* Unscheduled clinic visitsNeonatal Resource Composite From hospital discharge following delivery through 6 weeks postpartum (a period of up to 6 weeks) * Hospital readmission
* Emergency Room (ER) visitMaternal Hospital Length of Stay Hospital admission to hospital discharge (up to 42 days) Length of hospital stay in days
Rate of Neonatal ICU Admission Delivery to hospital discharge (up to 120 days) Number of neonates admitted to NICU
Number of Participants with Maternal Resistant Infection Randomization through 6 weeks postpartum (a period of up to 6 weeks) bacteria and resistance patterns from clinical cultures
Number of Neonates with Neonatal Resistant Infection From birth up to 6 weeks of age bacteria and resistance patterns from clinical cultures
Trial Locations
- Locations (14)
University of Alabama - Birmingham
🇺🇸Birmingham, Alabama, United States
Regents of the University of California San Francisco
🇺🇸San Francisco, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Columbia University
🇺🇸New York, New York, United States
University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Duke University
🇺🇸Durham, North Carolina, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Magee Women's Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Brown Univeristy
🇺🇸Providence, Rhode Island, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Texas - Houston
🇺🇸Houston, Texas, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States