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

Study Overview
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Brief Summary
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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.

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

Conditions
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Obesity, Pregnancy

Intervention / Treatment
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* Drug: Pre-operative cefazolin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cefazolin 2 grams<br> | Drug: Pre-operative cefazolin<br> <br> |
| Active Comparator: Cefazolin 3 grams<br> | Drug: Pre-operative cefazolin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma area under the curve (AUC) of cefazolin | 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 | Within the first 8 hours after skin incision | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adipose tissue concentrations of cefazolin |  | Adipose tissue samples will be assessed at time of skin incision, hysterotomy closure and then fascial closure. | 
| Cmax |  | Within the first 8 hours after skin incision | 
| Drug Clearance (Cl) |  | Within the first 8 hours after skin incision | 
| Volume of distribution (Vd) |  | Within the first 8 hours after skin incision | 
| Absolute drug concentrations in plasma and tissue |  | Within the first 8 hours after skin incision | 
| Tissue to Plasma (T/P) Drug Concentration Ratios |  | Within the first 8 hours after skin incision | 
| Surgical site infection fo any type |  | Participants will be followed for the duration of their hospital stay and will be called at 6 weeks from surgery | 
| Cord blood concentration |  | At time of delivery | 
| Urine drug concentration | Samples to be obtained up to 8 hours post cesarean delivery | 8 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cesarean delivery