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

Study Overview
=================
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.

Official Title
-----------------
Cesarean Section Optimal Antibiotic Prophylaxis Trial

Conditions
-----------------
Endometritis, Wound Infection, Abscess, Surgical Site Infection

Intervention / Treatment
-----------------
* Drug: Azithromycin and standard of care
* Drug: Placebo and standard of care


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 14 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo and standard of care<br>250 cc normal saline | Drug: Placebo and standard of care<br>* 250 cc normal saline, plus standard of care (cephazolin or clindamycin)<br>* Other names: normal saline;|
| Experimental: Azithromycin and Standard of care<br>500 mg Azithromycin in 250 cc normal saline | Drug: Azithromycin and standard of care<br>* 500 mg in 250 cc normal saline 1 time dose plus standard of care (cephazolin or clindamycin)<br>* Other names: Zithromax;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Endometritis and/or Wound Infection and/or Other Post-cesarean Infections (Occurring Within 6 Weeks of 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. | Up to 6 weeks after delivery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pregnancy, Cesarean section, Antibiotic, Infections