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

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ClinicalTrials.gov Identifier: NCT01619982
Recruitment Status : Completed
First Posted : June 15, 2012
Results First Posted : January 12, 2018
Last Update Posted : May 16, 2018
Sponsor:
Information provided by (Responsible Party):
Chandra Ramamoorthy, Stanford University

Tracking Information
First Submitted Date  ICMJE March 2, 2012
First Posted Date  ICMJE June 15, 2012
Results First Submitted Date  ICMJE June 21, 2017
Results First Posted Date  ICMJE January 12, 2018
Last Update Posted Date May 16, 2018
Study Start Date  ICMJE February 2012
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
Number of Patients Who Receive Preoperative Vancomycin and Cefazolin Who Develop a Surgical Site Infection Compared to Those Whose Received 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. ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 14, 2012)
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. ]
  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.
Change History Complete list of historical versions of study NCT01619982 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
  • Cefazolin Pharmacokinetics [ Time Frame: Drug levels will be sampled only during the peri-operative time period (0 to 12 hours) ]
    Cefazolin Pharmacokinetics was measured as Central Volume, Peripheral Volume (Fast), Peripheral Volume (Slow)
  • Cefazolin Pharmacokinetics [ Time Frame: Drug levels will be sampled only during the peri-operative time period (0 to 12 hours) ]
    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) [ Time Frame: Drug levels will be sampled only during the peri-operative time period (0 to 12 hours) ]
    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) [ Time Frame: Drug levels will be sampled only during the peri-operative time period (0 to 12 hours) ]
    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 [ 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) ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2012)
  • 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) ]
    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) ]
    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) ]
    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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
Official Title  ICMJE Effect of Pre-operative Prophylaxis With Vancomycin on Rate of Cefazolin Non-susceptible Gram Positive Surgical Site Infections in Cardiovascular Surgery Patients
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.

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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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Congenital Heart Diseases
  • Aortic Valve Disorder
Intervention  ICMJE
  • Drug: Cefazolin 25 mg/kg body weight and Vancomycin hydrochloride
    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.
    Other Names:
    • Cefazolin: Brand Names Ancef
    • Vancomycin HCL: Brand name Vancocin
  • Drug: Cefazolin 30 mg/kg body weight

    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.

    Other Name: Cefazolin: Brand Names Ancef, Kefzol
Study Arms  ICMJE
  • Active Comparator: Cefazolin 25 mg/kg body weight 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.

    Intervention: Cefazolin 25 mg/kg body weight and Vancomycin hydrochloride 15 mg/kg body weight

    Intervention: Drug: Cefazolin 25 mg/kg body weight and Vancomycin hydrochloride
  • Cefazolin only 30mg/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
    Intervention: Drug: Cefazolin 30 mg/kg body weight
Publications * 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.

*   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
Actual Enrollment  ICMJE
 (submitted: February 4, 2016)
32
Original Estimated Enrollment  ICMJE
 (submitted: June 14, 2012)
1248
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
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 NCT01619982
Other Study ID Numbers  ICMJE SU-11112011-8670
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Chandra Ramamoorthy, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kathleen Gutierrez, MD Stanford University
PRS Account Stanford University
Verification Date April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP