Clinical trial NCT01235546: Study of Effectiveness and Safety of Azithromycin-based Extended-spectrum Prophylaxis to Prevent Post Cesarean Infection
Official title: Cesarean Section Optimal Antibiotic Prophylaxis Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Endometritis
Wound Infection
Abscess
Surgical Site Infection
Keywords: Pregnancy
Cesarean section
Antibiotic
Infections
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: University of Texas
name: University of North Carolina
name: Mission Hospital
name: Ochsner Health System
name: The University of Texas Health Science Center, Houston
name: Columbia University
name: University of Utah
name: University of Mississippi Medical Center
First posted: 2010-11-05
Enrollment: 2013
Sex: FEMALE
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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:

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

Primary outcomes:
measure: Participants With Endometritis and/or Wound Infection and/or Other Post-cesarean Infections (Occurring Within 6 Weeks of Delivery)
timeFrame: Up to 6 weeks after delivery
Secondary outcomes:
Other outcomes:
measure: Neonatal Morbidities (Listed Below)
timeFrame: Up to 3 months after birth
measure: Neonatal Intensive Care Unit (NICU) Admission
timeFrame: Up to 3 months after birth
measure: Neonatal Readmission
timeFrame: Up to 3 months after birth
measure: Maternal Fever
timeFrame: Up to 6 weeks after delivery
measure: Maternal Postpartum Readmission or Unscheduled Visit
timeFrame: Up to 6 weeks after delivery
measure: Maternal Postpartum Antibiotic Use
timeFrame: Up to 6 weeks after delivery
measure: Maternal Serious Adverse Events
timeFrame: Up to 6 weeks after delivery
measure: Neonatal Serious Adverse Events
timeFrame: Up to 3 months after birth
measure: Infant Pyloric Stenosis
timeFrame: up to 3 months after birth
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: New York
country: United States
facility: Columbia University
state: New York
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Alabama at Birmingham
name: Alan TN Tita, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tita ATN, Rouse DJ, Blackwell S, Saade GR, Spong CY, Andrews WW. Emerging concepts in antibiotic prophylaxis for cesarean delivery: a systematic review. Obstet Gynecol. 2009 Mar;113(3):675-682. doi: 10.1097/AOG.0b013e318197c3b6.
citation: Andrews WW, Hauth JC, Cliver SP, Savage K, Goldenberg RL. Randomized clinical trial of extended spectrum antibiotic prophylaxis with coverage for Ureaplasma urealyticum to reduce post-cesarean delivery endometritis. Obstet Gynecol. 2003 Jun;101(6):1183-9. doi: 10.1016/s0029-7844(03)00016-4.
citation: Tita AT, Hauth JC, Grimes A, Owen J, Stamm AM, Andrews WW. Decreasing incidence of postcesarean endometritis with extended-spectrum antibiotic prophylaxis. Obstet Gynecol. 2008 Jan;111(1):51-6. doi: 10.1097/01.AOG.0000295868.43851.39.
citation: Sanusi A, Ye Y, Boggess K, Saade G, Longo S, Clark E, Esplin S, Cleary K, Wapner R, Owens M, Blackwell S, Szychowski JM, Tita ATN, Subramaniam A. Timing of Adjunctive Azithromycin for Unscheduled Cesarean Delivery and Postdelivery Infection. Obstet Gynecol. 2022 Jun 1;139(6):1043-1049. doi: 10.1097/AOG.0000000000004788. Epub 2022 May 2.
citation: Boggess KA, Tita A, Jauk V, Saade G, Longo S, Clark EAS, Esplin S, Cleary K, Wapner R, Letson K, Owens M, Blackwell S, Beamon C, Szychowski JM, Andrews W; Cesarean Section Optimal Antibiotic Prophylaxis Trial Consortium. Risk Factors for Postcesarean Maternal Infection in a Trial of Extended-Spectrum Antibiotic Prophylaxis. Obstet Gynecol. 2017 Mar;129(3):481-485. doi: 10.1097/AOG.0000000000001899.
citation: Tita AT, Szychowski JM, Boggess K, Saade G, Longo S, Clark E, Esplin S, Cleary K, Wapner R, Letson K, Owens M, Abramovici A, Ambalavanan N, Cutter G, Andrews W; C/SOAP Trial Consortium. Adjunctive Azithromycin Prophylaxis for Cesarean Delivery. N Engl J Med. 2016 Sep 29;375(13):1231-41. doi: 10.1056/NEJMoa1602044.