Clinical trial NCT06605118: Azithromycin Prophylaxis for PRElabor CEsarean DElivery Trial
Official title: Azithromycin Prophylaxis for Prelabor Cesarean Delivery Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Obstetrical Complications
Labor and Delivery Complication
Cesarean Delivery
Keywords: cesarean delivery
infection
maternal morbidity
antibiotics
prevention
Lead sponsor: The George Washington University Biostatistics Center
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: University of Alabama at Birmingham
First posted: 2024-09-20
Enrollment: 8000
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized shortly before delivery to receive either azithromycin administered intravenously or a placebo control of normal saline administered intravenously
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

* ≥ 23 weeks' gestation (ACOG dating criteria)
* Scheduled or prelabor cesarean delivery
* Singleton or twin gestation

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Maternal infection composite
timeFrame: Delivery up to 6 weeks postpartum (a period of up to 6 weeks)
Secondary outcomes:
measure: Non-infections wound complications
timeFrame: Delivery up to 6 weeks postpartum (a period of up to 6 weeks)
measure: Perinatal composite outcome
timeFrame: hospital discharge, 6 weeks of birth, or death (whichever occurs first)
measure: Number of neonates with Allergic Reaction
timeFrame: birth through hospital discharge, or 7 days from birth, whichever is earliest
measure: Number of Neonates with Gastrointestinal Symptoms
timeFrame: birth through hospital discharge, or 7 days from birth, whichever is earliest
measure: Number of Maternal Deaths
timeFrame: From randomization through 6 weeks postpartum (a period of up to 6 weeks)
measure: Maternal Resource Composite
timeFrame: From hospital discharge following delivery through 6 weeks postpartum (a period of up to 6 weeks)
measure: Neonatal Resource Composite
timeFrame: From hospital discharge following delivery through 6 weeks postpartum (a period of up to 6 weeks)
measure: Maternal Hospital Length of Stay
timeFrame: Hospital admission to hospital discharge (up to 42 days)
measure: Rate of Neonatal ICU Admission
timeFrame: Delivery to hospital discharge (up to 120 days)
measure: Number of Participants with Maternal Resistant Infection
timeFrame: Randomization through 6 weeks postpartum (a period of up to 6 weeks)
measure: Number of Neonates with Neonatal Resistant Infection
timeFrame: From birth up to 6 weeks of age
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: San Francisco
country: United States
facility: Regents of the University of California San Francisco
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: New York
country: United States
facility: Columbia University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee Women's Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Brown Univeristy
state: Rhode Island
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: University of Texas - Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Alabama at Birmingham
name: Alan T.N. Tita, MD PhD
role: STUDY_CHAIR
affiliation: University of North Carolina, Chapel Hill
name: Kim Boggess, MD
role: STUDY_CHAIR
affiliation: Eunice Kennedy Shriver NICHD
name: Monica Longo, MD PhD
role: STUDY_DIRECTOR
affiliation: The George Washington University Biostatistics Center
name: Rebecca G Clifton, PhD
role: PRINCIPAL_INVESTIGATOR
References: