Two-drug Antibiotic Prophylaxis in Scheduled Cesarean Deliveries

NCT03960970 | Unknown Phase 2 FDA Drug

• 1 other identifier: Prophylaxis Trial
• Study Type: interventional
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

Cesarean deliveries are the most common surgical procedure performed in the United States. A significant decrease in cesarean delivery associated maternal morbidity has been achieved with preoperative prophylactic single-dose cephalosporin, widely used before skin incision. Also, on laboring patients and/or with rupture of membranes, several studies suggest that adding azithromycin to standard cephalosporin prophylaxis is cost-effective and reduces overall rates of endometritis, wound infection, readmission, use of antibiotics and serious maternal events. Azithromycin has effective coverage against Ureaplasma, associated with increased rates of endometritis. Although two-drug regimen has been suggested for laboring and/or patients that undergo cesarean delivery, no studies have investigated the potential benefits of two-drug regimen in non-laboring patients.

Conditions

Endometritis; Cesarean Section; Infection; Wound Infection

Keywords

Cesarean Delivery; Endometritis; Wound Infection; Azithromycin; Antibiotic Prophylaxis

Outcome Measures

Primary Outcomes (2)

• Rates of Endometritis

  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.

  Up to 6 weeks after delivery

• Rates of Wound Infection

  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, abscess or breakdown alone in the absence of the preceding signs did not constitute infection.

  Up to 6 weeks after delivery

Secondary Outcomes (4)

• Rates of Maternal Fever

  Up to 6 weeks after delivery

• Rates of Maternal Postpartum Readmission or Unscheduled Visit

  Up to 6 weeks after delivery

• Rates of Postpartum Antibiotic Use

  Up to 6 weeks after delivery

• Rates of Serious Adverse Events

  Up to 6 weeks after delivery

Other Outcomes (2)

• Rates of Neonatal Intensive Care Unit (NICU) Admission

  Up to 6 weeks after delivery

• Rates of Neonatal Readmission

  Up to 6 weeks after delivery

Study Arms (2)

One-drug Prophylaxis

ACTIVE COMPARATOR

Mefoxin 2g IV, Piggyback, once

Drug: Mefoxin 2g

Two-drug Prophylaxis

EXPERIMENTAL

Mefoxin 2g IV, Piggyback, once and Azithromycin 500mg IV, Piggyback, once

Drug: Azithromycin 500 mg; Drug: Mefoxin 2g

Interventions

Azithromycin 500 mg DRUG

Additional IV Azithromycin 500 mg to Standard Prophylaxis

Two-drug Prophylaxis

Mefoxin 2g DRUG

Standard Prophylaxis

Also known as: Cefoxitin

One-drug Prophylaxis; Two-drug Prophylaxis

Eligibility Criteria

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

You may qualify if:

• Pregnant women 18 years or older
• Women undergoing primary or repeat cesarean delivery
• Singleton gestation
• Gestational age greater than 34 weeks
• Pregnant patients undergoing scheduled cesarean delivery
• Intact membranes
• Non-laboring
• Signed informed consent

You may not qualify if:

• Maternal age \< 18 years
• Multi-fetal gestation
• Known allergy to cephalosporin or azithromycin
• Patient unwilling or unable to provide consent
• Diagnosis of rupture of membranes
• Intraamniotic infection, or any other active bacterial infection (e.g. pyelonephritis, pneumonia, abscess) at time of randomization.
• Immunocompromising medical conditions: HIV positive with CD4 count below 200, chronic steroid use, current diagnosis of cancer and/or chemotherapy age use
• Emergent cesarean precluding consent or availability of study medication
• Need for hysterectomy at time of delivery
• Use of antibiotic in the 72 hours prior to admission, with exception to patient receiving antibiotics for GBS
• Inability to contact patient on postpartum period.

Sponsors & Collaborators

• RWJ Barnabas Health at Jersey City Medical Center: lead

Study Sites (1)

Jersey City Medical Center

Jersey City, New Jersey, 07302, United States

RECRUITING

Related Publications (12)

• 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

• 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 BACKGROUND

• 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 BACKGROUND

• Andrews WW, Shah SR, Goldenberg RL, Cliver SP, Hauth JC, Cassell GH. Association of post-cesarean delivery endometritis with colonization of the chorioamnion by Ureaplasma urealyticum. Obstet Gynecol. 1995 Apr;85(4):509-14. doi: 10.1016/0029-7844(94)00436-H.

  PMID: 7898825 BACKGROUND

• Harper LM, Kilgore M, Szychowski JM, Andrews WW, Tita ATN. Economic Evaluation of Adjunctive Azithromycin Prophylaxis for Cesarean Delivery. Obstet Gynecol. 2017 Aug;130(2):328-334. doi: 10.1097/AOG.0000000000002129.

  PMID: 28697108 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

• ACOG Practice Bulletin No. 120: Use of prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2011 Jun;117(6):1472-1483. doi: 10.1097/AOG.0b013e3182238c31. No abstract available.

  PMID: 21606770 BACKGROUND

• Skeith AE, Niu B, Valent AM, Tuuli MG, Caughey AB. Adding Azithromycin to Cephalosporin for Cesarean Delivery Infection Prophylaxis: A Cost-Effectiveness Analysis. Obstet Gynecol. 2017 Dec;130(6):1279-1284. doi: 10.1097/AOG.0000000000002333.

  PMID: 29112658 BACKGROUND

• Smith C, Egunsola O, Choonara I, Kotecha S, Jacqz-Aigrain E, Sammons H. Use and safety of azithromycin in neonates: a systematic review. BMJ Open. 2015 Dec 9;5(12):e008194. doi: 10.1136/bmjopen-2015-008194.

  PMID: 26656010 BACKGROUND

• Sutton AL, Acosta EP, Larson KB, Kerstner-Wood CD, Tita AT, Biggio JR. Perinatal pharmacokinetics of azithromycin for cesarean prophylaxis. Am J Obstet Gynecol. 2015 Jun;212(6):812.e1-6. doi: 10.1016/j.ajog.2015.01.015. Epub 2015 Jan 13.

  PMID: 25595580 BACKGROUND

• Smaill FM, Grivell RM. Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section. Cochrane Database Syst Rev. 2014 Oct 28;2014(10):CD007482. doi: 10.1002/14651858.CD007482.pub3.

  PMID: 25350672 BACKGROUND

MeSH Terms

Conditions

Endometritis; Infections; Wound Infection

Interventions

Azithromycin; Cefoxitin

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

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Cephamycins; Cephalosporins; beta-Lactams; Lactams; Amides; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Tali Wajsfeld, MD

  RWJ Barnabas Health at Jersey City Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tali Wajsfeld, MD

CONTACT

2019152000; tali.wajsfeld@rwjbh.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigador

Model Details: Pregnant patients admitted to Labor and Delivery unit between June 2019 and July 2020 will be randomized to received either standard prophylaxis or azithromycin and cephalosporin for preoperative prophylaxis after inclusion and exclusion criteria are met and informed consent for participation is signed.

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: May 23, 2019
• Study Start: September 15, 2019
• Primary Completion: September 30, 2019
• Study Completion: November 30, 2020
• Last Updated: September 17, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)