Azithromycin Prophylaxis for PRElabor CEsarean DElivery Trial (PRECEDE)

Azithromycin Prophylaxis for Prelabor Cesarean Delivery Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Obstetrical Complications; Cesarean Delivery; Labor and Delivery Complication
• Intervention / Treatment: Drug: Azithromycin Injection; Drug: Standard of Care Preoperative antibiotics; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 8000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Rebecca G Clifton, PhD; Phone Number: 301-881-9260; Email: rclifton@bsc.gwu.edu
• Study Contact Backup: Name: Steven Weiner, MS; Email: weiner@bsc.gwu.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama - Birmingham
      • Principal Investigator: Alan TN Tita, MD
      • Contact: Nancy Saxon, RN; Phone Number: 205-934-1616; Email: nbsaxon@uabmc.edu
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • Regents of the University of California San Francisco
      • Principal Investigator: Mary Norton, MD
      • Contact: Natalie Oman, MPH; Phone Number: 206-718-4703; Email: natalie.oman@ucsf.edu
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Principal Investigator: Lynn Yee, MD
      • Contact: Elizabeth Rangel, RN; Email: elizabeth.rangel@northwestern.edu
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
      • Contact: Megan Loffredo, MD, CCRC; Phone Number: 203-722-1058; Email: ml4639@cumc.columbia.edu
      • Principal Investigator: Noelia Zork, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina - Chapel Hill
      • Contact: Kelly Clark, RN; Phone Number: 919-350-6117; Email: kelly_clark@med.unc.edu
      • Principal Investigator: John M Thorp, MD
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University
      • Contact: Jennifer Ferrara, RNC MSN; Phone Number: 919-681-6176; Email: jennifer.ferrara@duke.edu
      • Principal Investigator: Brenna L Hughes, MD MS
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • Recruiting
      • Case Western Reserve University
      • Principal Investigator: Kelly Gibson, MD
      • Contact: Abigail Pierse, BS; Phone Number: 216-778-8443; Email: apierse@metrohealth.org
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University
      • Principal Investigator: Maged Costantine, MD
      • Contact: Anna Bartholomew, RN, BSN; Phone Number: 614-685-3229; Email: anna.bartholomew@osumc.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Hospital of the University of Pennsylvania
      • Principal Investigator: Lorraine Dugoff, MD
      • Contact: Amee Feager, RN, BSN; Phone Number: 636-699-3433; Email: amee.feager@pennmedicine.upenn.edu
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • Magee Women's Hospital
      • Contact: Jeanette Boyce, RN; Phone Number: 412-527-8118; Email: tessje@upmc.edu
      • Principal Investigator: Hyagriv Simhan, MD, MS
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Recruiting
      • Brown Univeristy
      • Contact: Angelica DeMartino, RN, BSN; Phone Number: 48521 401-274-1122; Email: amdemartino@wihri.org
      • Principal Investigator: Dwight J Rouse, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
      • Principal Investigator: Catherine Eppes, MD, MPH
      • Contact: Christina Reed, RN, NP; Phone Number: 832-826-7377; Email: christina.reed@bcm.edu
      • Contact: Jia Chen, RN, CCRP; Phone Number: 713-798-3798; Email: jia.chen@bcm.edu
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas - Houston
      • Principal Investigator: Hector Mendez-Figueroa, MD
      • Contact: Felecia Ortiz, RN; Phone Number: 713-500-6467; Email: felecia.ortiz@uth.tmc.edu
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah
      • Principal Investigator: Torri Metz, MD
      • Contact: Amber Sowles, RN; Phone Number: 801-585-5499; Email: amber.sowles@hsc.utah.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azithromycin prophylaxis and 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.	Drug: Azithromycin Injection; 500mg azithromycin in 250 mL of normal saline; Drug: Standard of Care Preoperative antibiotics; standard of care preoperative antibiotics (excluding azithromycin) prior to incision
Placebo Comparator: Placebo and 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.	Drug: Standard of Care Preoperative antibiotics; standard of care preoperative antibiotics (excluding azithromycin) prior to incision; Drug: Placebo; 250 mL of normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal infection composite	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	Delivery up to 6 weeks postpartum (a period of up to 6 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-infections wound complications	any of the following wound complications without diagnosis of a wound infection: seroma, wound breakdown, erythema and/or hematoma	Delivery up to 6 weeks postpartum (a period of up to 6 weeks)
Perinatal composite outcome	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.	hospital discharge, 6 weeks of birth, or death (whichever occurs first)
Number of neonates with Allergic Reaction	Neonatal allergic reaction (e.g., skin rash) through discharge or 7 days from birth, whichever is earliest, suspected to be due to study medication.	birth through hospital discharge, or 7 days from birth, whichever is earliest
Number of Neonates with Gastrointestinal Symptoms	vomiting, diarrhea, feeding difficulty through discharge or 7 days from birth, whichever is earliest	birth through hospital discharge, or 7 days from birth, whichever is earliest
Number of Maternal Deaths	Death	From randomization through 6 weeks postpartum (a period of up to 6 weeks)
Maternal Resource Composite	Hospital readmission; Emergency room (ER) visit; Unscheduled clinic visits	From hospital discharge following delivery through 6 weeks postpartum (a period of up to 6 weeks)
Neonatal Resource Composite	Hospital readmission; Emergency Room (ER) visit	From hospital discharge following delivery through 6 weeks postpartum (a period of up to 6 weeks)
Maternal Hospital Length of Stay	Length of hospital stay in days	Hospital admission to hospital discharge (up to 42 days)
Rate of Neonatal ICU Admission	Number of neonates admitted to NICU	Delivery to hospital discharge (up to 120 days)
Number of Participants with Maternal Resistant Infection	bacteria and resistance patterns from clinical cultures	Randomization through 6 weeks postpartum (a period of up to 6 weeks)
Number of Neonates with Neonatal Resistant Infection	bacteria and resistance patterns from clinical cultures	From birth up to 6 weeks of age

Collaborators and Investigators

• Sponsor: The George Washington University Biostatistics Center
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of Alabama at Birmingham
• Investigators: Study Chair: Alan T.N. Tita, MD PhD, University of Alabama at Birmingham; Study Chair: Kim Boggess, MD, University of North Carolina, Chapel Hill; Study Director: Monica Longo, MD PhD, Eunice Kennedy Shriver NICHD; Principal Investigator: Rebecca G Clifton, PhD, The George Washington University Biostatistics Center

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2024
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: September 13, 2024
• First Submitted That Met QC Criteria: September 17, 2024
• First Posted (Actual): September 20, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: prevention; infection; antibiotics; cesarean delivery; maternal morbidity
• Additional Relevant MeSH Terms: Infections; Organic Chemicals; Macrolides; Lactones; Erythromycin; Polyketides; Azithromycin
• Other Study ID Numbers: HD036801-PRECEDE; U24HD036801 (U.S. NIH Grant/Contract); U01HD114634 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared via NICHD DASH in accordance with NIH policy.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No