Endocarditis, Bacterial
Conditions
Keywords
Enterococcus, Daptomycin, Endocarditis
Brief summary
The aim of this study is to determine the safety and efficacy of daptomycin when used as an adjuvant agent to standard care in the treatment of proven native valve Enterococcal endocarditis. Patients with this disease will be offered the option of receiving daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving. The hypothesis of this study is that daptomycin added to standard therapy for Enterococcal endocarditis is safe and efficacious. Patients who receive daptomycin + standard therapy will be compared to patients who receive standard therapy alone with respect to the following outcomes: 1. Safety. 1. The frequency of any Grade 3 or 4 toxicity (DAIDS scale) will be measured. 2. The frequency of muscle toxicity or renal toxicity, as determined by predefined criteria. 2. Efficacy. 1. Clinical efficacy. * Time to clearance of bacteremia * Cure at 6 weeks following completion of antibiotic therapy * Mortality at 6 weeks following completion of antibiotic therapy 2. Microbiologic efficacy. * Peak and trough serum bactericidal titers * The minimum bactericidal concentration of Enterococci to daptomycin We expect to enroll 40 patients over 2 years.
Interventions
DRUGDaptomycin
daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving for native valve enterococcal endocarditis
Sponsors
Weill Medical College of Cornell University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 or over * Definite Enterococcal endocarditis, as defined by modified Duke criteria * Able to complete follow-up 3 and 6 weeks following completion of intravenous antibiotic therapy
Exclusion criteria
* Pregnancy or breast feeding * Creatine phosphokinase levels over two times the upper limit of normal * Renal insufficiency or dialysis requirement. * Presence of chronic indwelling bloodstream catheters or foreign body devices suspected as primary or secondary sites of enterococcal infection unamenable to removal or replacement * Inability to discontinue or abstain from use of a HMG CoA reductase inhibitor during the study period. * Hypersensitivity to any of the study medications. * Any condition that, in the investigator's opinion, may interfere with protocol compliance including, but not limited to, active substance abuse and/or dementia. * Prosthetic valve endocarditis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Grade 3 or 4 Toxicity (DAIDS Scale) | weekly | Number of Participants any Grade 3 or 4 toxicity (DAIDS scale); please see adverse event table for details |
| Number of Participants With Muscle Toxicity or Renal Toxicity, as Determined by Predefined Criteria | weekly | Number of Participants with creatine kinase elevation \> 3x upper limit of normal or elevations of serum Cr \>= 30% above baseline |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adjunctive Daptomycin Group please see study description for study enrollment | 5 |
| Standard of Care Group as per study description | 1 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 |
Baseline characteristics
| Characteristic | Adjunctive Daptomycin Group | Standard of Care Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 0 Participants | 3 Participants |
| Age, Continuous | 69 years | 74 years | 70 years |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 0 / 1 |
| serious Total, serious adverse events | 5 / 5 | 0 / 1 |
Outcome results
Primary
Number of Participants With Any Grade 3 or 4 Toxicity (DAIDS Scale)
Number of Participants any Grade 3 or 4 toxicity (DAIDS scale); please see adverse event table for details
Time frame: weekly
Population: Study terminated due to insufficient enrollment; therefore data not sufficient for planned analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adjunctive Daptomycin Group | Number of Participants With Any Grade 3 or 4 Toxicity (DAIDS Scale) | 4 Participants |
| Standard of Care Group | Number of Participants With Any Grade 3 or 4 Toxicity (DAIDS Scale) | 0 Participants |
Primary
Number of Participants With Muscle Toxicity or Renal Toxicity, as Determined by Predefined Criteria
Number of Participants with creatine kinase elevation \> 3x upper limit of normal or elevations of serum Cr \>= 30% above baseline
Time frame: weekly
Population: study terminated due to inadequate enrollment; therefore data not sufficient for planned analysis
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adjunctive Daptomycin Group | Number of Participants With Muscle Toxicity or Renal Toxicity, as Determined by Predefined Criteria | Elevated serum creatinine >= 30% above baseline | 1 Participants |
| Adjunctive Daptomycin Group | Number of Participants With Muscle Toxicity or Renal Toxicity, as Determined by Predefined Criteria | Elevate serum creatine kinase > 3X ULN | 0 Participants |
| Standard of Care Group | Number of Participants With Muscle Toxicity or Renal Toxicity, as Determined by Predefined Criteria | Elevated serum creatinine >= 30% above baseline | 1 Participants |
| Standard of Care Group | Number of Participants With Muscle Toxicity or Renal Toxicity, as Determined by Predefined Criteria | Elevate serum creatine kinase > 3X ULN | 0 Participants |