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Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients

Primary Purpose

Congenital Heart Diseases, Aortic Valve Disorder

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Cefazolin 25 mg/kg body weight and Vancomycin hydrochloride
Cefazolin 30 mg/kg body weight
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Congenital Heart Diseases

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patient less than or equal to 1 year of age who is undergoing cardiovascular surgery requiring CPB or patient under 18 years of age undergoing procedures involving aortic valve or aorta
  2. Patients with a positive MRSA screen or a history of MRSA infections who are undergoing any cardiac surgery

Exclusion Criteria:

  1. Patients who have known hypersensitivity to vancomycin or cephalosporins
  2. Patients with renal insufficiency
  3. Patients who have received vancomycin or cephalosporins 48 hours prior to the day of surgery
  4. Patients whose surgery is due to an infection-related diagnosis such as endocarditis
  5. Patients whose parents do not wish to have them receive vancomycin prophylaxis
  6. Neonates born at less than 38 weeks gestational age

Sites / Locations

  • Lucile Packard Children's Hospital at Stanford

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Other

Arm Label

Cefazolin 25 mg/kg body weight and vancomycin

Cefazolin only 30mg/kg body weight

Arm Description

All infants < 1 year of age with congenital heart diseases requiring cardiac surgery with cardiopulmonary bypass or any patient who requires surgery involving the aorta or the aortic valve will receive both Cefazolin and Vancomycin as preoperative prophylaxis against Surgical Site Infections. This has been recommended in recently published guidelines but not evaluated in children. Intervention: Cefazolin 25 mg/kg body weight and Vancomycin hydrochloride 15 mg/kg body weight

All infants less than one year of age with congenital heart diseases requiring cardiac surgery with cardiopulmonary bypass or all patients who required surgery involving the aorta or the aortic valve received cefazolin 30 mg/kg body weight as preoperative prophylaxis against surgical site infections

Outcomes

Primary Outcome Measures

Number of Patients Who Receive Preoperative Vancomycin and Cefazolin Who Develop a Surgical Site Infection Compared to Those Whose Received Only Cefazolin.
Number of patients who receive preoperative vancomycin and cefazolin who develop a surgical site infection (SSI) compared to those whose received only cefazolin. Surveillance was done with standard procedures and definitions.

Secondary Outcome Measures

Cefazolin Pharmacokinetics
Cefazolin Pharmacokinetics was measured as Central Volume, Peripheral Volume (Fast), Peripheral Volume (Slow)
Cefazolin Pharmacokinetics
Measured as Elimination Clearance Inter-tissue Clearance (Fast) Inter-tissue Clearance(Slow)
Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children During the Peri-operative Period in Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass (CPB)
Vancomycin pharmacokinetics measured as Central Volume, Peripheral Volume (Fast), Peripheral Volume (Slow)
Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children on Cardiopulmonary Bypass (CPB)
Vancomycin pharmacokinetics measured as Elimination Clearance, Inter-tissue Clearance (Fast), Inter-tissue Clearance (Slow).
Count of Participants Experiencing Adverse Events Commonly Associated With Peri-operative Vancomycin Prophylaxis
Will evaluate for vancomycin associated pre or intraoperative adverse events: Hypotension requiring treatment Rash, flushing or Red Man's syndrome Other changes in vital signs (decrease in baseline 02 sat, increased heart or respiratory rate, elevated body temperature) felt to be associated with vancomycin administration An event associated with vancomycin administration which results in delay in surgery

Full Information

First Posted
March 2, 2012
Last Updated
April 16, 2018
Sponsor
Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT01619982
Brief Title
Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
Official Title
Effect of Pre-operative Prophylaxis With Vancomycin on Rate of Cefazolin Non-susceptible Gram Positive Surgical Site Infections in Cardiovascular Surgery Patients
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The investigators hope to learn 1) if the addition of prophylaxis with vancomycin will decrease the rate of cefazolin non-susceptible surgical site infections (SSI), in high risk population 2) to develop better understanding of vancomycin and cefazolin pharmacokinetics in children undergoing cardiopulmonary bypass (CPB) 3) to assess the barriers to vancomycin dosing peri-operatively 4) to assess side effects and risks associated with peri-operative vancomycin administration. This will allow us to improve patient care by better understanding the benefits or the risks of peri-operative vancomycin administration and potentially decrease cefazolin-resistant surgical site infections. In addition, this study gives us the opportunity to evaluate cefazolin and vancomycin pharmacokinetics (pK) on children on CPB. The investigators will take blood samples from 20 patients. In 10 patients the investigators will do Cefazolin pK analysis and in the other 10 the investigators will do pK Vancomycin analysis. For the remainder of 292 patients, only prospective chart review will be done to determine the incidence of SSIs. This data will be compared with 936 controls who received only Cefazolin pre-operatively as prophylaxis for SSI's. --------------------------------------------------------------------------------
Detailed Description
With 100% compliance with the surgical infection prevention (SIP) bundle, the risk of surgical site infections (SSIs) has decreased considerably, but is still greater than the baseline rate at the best comparison hospital (2.5%). Recent analysis of SSI's in cardiovascular surgery patients identified more than half being caused by cefazolin resistant gram positive bacteria (methicillin resistant coagulase negative staphylococci- MRSE (methicillin resistant Staphylococcus epidermidis, or methicillin resistant Staphylococcus aureus- MRSA). Cefazolin is routinely given pre-operatively as surgical prophylaxis in patients undergoing cardiovascular surgery. Vancomycin is not routinely recommended for prophylaxis due to concerns of developing vancomycin resistance, however patients with MRSE and MRSA SSIs end up needing additional surgery to remove or replace infected hardware or grafts and/or additional weeks to months of intravenous vancomycin therapy. This results in significant morbidity to the children and cost to the institution. Several published guidelines suggest the use of pre-operative prophylaxis with vancomycin (alone or in conjunction with cefazolin) in instances where patients may be at higher risk for infection with MRSE or MRSA. The purpose of this study is to determine whether the addition of vancomycin to standard pre-operative prophylaxis with cefazolin in selected high risk subjects along with the full SIP bundle will decrease the incidence of cefazolin-resistant SSI's.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Heart Diseases, Aortic Valve Disorder

