Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery

Pharmacokinetics Clinical Trial

Official title:

Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00701636
• Other study ID #: 12903-01
• Secondary ID: IIS 0003-07-2007
• Status: Completed
• Phase: Phase 3
• First received: June 17, 2008
• Last updated: January 4, 2011
• Start date: July 2008
• Est. completion date: October 2010

Study information

• Verified date: January 2011
• Source: Los Angeles Biomedical Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardUnited States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 74 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Pharmacokinetics
• Staphylococcus Aureus
• Surgical Wound Infection
• Wound Infection

Intervention

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.

Locations

Country	Name	City	State
United States	Harbor-UCLA Medical Center	Torrance	California

Sponsors (4)

Lead Sponsor	Collaborator
Los Angeles Biomedical Research Institute	Cubist Pharmaceuticals LLC, Hartford Hospital, Western University of Health Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of daptomycin in plasma		Hospital discharge or 7 days, whichever comes first	Yes