Clinical trial NCT02049944: Increased Cefazolin During Cesarean Delivery in Obese Population
Official title: Increased Cefazolin (Ancef) Dosing for Prophylaxis During Cesarean Delivery in the Obese Population
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
Obesity, Morbid
Pregnancy
Infection; Cesarean Section
Keywords: Antibiotic Prophylaxis
Obesity
Obesity, Morbid
Pregnancy
Infection; Cesarean Section
Lead sponsor: MemorialCare Health System
Sponsor class: OTHER
Collaborators: name: University of California, Irvine
First posted: 2014-01-30
Enrollment: 30
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether an increased prophylactic dose (3 grams) of cefazolin at the time of cesarean delivery has superior coverage in adipose tissue than the current established dosing of 2 grams. The tissue and serum concentration values, when using an increased prophylactic dose, can then be compared to our pilot study assays in hopes of determining an optimal dosing for the obese and morbidly obese populations undergoing cesarean delivery.

A previous study performed at University of California, Irvine (UCI) and Long Beach Memorial Medical Center/Miller Children's Hospital (LBMMC) showed that the standard dose of antibiotics (2 grams of cefazolin) did not provide adequate coverage for all organisms in the obese and extremely obese populations. The purpose of this research study is to evaluate whether in increased dose of antibiotics given before cesarean delivery (3 grams of cefazolin) will reach adequate levels in adipose (fat cells underneath the skin) and serum (blood) samples. In addition, researchers hope to evaluate if/how the mother's weight has an effect on the levels of antibiotics in the tissues (a group of similar cells).

This follow up study (prior study HS# 2009-7015 at UCI) will enroll obese (Body Mass Index (BMI) of 30-40) and morbidly obese (BMI \>40) women to receive an increased dose of prophylactic cefazolin at time of scheduled cesarean delivery at both UCI and LBMMC. Researchers hope to enroll a total of 35 women overall.

Detailed description: Study Design:

This is a follow-up to the original pilot study (HS# 2009-7015 at UCI/587-08 at LBMMC). This study is also designed to be a prospective, non-randomized, non-blinded trial of the effects of obesity on adequacy of antimicrobial (cefazolin) concentrations with increased doses (from 2 grams to 3 grams) of preoperative prophylactic antibiotics within adipose tissues at the time of cesarean delivery.

Inclusion Criteria:

• Patients at term (\>37 weeks) undergoing a cesarean delivery at LBMMC and UCI.

Exclusion criteria:

* pre-gestational diabetes
* chronic hypertension
* collagen vascular disease
* renal impairment
* multiple gestation
* contraindications to cefazolin administration (known anaphylactic reaction to penicillin's or known cephalosporin allergy)
* any exposure to cephalosporins in one week prior to cesarean section
* need for emergent cesarean delivery or diagnosis of chorioamnionitis

Study Procedure:

All patients requiring cesarean delivery under non-emergent circumstances, as determined by their physician, will be approached for participation in study by co-investigators. They will be approached on Labor and Delivery during their intake evaluation on the day of their scheduled procedure. Based on published literature and preliminary power analysis we expect that each of the 2 study groups will need 1414 subjects to demonstrate statistically significant difference in antibiotic concentrations within adipose tissue. The two groups will consist of:

1. OBESE GROUP (BMI 30-40)
2. MORBIDLY OBESE GROUP (BMI \>40)

   1. All subjects will receive cefazolin at least 30, but no more than 60 minutes prior to skin incision.
   2. At the time of cesarean delivery, the following tissue samples will be collected:

      * adipose tissue immediately following skin incision (prior to incision of the fascia) and
      * adipose tissue prior to skin closure
      * serum sample after skin incision but prior to completion of the operative procedure

Approximately 2 grams of tissue sampled from each site and 5 cc of blood will be required for analysis.

All samples will be collected by Dr. Swank, Dr. Wing or a physician who had previously been proctored in the proper tissue collecting techniques by either of the above mentioned investigators. Upon collection, tissue specimens will be blotted to remove residual blood and debris, weighed, and placed in a freezer (-80'C) until analysis. Serum samples will be drawn into red top tubes and immediately placed on wet ice. Immediately following completion of the surgery, they will then be centrifuged for 10 minutes at 3G (3200 rpm) and placed in a locked -80'C freezer until analysis.

Tissue and serum samples will then be sent to David P. Nicolau, PhD, FCCP, FIDSA, at the Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut. Samples will be batched and sent all together at the completion of study enrollment. Dr. Swank and the study nurse will be responsible for securely packing samples on dry ice and overnight shipping them to Dr. Nicolau. Once with Dr. Nicolau, the tissue samples will be homogenized and analyzed to determine zones of inhibition. The Cefazolin concentrations will be determined in the serum samples using a previously validated high-performance liquid chromatography method. 16 Tissues and serum will be sent without direct identifiers. Dr. Nicolau will not have access to the identity of the research subjects providing the samples.

Eligibility criteria: Inclusion Criteria:

* Patients at term (\>37 weeks) undergoing a cesarean delivery at Women's Pavilion at Miller Children's Hospital and University of California, Irvine.

Exclusion Criteria:

* pre-gestational diabetes
* chronic hypertension
* collagen vascular disease
* renal impairment
* multiple gestation
* contraindications to Cefazolin administration (known anaphylactic reaction to penicillin's or known cephalosporin allergy)
* any exposure to cephalosporins in one week prior to cesarean section
* need for emergent cesarean delivery or diagnosis of chorioamnionitis

Primary outcomes:
measure: Achievement of Minimal Inhibitory Concentrations Within Adipose and Serum Sampled at Time of Cesarean Delivery
timeFrame: Each participant is to be observed per routine operative and post-operative guidelines, inpatient for 3-4 days.
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: MemorialCare Center for Women at Miller Children's Hospital Long Beach and Long Beach Memorial Medical Center
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
Study officials:
affiliation: MemorialCare Center for Women at Miller Children's Hospital Long Beach and Long Beach Memorial Medical Center
name: Jennifer McNulty, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Irvine
name: Deborah A Wing, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Irvine
name: Morgan Swank, MD
role: PRINCIPAL_INVESTIGATOR
References: