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

April 16, 2018 updated by: Chandra Ramamoorthy, Stanford University

Effect of Pre-operative Prophylaxis With Vancomycin on Rate of Cefazolin Non-susceptible Gram Positive Surgical Site Infections in Cardiovascular Surgery Patients

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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Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

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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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
32

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital at Stanford

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
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
Other: 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
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 Names:
  • Cefazolin: Brand Names Ancef, Kefzol

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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 Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
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)
Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
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)
Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
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).
Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
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
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Stanford University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kathleen Gutierrez, MD, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

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Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 2, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 15, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 16, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 16, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

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  • SU-11112011-8670

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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