Bacteremia
Conditions
Keywords
Bacteremia, Staphylococcus aureus
Brief summary
This is a multicenter, randomized, open-label, noninferiority trial of telavancin versus standard IV therapy control (e.g., vancomycin, daptomycin, anti-staphylococcal penicillin (PCN), or cefazolin) in the treatment of subjects with complicated Staphylococcus aureus (S. aureus) bacteremia and SA right-sided infective endocarditis (SA-RIE).
Interventions
Sponsors
Cumberland Pharmaceuticals
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 with at least one blood culture positive for S. aureus within 48 hours before randomization * At least one of the following signs or symptoms of bacteremia: * Temperature ≥ 38.0°C * White blood cell (WBC) count \> 10,000 or \< 4,000 cells/µL or \> 10% immature neutrophils (bands) * Tachycardia (heart rate \> 90 bpm) * Tachypnea (respiratory rate \> 20 breaths/min) * Hypotension (systolic blood pressure \< 90 mmHg) * Signs or symptoms of localized catheter-related infection * At enrollment, subjects must have either 1) known right-sided infective endocarditis by Modified Duke's criteria 2) known complicated bacteremia, demonstrated as signs or symptoms of metastatic foci of S. aureus infection or 3) at least one risk factor for complicated bacteremia.
Exclusion criteria
* Treatment with any potentially effective (anti-staphylococcal) systemic antibiotic for more than 60 hours within 7 days before randomization. EXCEPTION: Documented resistance to the prior systemic antibacterial therapy * Presence of an infection source that will not be managed or controlled within the first 3 days of study drug treatment * Presence of prosthetic cardiac valve or cardiac device (eg, implantable cardioverter defibrillator \[ICD\]), permanent pacemaker, or cardiac valve support ring) * Known or suspected left-sided infective endocarditis (LIE), by Modified Duke Criteria. NOTE: Right-sided infective endocarditis (RIE) is permitted * Known or suspected osteomyelitis or meningitis. NOTE: Evidence of metastatic complications related to the primary infection such as right-sided endocarditis, septic arthritis, septic pulmonary emboli are permitted. S. aureus pneumonia is permitted * Confirmed evidence (identification or gram stain) of a mixed polymicrobial infection with a Gram-negative pathogen that requires non-study antibiotic treatment with agent(s) that have activity against Gram-negative pathogens
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) | Up to 8 weeks | The efficacy endpoint of clinical outcome of cure at the test of cure (TOC) was determined by subjects who meet all of the following criteria, as determined by the investigator and adjudicated by the blinded independent efficacy adjudication committee (IEAC). 1. Alive at TOC 2. Resolution of all clinical signed and symptoms of the Staphylococcus aureus (S. aureus) infection at TOC 3. No evidence of microbiological persistence of relapse 4. No new foci of metastatic S. aureus infection after Day 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population | Up to 8 weeks | The efficacy endpoint of Investigator clinical outcome of cure at the test of cure (TOC) was determined by the following criteria: 1. Subject alive at TOC 2. Resolution of all clinical signs and symptoms of the S. aureus infection at TOC (unless explained by a more likely alternative diagnosis) 3. No evidence of microbiological persistence or relapse 4. No new foci of metastatic S. aureus infection after Day 8 |
| Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population | Up to 8 weeks | This efficacy endpoint was determined to be a clinical failure if the subject switched study antibiotic due to lack of clinical response |
| Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations | Day 8 | After Day 8, any sign or symptom leading to a subsequent confirmed diagnosis of a new metastatic foci of S. aureus infection |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Telavancin 7.5 mg/kg administered intravenously once every 24 hours daily over 60 minutes
Telavancin | 57 |
| Standard of Care Vancomycin, Daptomycin, synthetic penicillin or Cefazolin
Vancomycin
Daptomycin
Synthetic penicillin
Cefazolin | 60 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 5 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Not Specified in report | 3 | 4 |
| Overall Study | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | Standard of Care | Total | Telavancin |
|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 16.33 | 54.5 years STANDARD_DEVIATION 16.44 | 52.3 years STANDARD_DEVIATION 16.41 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants | 39 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 78 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 6 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 13 Participants | 8 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 48 Participants | 92 Participants | 44 Participants |
| Sex: Female, Male Female | 17 Participants | 35 Participants | 18 Participants |
| Sex: Female, Male Male | 43 Participants | 82 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 58 | 5 / 60 |
| other Total, other adverse events | 29 / 58 | 25 / 60 |
| serious Total, serious adverse events | 16 / 58 | 13 / 60 |
Outcome results
Primary
Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC)