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cefazolin 25 mg/kg body weight and vancomycin
Arm Type
Active Comparator
Arm Description
All infants < 1 year of age with congenital heart diseases requiring cardiac surgery with cardiopulmonary bypass or any patient who requires surgery involving the aorta or the aortic valve will receive both Cefazolin and Vancomycin as preoperative prophylaxis against Surgical Site Infections. This has been recommended in recently published guidelines but not evaluated in children. Intervention: Cefazolin 25 mg/kg body weight and Vancomycin hydrochloride 15 mg/kg body weight
Arm Title
Cefazolin only 30mg/kg body weight
Arm Type
Other
Arm Description
All infants less than one year of age with congenital heart diseases requiring cardiac surgery with cardiopulmonary bypass or all patients who required surgery involving the aorta or the aortic valve received cefazolin 30 mg/kg body weight as preoperative prophylaxis against surgical site infections
Intervention Type
Drug
Intervention Name(s)
Cefazolin 25 mg/kg body weight and Vancomycin hydrochloride
Other Intervention Name(s)
Cefazolin: Brand Names Ancef, Vancomycin HCL: Brand name Vancocin
Intervention Description
Cefazolin 25 mg/kg/dose administered intravenously over 5 minutes within 60 minutes of surgical incision and then re-dosed (25 mg/kg: maximum 2 grams/dose) every 4 hours intra-operatively depending on the duration of surgery as per standard peri-operative prophylaxis for cardiac surgery and Vancomycin 15 mg/kg (max 1.5 gram/dose) will be administered intravenously over 1-2 hours (after completion of cefazolin infusion) For patients younger than 1 month of age, a one-time repeat dose of 15 mg/kg can be given intraoperatively 12 hours after the beginning of the first vancomycin dose if the procedure is > 12 hours in duration. For patients equal to or older than 1 month, a one-time repeat dose of 15 mg/kg (max 1.5 grams) will be given intra-operatively 8 hours after the beginning of the first vancomycin dose if the procedure is > 8 hours in duration.
Intervention Type
Drug
Intervention Name(s)
Cefazolin 30 mg/kg body weight
Other Intervention Name(s)
Cefazolin: Brand Names Ancef, Kefzol
Intervention Description
Intervention: Drug: Cefazolin pre-operative prophylaxis Other Names: Cefazolin: Brand Names Ancef, Kefzol Cefazolin 30 mg/kg/dose administered intravenously over 10 minutes within 60 minutes of surgical incision and then re-dosed (30 mg/kg: maximum 2 grams/dose) every 4 hours intra-operatively depending on the duration of surgery as per standard peri-operative prophylaxis for cardiac surgery.
Primary Outcome Measure Information:
Title
Number of Patients Who Receive Preoperative Vancomycin and Cefazolin Who Develop a Surgical Site Infection Compared to Those Whose Received Only Cefazolin.
Description
Number of patients who receive preoperative vancomycin and cefazolin who develop a surgical site infection (SSI) compared to those whose received only cefazolin. Surveillance was done with standard procedures and definitions.
Time Frame
Patients will be monitored for superficial SSIs for 30 days from the date of surgery. Patients will be monitored for 30 days for deep SSIs if no foreign material was implanted and for 1 year if foreign material is present.
Secondary Outcome Measure Information:
Title
Cefazolin Pharmacokinetics
Description
Cefazolin Pharmacokinetics was measured as Central Volume, Peripheral Volume (Fast), Peripheral Volume (Slow)
Time Frame
Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
Title
Cefazolin Pharmacokinetics
Description
Measured as Elimination Clearance Inter-tissue Clearance (Fast) Inter-tissue Clearance(Slow)
Time Frame
Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
Title
Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children During the Peri-operative Period in Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass (CPB)
Description
Vancomycin pharmacokinetics measured as Central Volume, Peripheral Volume (Fast), Peripheral Volume (Slow)
Time Frame
Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
Title
Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children on Cardiopulmonary Bypass (CPB)
Description
Vancomycin pharmacokinetics measured as Elimination Clearance, Inter-tissue Clearance (Fast), Inter-tissue Clearance (Slow).
Time Frame
Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
Title
Count of Participants Experiencing Adverse Events Commonly Associated With Peri-operative Vancomycin Prophylaxis
Description
Will evaluate for vancomycin associated pre or intraoperative adverse events: Hypotension requiring treatment Rash, flushing or Red Man's syndrome Other changes in vital signs (decrease in baseline 02 sat, increased heart or respiratory rate, elevated body temperature) felt to be associated with vancomycin administration An event associated with vancomycin administration which results in delay in surgery
Time Frame
Adverse events to vancomycin will be assessed on each patient in the study during the time the patient is in the operating room (0-<24 hours)

10. Eligibility

Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient less than or equal to 1 year of age who is undergoing cardiovascular surgery requiring CPB or patient under 18 years of age undergoing procedures involving aortic valve or aorta Patients with a positive MRSA screen or a history of MRSA infections who are undergoing any cardiac surgery Exclusion Criteria: Patients who have known hypersensitivity to vancomycin or cephalosporins Patients with renal insufficiency Patients who have received vancomycin or cephalosporins 48 hours prior to the day of surgery Patients whose surgery is due to an infection-related diagnosis such as endocarditis Patients whose parents do not wish to have them receive vancomycin prophylaxis Neonates born at less than 38 weeks gestational age
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathleen Gutierrez, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lucile Packard Children's Hospital at Stanford
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
10219875
Citation
Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol. 1999 Apr;20(4):250-78; quiz 279-80. doi: 10.1086/501620. No abstract available.
Results Reference
background
PubMed Identifier
30995208
Citation
Ingrande J, Gutierrez K, Lemmens HJ, Verma A, Nicolau DP, Sutherland CA, Ramamoorthy C. Pharmacokinetics of Cefazolin and Vancomycin in Infants Undergoing Open-Heart Surgery With Cardiopulmonary Bypass. Anesth Analg. 2019 May;128(5):935-943. doi: 10.1213/ANE.0000000000003876.
Results Reference
derived

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Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients

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