Two-drug Antibiotic Prophylaxis in Scheduled Cesarean Deliveries

Wound Infection Clinical Trial

Official title:

Azithromycin-based Extended-spectrum Prophylaxis in Scheduled Cesarean Deliveries

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03960970
• Other study ID #: Prophylaxis Trial
• Status: Recruiting
• Phase: Phase 2
• Start date: September 15, 2019
• Est. completion date: November 30, 2020

Study information

• Verified date: September 2019
• Source: RWJ Barnabas Health at Jersey City Medical Center
• Contact: Tali Wajsfeld, MD
• Phone: 2019152000
• Email: tali.wajsfeld[@]rwjbh.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Cesarean deliveries are the most common surgical procedure performed in the United States, and scheduled cesarean deliveries account for at least 40% of all cesarean deliveries every year. A significant decrease in cesarean delivery associated maternal morbidity has been achieved with preoperative prophylactic single-dose cephalosporin given within 60 minutes of skin incision. Also, on laboring patients and/or with rupture of membranes, several studies suggest that adding azithromycin to standard cephalosporin prophylaxis is not only cost-effective but reduces overall rates of endometritis and wound infection. Azithromycin provides effective coverage against Ureaplasma, commonly 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. No increase in neonatal morbidity was noted with adjunctive azithromycin prophylaxis, including adverse events.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: November 30, 2020
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Cesarean Section; Infection
• Communicable Diseases
• Endometritis
• Infection
• Wound Infection

Intervention

Drug:
• Azithromycin 500 mg
Additional IV Azithromycin 500 mg to Standard Prophylaxis
• Mefoxin 2g
Standard Prophylaxis

Locations

Country	Name	City	State
United States	Jersey City Medical Center	Jersey City	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
RWJ Barnabas Health at Jersey City Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (12)

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 120: Use of prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2011 Jun;117(6):1472-83. doi: 10.1097/AOG.0b013e3182238c31. — View 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. — View Citation

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. — View Citation

Boggess KA, Tita A, Jauk V, Saade G, Longo S, Clark EA, 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. — View Citation

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. — View Citation

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. — View Citation

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

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. Review. — View Citation

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. — 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

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rates of Neonatal Intensive Care Unit (NICU) Admission	Neonatal Intensive Care Unit (NICU) Admission rather than prematurity	Up to 6 weeks after delivery
Other	Rates of Neonatal Readmission	Hospital readmission within 6 weeks of birth	Up to 6 weeks after delivery
Primary	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
Primary	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	Rates of Maternal Fever	Temperature equal or greater than 100.4F	Up to 6 weeks after delivery
Secondary	Rates of Maternal Postpartum Readmission or Unscheduled Visit	Admission to hospital or unscheduled appointment in additional to regular 1-week and 6-week postpartum visit	Up to 6 weeks after delivery
Secondary	Rates of Postpartum Antibiotic Use	Antibiotic use for any reason including other infections such as UTI and sepsis.	Up to 6 weeks after delivery
Secondary	Rates of Serious Adverse Events	MICU admission, thromboembolic events, sepsis, maternal death	Up to 6 weeks after delivery