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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Kathleen M. Gutierrez, Stanford University
ClinicalTrials.gov Identifier:
NCT01619982
First received: March 2, 2012
Last updated: September 29, 2014
Last verified: September 2014
  Purpose

The investigators hope to learn 1) if the addition of prophylaxis with vancomycin will decrease the rate of cefazolin non-susceptible SSI's, in high risk population 2) to develop better understanding of vancomycin and cefazolin pharmacokinetics in children undergoing cardiopulmonary bypass 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 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 SSI's.

This data will be compared with 936 controls who received only Cefazolin pre-operatively as prophylaxis for SSI's.

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Condition Intervention Phase
Congenital Heart Diseases
Aortic Valve Disorder
Drug: Cefazolin pre-operative prophylaxis
Drug: Vancomycin hydrochloride
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Effect of Pre-operative Prophylaxis With Vancomycin on Rate of Cefazolin Non-susceptible Gram Positive Surgical Site Infections in Cardiovascular Surgery Patients

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Effectiveness of pre-operative vancomycin in prevention of cefazolin resistant surgical site infections in children undergoing cardiovascular surgery involving cardiopulmonary bypass, compared to historical controls receiving only cefazolin [ 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. ] [ Designated as safety issue: Yes ]
    1. Number of patients who receive preoperative vancomycin and cefazolin who develop a surgicial site infection compared to those whose received only cefazolin
    2. Surveillance will be performed per standard infection control definitions and procedures.


Secondary Outcome Measures:
  • Cefazolin pharmacokinetics (Plasma concentration vs time curve) in children during cardiopulmonary bypass (CPB). [ Time Frame: Enrollment anticipated to take 6 months. Drug levels will be sampled only during the peri-operative time period (0 to 12 hours) ] [ Designated as safety issue: No ]

    Will measure:

    1. Cefazolin concentrations prior to and during CPB to determine impact of CPB on:

    1. Serum levels at mulitple time points
    2. AUC
    3. Volume of distribution
    4. Total body clearance.
    5. Elimination half life

  • Vancomycin pharmacokinetics (plasma concentration vs time curve) in children on cardiopulmonary bypass (CPB) [ Time Frame: Enrollment anticipated to take 6 months. Drug levels will be monitored only during the peri-operative period (0-12 hours) ] [ Designated as safety issue: No ]

    Will measure:

    1. Vancomycin levels prior to and during CPB to determine effects of CPB on:

    1. Serum levels at multiple time points
    2. AUC
    3. Volume of distribution
    4. Total body clearance
    5. Elimination half life

  • Evaluation of adverse events associated with peri-operative vancomycin prophylaxis [ 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) ] [ Designated as safety issue: Yes ]

    Will evaluate for vancomycin associated pre or intraoperative adverse events:

    1. Hypotension requiring treatment
    2. Rash, flushing or Red Man's syndrome
    3. 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
    4. An event associated with vancomycin administration which results in delay in surgery


Estimated Enrollment: 1248
Study Start Date: February 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Cefazolin only
Retrospective Comparison: 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 who received cefazolin as preoperative prophylaxis against surgical site infections (for retrospective analysis). The cefazolin dose regimen used for the retrospective case controls is the same as for the patients in the prospective cefazolin plus vancomycin study.
Drug: Cefazolin pre-operative prophylaxis
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.
Other Name: Cefazolin: Brand Names Ancef, Kefzol
Active Comparator: Cefazolin and vancomycin
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.
Drug: Cefazolin pre-operative prophylaxis
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.
Other Name: Cefazolin: Brand Names Ancef, Kefzol
Drug: Vancomycin hydrochloride
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.
Other Names:
  • Vancomycin HCL
  • Vancocin

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, 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.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01619982

Locations
United States, California
Lucile Packard Children's Hospital at Stanford
Palo Alto, California, United States, 94304
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Kathleen Gutierrez, MD Stanford University
  More Information

Publications:
Responsible Party: Kathleen M. Gutierrez, Associate Professor,Med Center Line, Infectious Diseases, Stanford University
ClinicalTrials.gov Identifier: NCT01619982     History of Changes
Other Study ID Numbers: SU-11112011-8670
Study First Received: March 2, 2012
Last Updated: September 29, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Heart Defects, Congenital
Heart Diseases
Heart Valve Diseases
Cardiovascular Abnormalities
Cardiovascular Diseases
Congenital Abnormalities
Cefazolin
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014