Peri-operative Cefazolin Prophylaxis at Time of Cesarean Delivery in the Obese Gravida

Tracking Information
First Submitted Date ICMJE	July 10, 2013
First Posted Date ICMJE	July 22, 2013
Last Update Posted Date	August 18, 2014
Study Start Date ICMJE	August 2013
Actual Primary Completion Date	April 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 17, 2013)	Plasma area under the curve (AUC) of cefazolin [ Time Frame: Within the first 8 hours after skin incision ]; The primary aim of this study will be to evaluate the plasma area under the curve (AUC) of cefazolin in both the 2 grams and 3 grams groups. Blood samples will be obtained prior to administration of cefazolin and then 15 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 4 hours, 6 hours and 8 hours from administration of cefazolin
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01904500 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 14, 2013)	Adipose tissue concentrations of cefazolin [ Time Frame: Adipose tissue samples will be assessed at time of skin incision, hysterotomy closure and then fascial closure. ]; Cmax [ Time Frame: Within the first 8 hours after skin incision ]; Drug Clearance (Cl) [ Time Frame: Within the first 8 hours after skin incision ]; Volume of distribution (Vd) [ Time Frame: Within the first 8 hours after skin incision ]; Absolute drug concentrations in plasma and tissue [ Time Frame: Within the first 8 hours after skin incision ]; Tissue to Plasma (T/P) Drug Concentration Ratios [ Time Frame: Within the first 8 hours after skin incision ]; Surgical site infection fo any type [ Time Frame: Participants will be followed for the duration of their hospital stay and will be called at 6 weeks from surgery ]; Cord blood concentration [ Time Frame: At time of delivery ]; Urine drug concentration [ Time Frame: 8 hours ]Samples to be obtained up to 8 hours post cesarean delivery
Original Secondary Outcome Measures ICMJE; (submitted: July 17, 2013)	Adipose tissue concentrations of cefazolin [ Time Frame: Adipose tissue samples will be assessed at time of skin incision, hysterotomy closure and then fascial closure. ]; Cmax [ Time Frame: Within the first 8 hours after skin incision ]; Drug Clearance (Cl) [ Time Frame: Within the first 8 hours after skin incision ]; Volume of distribution (Vd) [ Time Frame: Within the first 8 hours after skin incision ]; Absolute drug concentrations in plasma and tissue [ Time Frame: Within the first 8 hours after skin incision ]; Tissue to Plasma (T/P) Drug Concentration Ratios [ Time Frame: Within the first 8 hours after skin incision ]; Surgical site infection fo any type [ Time Frame: Participants will be followed for the duration of their hospital stay and will be called at 6 weeks from surgery ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Peri-operative Cefazolin Prophylaxis at Time of Cesarean Delivery in the Obese Gravida
Official Title ICMJE	Peri-operative Cefazolin Prophylaxis at Time of Cesarean Delivery in the Obese Gravida
Brief Summary	Obesity has become an increasingly prevalent public health problem in the United States, reaching epidemic proportions. According to 2009 CDC epidemiologic data on obesity in the United States, 35.7% of the United States population is considered overweight or obese. Currently, on the review of the literature, over 20% of pregnancies in this country are complicated by maternal obesity. Obesity has been well demonstrated to be correlated with numerous adverse pregnancy outcomes such hypertensive disorders of pregnancy, gestational diabetes, and increased rates of operative delivery. Moreover, obesity, irrespective of pregnancy, has been demonstrated to be an independent risk factor for the development of postoperative surgical site infections. Development of such infections can have both consequential long-term medical sequelae for patients and economic impacts on the health care system at large. Cefazolin, a first generation hydrophilic cephalosporin whose clearance is exclusively mediated via the kidneys unchanged, is used as pre-operative antibiotic prophylaxis for cesarean deliveries. The current accepted standard of care is to administer 2 grams of cefazolin within 60 minutes of skin incision. Studies of drug concentrations of cephalosporins for pre-operative antibiotic prophylaxis in obese bariatric patients have shown that therapeutic concentrations may not be achieved in both tissue and plasma. Limited data exist in pregnancy. Therefore, it is the goal of this study to investigate whether obese patients presenting for cesarean delivery require an increased dosing amount of pre-operative antibiotic prophylaxis. This study will randomized women with a pre-pregnancy body mass index of 30 kg/m2 or more who are presenting for their scheduled cesarean delivery to receive either 2 grams or 3 grams of cefazolin for pre-operative antibiotic prophylaxis. By drawing blood at specific time points in the peri-operative period and extracting adipose tissue samples during cesarean delivery, this study will investigate the pharmacokinetics of cefazolin in both the plasma and tissues of the obese gravida.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition ICMJE	Obesity; Pregnancy
