Study of Effectiveness and Safety of Azithromycin-based Extended-spectrum Prophylaxis to Prevent Post Cesarean Infection

Not Applicable

Completed

Interventions: Drug: Placebo and standard of care
Drug: Azithromycin and standard of care

Brief Summary: The Cesarean Section Optimal Antibiotic Prophylaxis (C/SOAP) study is a large pragmatic multi-center randomized clinical trial designed to evaluate the comparative effectiveness and safety of azithromycin-based extended-spectrum antibiotic prophylaxis (azithromycin plus standard narrow-spectrum cephalosporin) relative to standard single-agent cephalosporin (preferably prior to surgical incision) to prevent post-cesarean infection.

Hypothesis: Compared to narrow-spectrum prophylaxis (i.e. cefazolin alone, or clindamycin if cephalosporin allergy) prior to surgical incision, the addition of extended-spectrum prophylaxis (azithromycin + cefazolin) reduces the incidence of post-cesarean infection.

Recruitment & Eligibility

Inclusion Criteria

Pregnant Women aged 14 years and over at ≥ 24 weeks' viable gestation who will undergo unscheduled/non-elective cesareans with either:

Labor (spontaneous or induced): active labor (ongoing contractions and at least 4cm dilated or contractions for at least 4 hours with documented cervical change of ≥1cm dilatation or ≥50% effacement), or
Membrane rupture (standardized to duration of at least 4 hours prior to randomization).

Exclusion Criteria

Patient unwilling or unable to provide consent
Multiple pregnancy
Known azithromycin (or other macrolide) allergy
Vaginal delivery
Elective or scheduled cesarean prior to labor or membrane rupture.
Azithromycin, erythromycin or other macrolide antibiotic use within 7 days of enrollment.
Clinical chorioamnionitis or any other active bacterial infection (e.g. pyelonephritis, pneumonia, abscess) at time of randomization.
Patient is unable or unlikely to follow-up after delivery (e.g. no prenatal care or a non-resident patient)
Fetal demise or major congenital anomaly
Significant liver disease defined as known cirrhosis or elevated transaminases of at least 3-fold upper limit of normal
Significant renal disease defined as serum creatinine known to be >2.0 mg/dl or on dialysis.
Active congestive heart failure (EF<45%) or pulmonary edema
Active diarrhea at time of delivery
Any patient with significant electrolyte abnormalities such as hypokalemia or hypocalcemia
Any patient with structural heart disease or arrhythmias, or taking any medications known to prolong the QT interval
Patient currently being treated with efavirenz, nelfinavir or fluconazole

Arm && Interventions

Group	Intervention	Description
Placebo and standard of care	Placebo and standard of care	250 cc normal saline
Azithromycin and Standard of care	Azithromycin and standard of care	500 mg Azithromycin in 250 cc normal saline

Primary Outcome Measures

Name	Time	Method
Participants With Endometritis and/or Wound Infection and/or Other Post-cesarean Infections (Occurring Within 6 Weeks of Delivery)	Up to 6 weeks after delivery	Endometritis was defined as the presence of at least two of the following signs with no other recognized cause: fever (temperature of at least 38°C \[100.4°F\]), abdominal pain, uterine tenderness, or purulent drainage from the uterus. Wound infection was defined as the presence of either superficial or deep incisional surgical-site infection characterized by cellulitis or erythema and induration around the incision or purulent discharge from the incision site with or without fever and included necrotizing fasciitis. Wound hematoma, seroma, or breakdown alone in the absence of the preceding signs did not constitute infection.

Secondary Outcome Measures

Name	Time	Method

Locations (9): Ochsner Clinic Foundation
🇺🇸
New Orleans, Louisiana, United States
Columbia University
🇺🇸
New York, New York, United States
University of Texas Medical Branch
🇺🇸
Galveston, Texas, United States
Mission Hospital
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Asheville, North Carolina, United States
University of Mississippi Medical Center
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Jackson, Mississippi, United States
University of Texas Health Science Center at Houston
🇺🇸
Houston, Texas, United States
University of Utah
🇺🇸
Salt Lake City, Utah, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
University of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States