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

NCT01235546 | Completed Results DMC

• 2 other identifiers: F090323006NIH 1R01HD064729-01A1
• Study Type: interventional
• Target: 2,013
• Locations: 1 country
• Sites: 9

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.

Conditions

Endometritis; Wound Infection; Abscess; Surgical Site Infection

Keywords

Pregnancy; Cesarean section; Antibiotic; Infections

Outcome Measures

Primary Outcomes (1)

• 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

Other Outcomes (9)

• Neonatal Morbidities (Listed Below)

  Up to 3 months after birth

• Neonatal Intensive Care Unit (NICU) Admission

  Up to 3 months after birth

• Neonatal Readmission

  Up to 3 months after birth

Study Arms (2)

Placebo and standard of care

PLACEBO COMPARATOR

250 cc normal saline

Drug: Placebo and standard of care

Azithromycin and Standard of care

EXPERIMENTAL

500 mg Azithromycin in 250 cc normal saline

Drug: Azithromycin and standard of care

Interventions

Azithromycin and standard of care DRUG

500 mg in 250 cc normal saline 1 time dose plus standard of care (cephazolin or clindamycin)

Also known as: Zithromax

Azithromycin and Standard of care

Placebo and standard of care DRUG

250 cc normal saline, plus standard of care (cephazolin or clindamycin)

Also known as: normal saline

Placebo and standard of care

Eligibility Criteria

• Age: 14 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (9)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Mission Hospital

Asheville, North Carolina, 28801, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599-7516, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0587, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77225, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (7)

• 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.

  PMID: 19300334 BACKGROUND

• 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.

  PMID: 12798523 BACKGROUND

• 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.

  PMID: 18165392 BACKGROUND

• Martin JK, Longo SA, Jauk VR, Clark EAS, Saade GR, Boggess KA, Esplin S, Wapner RJ, Owens MY, Blackwell SC, Andrews WW, Szychowski JM, Tita AT. Neonatal outcomes in term and preterm infants following adjunctive azithromycin antibiotic prophylaxis for non-elective cesarean delivery. J Matern Fetal Neonatal Med. 2024 Dec;37(1):2367082. doi: 10.1080/14767058.2024.2367082. Epub 2024 Jun 14.

  PMID: 38873885 DERIVED

• 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.

  PMID: 35675601 DERIVED

• 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.

  PMID: 28178058 DERIVED

• 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.

  PMID: 27682034 DERIVED

MeSH Terms

Conditions

Endometritis; Wound Infection; Abscess; Surgical Wound Infection; Infections

Interventions

Azithromycin; Standard of Care; Saline Solution

Condition Hierarchy (Ancestors)

Pelvic Inflammatory Disease; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Uterine Diseases; Genital Diseases; Suppuration; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Postoperative Complications

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Alan Tita, MD
• Organization: University of Alabama at Birmingham, Maternal & Fetal Medicine

atita@uab.edu

205-934-9616

Study Officials

• Alan TN Tita, MD, PhD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 4, 2010
• First Posted: November 5, 2010
• Study Start: May 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: July 28, 2017
• Results First Posted: July 28, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)