Intervention ICMJE	Drug: Pre-operative cefazolin
Study Arms	Cefazolin 2 grams Intervention: Drug: Pre-operative cefazolin; Active Comparator: Cefazolin 3 grams Intervention: Drug: Pre-operative cefazolin
Publications *	Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity in the United States, 2009-2010. NCHS Data Brief. 2012 Jan;(82):1-8.; 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.; Dinsmoor MJ, Gilbert S, Landon MB, Rouse DJ, Spong CY, Varner MW, Caritis SN, Wapner RJ, Sorokin Y, Miodovnik M, O'Sullivan MJ, Sibai BM, Langer O; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Perioperative antibiotic prophylaxis for nonlaboring cesarean delivery. Obstet Gynecol. 2009 Oct;114(4):752-6. doi: 10.1097/AOG.0b013e3181b8f28f.; Pai MP, Bearden DT. Antimicrobial dosing considerations in obese adult patients. Pharmacotherapy. 2007 Aug;27(8):1081-91. Review.; Pevzner L, Swank M, Krepel C, Wing DA, Chan K, Edmiston CE Jr. Effects of maternal obesity on tissue concentrations of prophylactic cefazolin during cesarean delivery. Obstet Gynecol. 2011 Apr;117(4):877-82. doi: 10.1097/AOG.0b013e31820b95e4.; Craig WA. Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins. Diagn Microbiol Infect Dis. 1995 May-Jun;22(1-2):89-96. Review.; 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.; Ho VP, Nicolau DP, Dakin GF, Pomp A, Rich BS, Towe CW, Barie PS. Cefazolin dosing for surgical prophylaxis in morbidly obese patients. Surg Infect (Larchmt). 2012 Feb;13(1):33-7. doi: 10.1089/sur.2010.097. Epub 2012 Feb 8.; van Kralingen S, Taks M, Diepstraten J, van de Garde EM, van Dongen EP, Wiezer MJ, van Ramshorst B, Vlaminckx B, Deneer VH, Knibbe CA. Pharmacokinetics and protein binding of cefazolin in morbidly obese patients. Eur J Clin Pharmacol. 2011 Oct;67(10):985-92. doi: 10.1007/s00228-011-1048-x. Epub 2011 Apr 16.; Toma O, Suntrup P, Stefanescu A, London A, Mutch M, Kharasch E. Pharmacokinetics and tissue penetration of cefoxitin in obesity: implications for risk of surgical site infection. Anesth Analg. 2011 Oct;113(4):730-7. doi: 10.1213/ANE.0b013e31821fff74. Epub 2011 Jun 3.; Liu P, Derendorf H. Antimicrobial tissue concentrations. Infect Dis Clin North Am. 2003 Sep;17(3):599-613. Review.; Forse RA, Karam B, MacLean LD, Christou NV. Antibiotic prophylaxis for surgery in morbidly obese patients. Surgery. 1989 Oct;106(4):750-6; discussion 756-7.; Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control. 1999 Apr;27(2):97-132; quiz 133-4; discussion 96.; Allegaert K, van Mieghem T, Verbesselt R, de Hoon J, Rayyan M, Devlieger R, Deprest J, Anderson BJ. Cefazolin pharmacokinetics in maternal plasma and amniotic fluid during pregnancy. Am J Obstet Gynecol. 2009 Feb;200(2):170.e1-7. doi: 10.1016/j.ajog.2008.08.067. Epub 2008 Nov 11.; Philipson A, Stiernstedt G, Ehrnebo M. Comparison of the pharmacokinetics of cephradine and cefazolin in pregnant and non-pregnant women. Clin Pharmacokinet. 1987 Feb;12(2):136-44.; Kato Y, Takahara S, Kato S, Kubo Y, Sai Y, Tamai I, Yabuuchi H, Tsuji A. Involvement of multidrug resistance-associated protein 2 (Abcc2) in molecular weight-dependent biliary excretion of beta-lactam antibiotics. Drug Metab Dispos. 2008 Jun;36(6):1088-96. doi: 10.1124/dmd.107.019125. Epub 2008 Mar 13.; Sakurai Y, Motohashi H, Ogasawara K, Terada T, Masuda S, Katsura T, Mori N, Matsuura M, Doi T, Fukatsu A, Inui K. Pharmacokinetic significance of renal OAT3 (SLC22A8) for anionic drug elimination in patients with mesangial proliferative glomerulonephritis. Pharm Res. 2005 Dec;22(12):2016-22. Epub 2005 Nov 1.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Estimated Enrollment ICMJE; (submitted: July 17, 2013)	26
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	April 2014
Actual Primary Completion Date	April 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Body mass index (BMI) greater than 30kg/m2; Those women having scheduled primary or repeat cesarean delivery Exclusion Criteria: Type 1 and Type 2 Insulin Dependent Diabetes Mellitus; Autoimmune disease, including systemic lupus erythematosus; History of chronic renal disease; Those using chronic corticosteroids; Those with a history of a previous wound breakdown; Those who have an allergy to cephalosporins whose reaction includes anaphylaxis, urticaria or other systemic consequences; Those who are unable to receive their antibiotics in a timely fashion
Sex/Gender	Sexes Eligible for Study: Female
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01904500
Other Study ID Numbers ICMJE	PRO13040497
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Omar M Young, MD, University of Pittsburgh
Study Sponsor ICMJE	University of Pittsburgh
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Omar Young, MD Clinical Fellow, Division of Maternal-Fetal Medicine
PRS Account	University of Pittsburgh
Verification Date	August 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP