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

NCT01619982 | Completed Phase 4 Results

• 1 other identifier: SU-11112011-8670
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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. \--------------------------------------------------------------------------------

Conditions

Congenital Heart Diseases; Aortic Valve Disorder

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (5)

• Cefazolin Pharmacokinetics

  Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)

• Cefazolin Pharmacokinetics

  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)

  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)

  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

  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)

Study Arms (2)

Cefazolin 25 mg/kg body weight and vancomycin

ACTIVE COMPARATOR

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 only 30mg/kg body weight

OTHER

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

Interventions

Cefazolin 25 mg/kg body weight and Vancomycin hydrochloride DRUG

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.

Also known as: Cefazolin: Brand Names Ancef, Vancomycin HCL: Brand name Vancocin

Cefazolin 25 mg/kg body weight and vancomycin

Cefazolin 30 mg/kg body weight DRUG

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.

Also known as: Cefazolin: Brand Names Ancef, Kefzol

Cefazolin only 30mg/kg body weight

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, 94304, United States

Location

Related Publications (2)

• 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.

  PMID: 10219875 BACKGROUND

• 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.

  PMID: 30995208 DERIVED

MeSH Terms

Conditions

Heart Defects, Congenital; Aortic Valve Disease

Interventions

Cefazolin; Weights and Measures; Vancomycin

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Investigative Techniques; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Chandra Ramamoothy
• Organization: Stanford University

chandrar@stanford.edu

650-723-5728

Study Officials

• Kathleen Gutierrez, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Anesthesiology, Department of Pediatric Cardiac Anesthesia

Study Record Dates

• First Submitted: March 2, 2012
• First Posted: June 15, 2012
• Study Start: February 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 16, 2018
• Results First Posted: January 12, 2018

Record last verified: 2018-04

Locations

US (1)