Bacteremia
Conditions
Keywords
Methicillin-resistant, Staphylococcus aureus
Brief summary
There is an increased failure rate for the treatment of Staphylococcus Aureus Bacteremia (SAB) with traditional doses of vancomycin, the standard of care for patients with MRSA bacteremia over the last 40 years. This has been largely attributed to isolates with increased resistance to vancomycin (increased MIC). Daptomycin is an antibiotic that was approved several years ago for the treatment of SAB and is being increasingly used for MRSA bacteremia due to isolates with increased MIC. Increased doses have been recommended for both of these drugs in the treatment of this infection without a trial demonstrating their relative efficacy or safety at higher doses. This study will randomize patients with SAB due to MRSA with an increased MIC to determine the relative efficacy and safety of vancomycin and daptomycin used at higher than traditional doses.
Interventions
DRUGVancomycin
Vancomycin dosed to achieve a trough of 15-20 microgram/mL.
DRUGDaptomycin
Sponsors
Henry Ford Health System
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
St. John Health System, Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * Signed informed consent * All cases of suspected MRSA bacteremia as determined by a patient with at least one blood culture growing gram-positive cocci in clusters with a clinical syndrome consistent with true bacteremia including fever, hypothermia (temperature \< 36.0º C), tachycardia (heart rate \> 100 beats/minute), hypotension (systolic blood pressure \< 90 mm Hg) or other clinical features of sepsis. * All cases of right-sided native valve endocarditis due to MRSA * Patients who are diagnosed with left-sided native valve endocarditis after randomization will be continued in the study * Patients with MRSA bacteremia associated with infected foreign bodies, including vascular prostheses, orthopedic prostheses
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Success at Test of Cure Visit. | 30-42 days post-treatment | Clinical success is the absence of treatment failures. Treatment failures will include death, clinical failure, microbiologic failure, or an adverse event requiring a change in therapy or discontinuation in therapy. |
Secondary
| Measure | Time frame |
|---|---|
| Adverse Event Rate in Each Arm, Including the Nephrotoxicity and Skeletal Muscle Toxicity | 30-42 days post-treatment |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Dose Vancomycin Vancomycin vs. daptomycin: Vancomycin dosed to achieve a trough of 15-20 microgram/mL vs. daptomycin dosed at 8 mg/kg/daily (every 48 hours in end-stage renal disease) | 6 |
| High-dose Daptomycin Vancomycin vs. daptomycin: Vancomycin dosed to achieve a trough of 15-20 microgram/mL vs. daptomycin dosed at 8 mg/kg/daily (every 48 hours in end-stage renal disease) | 5 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 0 | 1 |
Baseline characteristics
| Characteristic | High Dose Vancomycin | High-dose Daptomycin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 4 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 1 Participants | 5 Participants |
| Age, Continuous | 61.8 years STANDARD_DEVIATION 22.6 | 68.2 years STANDARD_DEVIATION 10.2 | 64.7 years STANDARD_DEVIATION 17.5 |
| Region of Enrollment United States | 6 participants | 5 participants | 11 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 1 / 5 |
| serious Total, serious adverse events | 1 / 6 | 0 / 5 |
Outcome results
Primary
Number of Participants With Clinical Success at Test of Cure Visit.
Clinical success is the absence of treatment failures. Treatment failures will include death, clinical failure, microbiologic failure, or an adverse event requiring a change in therapy or discontinuation in therapy.
Time frame: 30-42 days post-treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose Vancomycin | Number of Participants With Clinical Success at Test of Cure Visit. | 4 participants |
| High-dose Daptomycin | Number of Participants With Clinical Success at Test of Cure Visit. | 3 participants |
Secondary
Adverse Event Rate in Each Arm, Including the Nephrotoxicity and Skeletal Muscle Toxicity
Time frame: 30-42 days post-treatment