Study of Effectiveness and Safety of Azithromycin-based Extended-spectrum Prophylaxis to Prevent Post Cesarean Infection (C/SOAP)
Primary Purpose
Endometritis, Wound Infection, Abscess
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Azithromycin and standard of care
Placebo and standard of care
Sponsored by
About this trial
This is an interventional prevention trial for Endometritis focused on measuring Pregnancy, Cesarean section, Antibiotic, Infections
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
Sites / Locations
- University of Alabama at Birmingham
- Ochsner Clinic Foundation
- University of Mississippi Medical Center
- Columbia University
- Mission Hospital
- University of North Carolina
- University of Texas Medical Branch
- University of Texas Health Science Center at Houston
- University of Utah
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo and standard of care
Azithromycin and Standard of care
Arm Description
250 cc normal saline
500 mg Azithromycin in 250 cc normal saline
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01235546
First Posted
November 4, 2010
Last Updated
June 29, 2017
Sponsor
Alan Tita
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), University of Texas, University of North Carolina, Mission Hospital, Ochsner Health System, The University of Texas Health Science Center, Houston, Columbia University, University of Utah, University of Mississippi Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT01235546
Brief Title
Study of Effectiveness and Safety of Azithromycin-based Extended-spectrum Prophylaxis to Prevent Post Cesarean Infection
Acronym
C/SOAP
Official Title
Cesarean Section Optimal Antibiotic Prophylaxis Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
May 2011 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Alan Tita
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), University of Texas, University of North Carolina, Mission Hospital, Ochsner Health System, The University of Texas Health Science Center, Houston, Columbia University, University of Utah, University of Mississippi Medical Center
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometritis, Wound Infection, Abscess, Surgical Site Infection
Keywords
Pregnancy, Cesarean section, Antibiotic, Infections
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2013 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo and standard of care
Arm Type
Placebo Comparator
Arm Description
250 cc normal saline
Arm Title
Azithromycin and Standard of care
Arm Type
Experimental
Arm Description
500 mg Azithromycin in 250 cc normal saline
Intervention Type
Drug
Intervention Name(s)
Azithromycin and standard of care
Other Intervention Name(s)
Zithromax
Intervention Description
500 mg in 250 cc normal saline 1 time dose plus standard of care (cephazolin or clindamycin)
Intervention Type
Drug
Intervention Name(s)
Placebo and standard of care
Other Intervention Name(s)
normal saline
Intervention Description
250 cc normal saline, plus standard of care (cephazolin or clindamycin)
Primary Outcome Measure Information:
Title
Participants With Endometritis and/or Wound Infection and/or Other Post-cesarean Infections (Occurring Within 6 Weeks of Delivery)
Description
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.
Time Frame
Up to 6 weeks after delivery
Other Pre-specified Outcome Measures:
Title
Neonatal Morbidities (Listed Below)
Description
morbidities include: death, Respiratory Distress Syndrome (RDS), Bronchopulmonary Dysplasia (BPD), Periventricular Leukomalacia (PVL) suspected or proven sepsis, Necrotizing Enterocolitis (NEC) Intraventricular Hemorrhage (IVH) and systemic inflammatory response syndrome
Time Frame
Up to 3 months after birth
Title
Neonatal Intensive Care Unit (NICU) Admission
Description
Neonates who are admitted to the NICU due to morbidities diagnosed from birth and up to three months of life. Morbidities as defined in the Neonatal morbidities outcome measure.
Time Frame
Up to 3 months after birth
Title
Neonatal Readmission
Time Frame
Up to 3 months after birth
Title
Maternal Fever
Time Frame
Up to 6 weeks after delivery
Title
Maternal Postpartum Readmission or Unscheduled Visit
Description
Maternal postpartum unscheduled visit or readmission to the hospital
Time Frame
Up to 6 weeks after delivery
Title
Maternal Postpartum Antibiotic Use
Description
Maternal postpartum use of antibiotics
Time Frame
Up to 6 weeks after delivery
Title
Maternal Serious Adverse Events
Description
All maternal serious adverse events
Time Frame
Up to 6 weeks after delivery
Title
Neonatal Serious Adverse Events
Description
Composite for all neonatal serious adverse events
Time Frame
Up to 3 months after birth
Title
Infant Pyloric Stenosis
Description
Any diagnosis of pyloric stenosis based on clinical presentation and radiological and/or surgical confirmation
Time Frame
up to 3 months after birth
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan TN Tita, MD, PhD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Mission Hospital
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7516
Country
United States
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555-0587
Country
United States
Facility Name
University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77225
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
19300334
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.
Results Reference
background
PubMed Identifier
12798523
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.
Results Reference
background
PubMed Identifier
18165392
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.
Results Reference
background
PubMed Identifier
35675601
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.
Results Reference
derived
PubMed Identifier
28178058
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.
Results Reference
derived
PubMed Identifier
27682034
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.
Results Reference
derived
Learn more about this trial
Study of Effectiveness and Safety of Azithromycin-based Extended-spectrum Prophylaxis to Prevent Post Cesarean Infection
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