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

Surgical Site Infection Clinical Trial

— C/SOAP  

Official title:

Cesarean Section Optimal Antibiotic Prophylaxis Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01235546
• Other study ID #: F090323006
• Secondary ID: NIH 1R01HD064729
• Status: Completed
• Phase: N/A
• First received: November 4, 2010
• Last updated: June 14, 2016
• Start date: May 2011
• Est. completion date: December 2015

Study information

• Verified date: June 2016
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 2013
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 14 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Abscess
• Communicable Diseases
• Endometritis
• Infection
• Surgical Site Infection
• Surgical Wound Infection
• Wound Infection

Intervention

Drug:
• Azithromycin
500 mg in 250 cc normal saline 1 time dose
• Placebo
250 cc normal saline

Locations

Country	Name	City	State
United States	Mission Hospital	Ashville	North Carolina
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of North Carolina	Chapel Hill	North Carolina
United States	University of Texas Medical Branch	Galveston	Texas
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University	New York	New York
United States	University of Utah	Salt Lake City	Utah

Sponsors (10)

Lead Sponsor	Collaborator
Alan Tita	Columbia University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Mission Hospital, Ochsner Health System, The University of Texas Health Science Center, Houston, University of Mississippi Medical Center, University of North Carolina, University of Texas, University of Utah

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View Citation

Tita AT, 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):675-82. doi: 10.1097/AOG.0b013e318197c3b6. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Neonatal morbidities including death, RDS, BPD, PVL, suspected or proven sepsis, NEC, IVH and systemic inflammatory response syndrome		Up to 3 months after birth	Yes
Other	NICU admission		Up to 3 months after birth	Yes
Other	Neonatal readmission		Up to 3 months after birth	Yes
Other	Maternal fever		Up to 6 weeks after delivery	No
Other	Maternal postpartum readmission or unscheduled visit		Up to 6 weeks after delivery	No
Other	Maternal postpartum antibiotic use		Up to 6 weeks after delivery	No
Other	Composite Maternal serious adverse events		Up to 6 weeks after delivery	Yes
Other	Composite neonatal serious adverse events		Up to 3 months after birth	Yes
Other	Infant pyloric stenosis	Any diagnosis of pyloric stenosis based on clinical presentation and radiological and/or surgical confirmation	up to 3 months after birth	Yes
Other	Post-cesarean infection by chorioamnionic colonization with ureaplasmas	Does the impact of extended regimen vary by the presence or absence of ureaplasmas at randomization?	Up to 6 weeks after delivery	No
Other	Effect modifiers	Does the impact of extended prophylaxis vary by specific factors including obesity, wound size, duration from administration to incision	Up to 6 weeks after delivery	No
Primary	Composite of endometritis and/or wound infection and/or other post-cesarean infections (occurring within 6 weeks of delivery)		Up to 6 weeks after delivery	No
Secondary	Individual post-cesarean infections: Endometritis, wound infection (including necrotizing fascitis), other infections including abscess, septic thrombosis, pneumonia, pyelonephritis and breast infection		Up 6 weeks after delivery	No