Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery
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| ClinicalTrials.gov Identifier: NCT00701636 |
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Recruitment Status :
Completed
First Posted : June 19, 2008
Results First Posted : August 29, 2016
Last Update Posted : August 29, 2016
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Late Effects of Surgery Staphylococcus Aureus Surgical Site Infection | Drug: daptomycin | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 30 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Prevention |
| Official Title: | Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery |
| Study Start Date : | July 2008 |
| Actual Primary Completion Date : | October 2010 |
| Actual Study Completion Date : | October 2010 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cases
The first 15 subjects enrolled will receive the intervention drug daptomycin as surgical antibiotic prophylaxis.
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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 |
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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.
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- Mean Daptomycin Concentrations at 12, 18, 24, and 48 h [ Time Frame: Hospital discharge or 7 days, whichever comes first ]Mean daptomycin concentrations (mcg/ml) at 12, 18, 24, and 48 h
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| Ages Eligible for Study: | 19 Years to 74 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00701636
| United States, California | |
| Harbor-UCLA Medical Center | |
| Torrance, California, United States, 90509 | |
| Principal Investigator: | Loren G Miller, M.D., M.P.H. | Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center |
Publications of Results:
| Responsible Party: | Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center |
| ClinicalTrials.gov Identifier: | NCT00701636 |
| Other Study ID Numbers: |
12903-01 IIS 0003-07-2007 ( Other Identifier: Cubist Pharmaceuticals ) |
| First Posted: | June 19, 2008 Key Record Dates |
| Results First Posted: | August 29, 2016 |
| Last Update Posted: | August 29, 2016 |
| Last Verified: | July 2016 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Data may be shared upon written request to the principal investigator. |
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Daptomycin Antibiotic Prophylaxis Pharmacokinetics |
Surgical Wound Infection Staphylococcus aureus Cardiopulmonary Bypass Surgery |
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Surgical Wound Infection Infections Wound Infection Postoperative Complications |
Pathologic Processes Daptomycin Anti-Bacterial Agents Anti-Infective Agents |