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Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery

Primary Purpose

Late Effects of Surgery, Staphylococcus Aureus, Surgical Site Infection

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
daptomycin
Sponsored by
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Late Effects of Surgery focused on measuring Daptomycin, Antibiotic Prophylaxis, Pharmacokinetics, Surgical Wound Infection, Staphylococcus aureus, Cardiopulmonary Bypass Surgery

Eligibility Criteria

19 Years - 74 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Harbor-UCLA Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Cases

Controls

Arm Description

The first 15 subjects enrolled will receive the intervention drug daptomycin as surgical antibiotic prophylaxis.

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.

Outcomes

Primary Outcome Measures

Mean Daptomycin Concentrations at 12, 18, 24, and 48 h
Mean daptomycin concentrations (mcg/ml) at 12, 18, 24, and 48 h

Secondary Outcome Measures

Full Information

First Posted
June 17, 2008
Last Updated
July 19, 2016
Sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Collaborators
Cubist Pharmaceuticals LLC, Hartford Hospital, Western University of Health Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT00701636
Brief Title
Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery
Official Title
Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
October 2010 (Actual)
Study Completion Date
October 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Collaborators
Cubist Pharmaceuticals LLC, Hartford Hospital, Western University of Health Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Late Effects of Surgery, Staphylococcus Aureus, Surgical Site Infection
Keywords
Daptomycin, Antibiotic Prophylaxis, Pharmacokinetics, Surgical Wound Infection, Staphylococcus aureus, Cardiopulmonary Bypass Surgery

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cases
Arm Type
Experimental
Arm Description
The first 15 subjects enrolled will receive the intervention drug daptomycin as surgical antibiotic prophylaxis.
Arm Title
Controls
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
daptomycin
Other Intervention Name(s)
Cubicin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Mean Daptomycin Concentrations at 12, 18, 24, and 48 h
Description
Mean daptomycin concentrations (mcg/ml) at 12, 18, 24, and 48 h
Time Frame
Hospital discharge or 7 days, whichever comes first

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility 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/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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Loren G Miller, M.D., M.P.H.
Organizational Affiliation
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Harbor-UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90509
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Data may be shared upon written request to the principal investigator.
Citations:
PubMed Identifier
21444695
Citation
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. Epub 2011 Mar 28.
Results Reference
result
Links:
URL
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101392/
Description
Free full text article

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Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery

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