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Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery

This study has been completed.
Sponsor:
Collaborators:
Cubist Pharmaceuticals LLC
Hartford Hospital
Western University of Health Sciences
Information provided by (Responsible Party):
Los Angeles Biomedical Research Institute
ClinicalTrials.gov Identifier:
NCT00701636
First received: June 17, 2008
Last updated: July 19, 2016
Last verified: July 2016

June 17, 2008
July 19, 2016
July 2008
October 2010   (final data collection date for primary outcome measure)
Mean Daptomycin Concentrations at 12, 18, 24, and 48 h [ Time Frame: Hospital discharge or 7 days, whichever comes first ] [ Designated as safety issue: Yes ]
Mean daptomycin concentrations (mcg/ml) at 12, 18, 24, and 48 h
Concentration of daptomycin in plasma [ Time Frame: Hospital discharge or 7 days, whichever comes first ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00701636 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery
Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery
This investigation is a prospective, open-label pharmacokinetic study of daptomycin prophylaxis in patients undergoing coronary artery bypass graft surgery without valvular replacement.

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 United States Food and Drug Administration (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 milligram (mg)/kilogram (kg) 30-60 minutes prior to surgery (incision). Blood samples will be drawn by the Research Coordinator. A total of 85 (milliliters) 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.

Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
  • Late Effects of Surgery
  • Staphylococcus Aureus
  • Surgical Site Infection
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% normal saline (NS) and further diluted in 50 mL of 0.9% NS to be given over a 30 minute infusion.
Other Name: Cubicin
  • Experimental: Cases
    The first 15 subjects enrolled will receive the intervention drug daptomycin as surgical antibiotic prophylaxis.
    Intervention: Drug: daptomycin
  • 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.
Nguyen MH, Eells SJ, Tan J, Sheth CT, Omari B, Flores M, Wang J, Miller LG. Prospective, open-label investigation of the pharmacokinetics of daptomycin during cardiopulmonary bypass surgery. Antimicrob Agents Chemother. 2011 Jun;55(6):2499-505. doi: 10.1128/AAC.01404-10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
October 2010
October 2010   (final data collection date for primary outcome measure)

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/meters-squared
  • Crcl > 50 ml/minute 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
Both
19 Years to 74 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00701636
12903-01, IIS 0003-07-2007
Yes
Yes
Data may be shared upon written request to the principal investigator.
Los Angeles Biomedical Research Institute
Los Angeles Biomedical Research Institute
  • Cubist Pharmaceuticals LLC
  • Hartford Hospital
  • Western University of Health Sciences
Principal Investigator: Loren G Miller, M.D., M.P.H. Los Angeles Biomedical Research Institute
Los Angeles Biomedical Research Institute
July 2016

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