Clinical trial NCT00701636: Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery
Official title: Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Late Effects of Surgery
Staphylococcus Aureus
Surgical Site Infection
Keywords: Daptomycin
Antibiotic Prophylaxis
Pharmacokinetics
Surgical Wound Infection
Staphylococcus aureus
Cardiopulmonary Bypass Surgery
Lead sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Sponsor class: OTHER
Collaborators: name: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
name: Hartford Hospital
name: Western University of Health Sciences
First posted: 2008-06-19
Enrollment: 30
Sex: ALL
Minimum age (years): 19
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Mean Daptomycin Concentrations at 12, 18, 24, and 48 h
timeFrame: Hospital discharge or 7 days, whichever comes first
Secondary outcomes:
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
Study officials:
affiliation: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
name: Loren G Miller, M.D., M.P.H.
role: PRINCIPAL_INVESTIGATOR
References:
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.