Azithromycin Prophylaxis for PRElabor CEsarean DElivery Trial

NCT06605118 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: HD036801-PRECEDEU01HD114634U24HD036801
• Study Type: interventional
• Target: 8,000
• Locations: 1 country
• Sites: 14

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.

Conditions

Obstetrical Complications; Labor and Delivery Complication; Cesarean Delivery

Keywords

cesarean delivery; infection; maternal morbidity; antibiotics; prevention

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Non-infections wound complications

  Delivery up to 6 weeks postpartum (a period of up to 6 weeks)

• Perinatal composite outcome

  hospital discharge, 6 weeks of birth, or death (whichever occurs first)

• Number of neonates with Allergic Reaction

  birth through hospital discharge, or 7 days from birth, whichever is earliest

• Number of Neonates with Gastrointestinal Symptoms

  birth through hospital 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)

Study Arms (2)

Azithromycin prophylaxis and standard of care preoperative antibiotics

EXPERIMENTAL

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; Drug: Standard of Care Preoperative antibiotics

Placebo and standard of care preoperative antibiotics

PLACEBO COMPARATOR

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: Placebo; Drug: Standard of Care Preoperative antibiotics

Interventions

Azithromycin Injection DRUG

500mg azithromycin in 250 mL of normal saline

Azithromycin prophylaxis and standard of care preoperative antibiotics

Placebo DRUG

250 mL of normal saline

Placebo and standard of care preoperative antibiotics

Standard of Care Preoperative antibiotics DRUG

standard of care preoperative antibiotics (excluding azithromycin) prior to incision

Azithromycin prophylaxis and standard of care preoperative antibiotics; Placebo and standard of care preoperative antibiotics

Eligibility Criteria

• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: collaborator
• The George Washington University Biostatistics Center: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (14)

University of Alabama - Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

Regents of the University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Duke University

Durham, North Carolina, 27710, United States

RECRUITING

Case Western Reserve University

Cleveland, Ohio, 44109, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Magee Women's Hospital

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Brown Univeristy

Providence, Rhode Island, 02905, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

University of Texas - Houston

Houston, Texas, 77030, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84132, United States

RECRUITING

MeSH Terms

Conditions

Infections

Interventions

Azithromycin

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Alan T.N. Tita, MD PhD

  University of Alabama at Birmingham

  STUDY CHAIR

• Kim Boggess, MD

  University of North Carolina, Chapel Hill

  STUDY CHAIR

• Monica Longo, MD PhD

  Eunice Kennedy Shriver NICHD

  STUDY DIRECTOR

• Rebecca G Clifton, PhD

  The George Washington University Biostatistics Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca G Clifton, PhD

CONTACT

301-881-9260; rclifton@bsc.gwu.edu

Steven Weiner, MS

CONTACT

weiner@bsc.gwu.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study medication will be prepared by the center research pharmacies from a list provided by the independent data coordinating center, with the active and placebo medication having identical appearance. No other individuals, including the participant or any other clinical or research staff will be informed of the study assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized shortly before delivery to receive either azithromycin administered intravenously or a placebo control of normal saline administered intravenously

Study Record Dates

• First Submitted: September 13, 2024
• First Posted: September 20, 2024
• Study Start: November 6, 2024
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF

Locations

US (14)