Study of Effectiveness and Safety of Azithromycin-based Extended-spectrum Prophylaxis to Prevent Post Cesarean Infection (C/SOAP)

Alan Tita

Status: Completed

Conditions: Surgical Site Infection; Endometritis; Wound Infection; Abscess

Treatments: Drug: Placebo and standard of care; Drug: Azithromycin and standard of care

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01235546

F090323006

NIH 1R01HD064729-01A1 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment: 2,013 patients

Sex: Female

Ages: 14+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

1. 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
2. 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,013 participants in 2 patient groups, including a placebo group

Placebo and standard of care

Placebo Comparator group

Description:

250 cc normal saline

Treatment:

Drug: Placebo and standard of care

Azithromycin and Standard of care

Experimental group

Description:

500 mg Azithromycin in 250 cc normal saline

Treatment:

Drug: Azithromycin and standard of care