Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery

This study has been completed.
Sponsor:
Collaborators:
Cubist Pharmaceuticals
Hartford Hospital
Western University of Health Sciences
Information provided by:
Los Angeles Biomedical Research Institute
ClinicalTrials.gov Identifier:
NCT00701636
First received: June 17, 2008
Last updated: January 4, 2011
Last verified: January 2011
  Purpose

This investigation is a prospective, open-label pharmacokinetic study of daptomycin prophylaxis in patients undergoing coronary artery bypass graft surgery without valvular replacement.


Condition Intervention Phase
Pharmacokinetics
Staphylococcus Aureus
Surgical Wound Infection
Drug: daptomycin
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery

Resource links provided by NLM:


Further study details as provided by Los Angeles Biomedical Research Institute:

Primary Outcome Measures:
  • Concentration of daptomycin in plasma [ Time Frame: Hospital discharge or 7 days, whichever comes first ] [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: July 2008
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cases
The first 15 subjects enrolled will receive the intervention drug daptomycin as surgical antibiotic prophylaxis.
Drug: daptomycin
Subjects enrolled in the intervention group will receive a single intravenous administration of daptomycin 8 mg/kg 30-60 minutes prior to surgery (incision). The 500 mg vial will be reconstituted with 10 mL of 0.9%NS and further diluted in 50 mL of 0.9% NS to be given over a 30 minute infusion.
Other Name: Cubicin
No Intervention: Controls
15 subjects will be enrolled in the standard of care antibiotic group to serve as the controls. Controls will receive no experimental medications or treatments. The purpose of enrolling control patients was to serve as a reference group for intervention patients. Specifically cases and controls will be compared for changes in commonly collected hematologic parameters, creatinine, and CPK. Additionally, parameters collected during anesthesia will be compared. Controls will be matched to the intervention group by age (+/- 10 years), gender, and ethnicity.

Detailed Description:

Cardiothoracic surgery is a commonly performed procedure in the United States. Many sites previously used cefazolin, an antibiotic, as standard prophylaxis to prevent surgical site infections. However, given most bacteria causing surgical site infections are now resistant to cefazolin, most center are using vancomycin, an alternative antibiotic, as surgical antibiotic prophylaxis. However, some patients cannot take vancomycin, and there are no well studied alternatives to vancomycin for surgical prophylaxis. Therefore, we are studying daptomycin, a newer FDA-approved antibiotic, as prophylaxis against surgical site infections among patients undergoing cardiothoracic bypass (CPB) with coronary artery bypass graft surgery (CABG). Our study will not be powered to see if daptomycin is as effective as vancomycin at preventing surgical site infections. Instead, the purpose of this study is to validate that adequate levels of antibiotics are present in patients' blood during cardiothoracic bypass surgery.

Study subjects in the intervention group will be followed from the time of enrollment in the study until their discharge from the hospital, or up to 7 days following administration of daptomycin, whichever comes first.

The first 15 subjects enrolled will receive the intervention drug daptomycin as surgical antibiotic prophylaxis and the following 15 subjects will be enrolled as matched controls and will receive the standard of care surgical prophylaxis per the patient's treating physicians. The controls will undergo monitoring for the same safety outcomes that the patients who received daptomycin will undergo.

Subjects enrolled in the intervention group will receive a single intravenous administration of daptomycin 8 mg/kg 30-60 minutes prior to surgery (incision). Blood samples will be drawn by the Research Coordinator. A total of 85 mL of blood will be collected during the study. A total of 14 blood samples will be collected: 4 samples at the Pre-CPB phase, 4 samples during the CPB procedure, and 6 samples Post-CPB. Total plasma daptomycin concentrations will be determined utilizing standard high-performance liquid chromatography techniques. Plasma concentrations will be compared to the minimum inhibitory concentrations (MIC90) of the common pathogens involved in surgical site infections, specifically Staphylococcus aureus and coagulase negative Staphylococcus.

  Eligibility

Ages Eligible for Study:   19 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Hospitalized patients, awaiting scheduled elective coronary artery bypass graft (CABG) surgery without valve replacement surgery
  • Age > 18 years and < 75 years
  • BMI between 18.5 and 35.0 kg/m2
  • Crcl > 50 ml/min calculated based on Cockcroft Gault equation
  • No known active or suspected infection(s)
  • Ability to complete the informed consent process
  • Negative pregnancy test (for women of childbearing age)

Exclusion Criteria:

  • History of allergic reaction to daptomycin or components of daptomycin
  • Receipt of daptomycin within 7 days prior to the surgery
  • Elevated CPK levels (defined as > 3 times the upper limits of known normal)
  • History of myopathy or complaints consistent with myopathy
  • Current or planned use of mycophenolate mofetil, mycophenolic acid, or tobramycin during the subjects' current hospitalization (all of which are known to interact with daptomycin)
  • Inability to complete the informed consent process because of problems with mental capacity
  • Pregnancy and/or breast feeding
  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: NCT00701636

Locations
United States, California
Harbor-UCLA Medical Center
Torrance, California, United States, 90509
Sponsors and Collaborators
Los Angeles Biomedical Research Institute
Cubist Pharmaceuticals
Hartford Hospital
Western University of Health Sciences
Investigators
Principal Investigator: Loren G Miller, M.D., M.P.H. Los Angeles Biomedical Research Institute
  More Information

No publications provided

Responsible Party: Loren Gregory Miller, M.D., M.P.H., Principal Investigator, Los Angeles Biomedical Research Institute
ClinicalTrials.gov Identifier: NCT00701636     History of Changes
Other Study ID Numbers: 12903-01, IIS 0003-07-2007
Study First Received: June 17, 2008
Last Updated: January 4, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Federal Government

Keywords provided by Los Angeles Biomedical Research Institute:
Daptomycin
Antibiotic Prophylaxis
Pharmacokinetics
Surgical Wound Infection
Staphylococcus aureus
Cardiopulmonary Bypass Surgery

Additional relevant MeSH terms:
Infection
Surgical Wound Infection
Wound Infection
Pathologic Processes
Postoperative Complications
Wounds and Injuries
Daptomycin
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014