The efficacy endpoint of clinical outcome of cure at the test of cure (TOC) was determined by subjects who meet all of the following criteria, as determined by the investigator and adjudicated by the blinded independent efficacy adjudication committee (IEAC). 1. Alive at TOC 2. Resolution of all clinical signed and symptoms of the Staphylococcus aureus (S. aureus) infection at TOC 3. No evidence of microbiological persistence of relapse 4. No new foci of metastatic S. aureus infection after Day 8
Time frame: Up to 8 weeks
Population: One subject enrolled was excluded from all summaries and analyses because the subject was randomized to a higher dose of telavancin (10mg/kg) that the remainder of the subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Telavancin | Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) | Cure | 22 Participants |
| Telavancin | Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) | Failure | 19 Participants |
| Telavancin | Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) | Indeterminate | 6 Participants |
| Standard of Care | Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) | Cure | 27 Participants |
| Standard of Care | Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) | Failure | 21 Participants |
| Standard of Care | Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) | Indeterminate | 4 Participants |
Secondary
Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population
This efficacy endpoint was determined to be a clinical failure if the subject switched study antibiotic due to lack of clinical response
Time frame: Up to 8 weeks
Population: One subject enrolled was excluded from all summaries and analyses because the subject was randomized to a higher dose of telavancin (10mg/kg) that the remainder of the subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Telavancin | Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population | Success | 28 Participants |
| Telavancin | Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population | Failure | 13 Participants |
| Telavancin | Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population | Indeterminate | 5 Participants |
| Telavancin | Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population | Missing | 1 Participants |
| Standard of Care | Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population | Missing | 1 Participants |
| Standard of Care | Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population | Success | 36 Participants |
| Standard of Care | Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population | Indeterminate | 0 Participants |
| Standard of Care | Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population | Failure | 15 Participants |
Secondary
Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population
The efficacy endpoint of Investigator clinical outcome of cure at the test of cure (TOC) was determined by the following criteria: 1. Subject alive at TOC 2. Resolution of all clinical signs and symptoms of the S. aureus infection at TOC (unless explained by a more likely alternative diagnosis) 3. No evidence of microbiological persistence or relapse 4. No new foci of metastatic S. aureus infection after Day 8
Time frame: Up to 8 weeks
Population: One subject enrolled was excluded from all summaries and analyses because the subject was randomized to a higher dose of telavancin (10mg/kg) that the remainder of the subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Telavancin | Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population | Cure | 26 Participants |
| Telavancin | Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population | Failure | 15 Participants |
| Telavancin | Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population | Indeterminate | 3 Participants |
| Telavancin | Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population | Missing | 3 Participants |
| Standard of Care | Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population | Missing | 2 Participants |
| Standard of Care | Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population | Cure | 31 Participants |
| Standard of Care | Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population | Indeterminate | 0 Participants |
| Standard of Care | Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population | Failure | 19 Participants |
Secondary
Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations
After Day 8, any sign or symptom leading to a subsequent confirmed diagnosis of a new metastatic foci of S. aureus infection
Time frame: Day 8
Population: One subject enrolled was excluded from all summaries and analyses because the subject was randomized to a higher dose of telavancin (10mg/kg) that the remainder of the subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Telavancin | Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations | No | 32 Participants |
| Telavancin | Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations | Yes | 6 Participants |
| Telavancin | Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations | Indeterminate | 9 Participants |
| Standard of Care | Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations | Yes | 3 Participants |
| Standard of Care | Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations | No | 41 Participants |
| Standard of Care | Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations | Indeterminate | 8 Participants |