Bacteremia, Endocarditis
Conditions
Brief summary
This study will compare dalbavancin to standard of care (SOC) antibiotic therapy for the completion of therapy in patients with complicated bacteremia or infective endocarditis.
Interventions
DRUGDalbavancin
Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1, and on Day 8.
DRUGStandard of Care
Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks.
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A diagnosis of complicated bacteremia or infective endocarditis * Gram-positive bacteremia at screening with methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) or Streptococci * Treatment with standard of care antibiotics for 72 hours (h) - 10 days * Defervescence for at least 24h and clearance of bacteremia from screening pathogen.
Exclusion criteria
* Embolic events * History of prosthetic valve surgery, cardiac device or prosthetic joint * Left-sided endocarditis due to Staphylococcus aureus (S. aureus) * Large mobile vegetations (\>10 mm) on mitral valves * Perivalvular abscess * Uncomplicated bacteremia due to S. aureus * Gram-negative bacteria or fungi in blood cultures * Heart failure associated with infective endocarditis \[Left Ventricular Ejection Fraction (LVEF) \<40%\] * Intravascular material or removable infection source not intended to be removed within 4 days postrandomization * Planned valve replacement surgery within 3 days of randomization * Refractory shock, significant hepatic insufficiency or severe leukopenia \[Absolute Neutrophil Count (ANC) \< 500 cells/mm\^3\] * Known osteomyelitis * Hypersensitivity to dalbavancin or other drugs in glycopeptide class * Infection with enterococci, coagulase-negative staphylococci, or with organism not susceptible to dalbavancin or vancomycin * Immunosuppression/immune deficiency * Concomitant systemic antibacterial therapy for gram-positive infection other than that allowed in protocol * Pregnant or nursing females.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Response at Day 84 in the Intent-to Treat (ITT) Population | Day 84 | Clinical response was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required. Failure was defined as: ongoing signs and symptoms considered by the investigator to be related to complicated bacteremia or IE requiring additional antibacterial therapy or unplanned valve replacement, recurrent bacteremia, death during the study period up to Day 84 or discontinuation of the study medication due to an adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Outcome of Success at Day 42 in the Clinically Evaluable (CE) Population | Day 42 | Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required. |
| Number of Participants With Day 84 Mortality in the Safety Population | Day 84 | Day 84 mortality was measured by the number of deaths up to Day 84. |
| Percentage of Participants With Clinical Outcome of Success at Day 84 in the CE Population | Day 84 | Clinical outcome was either success or failure/relapse. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required. |
| Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 42 in the ITT Population | Day 42 | Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required. |
| Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 84 in the ITT Population | Day 84 | Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required. |
| Percentage of Participants With Clinical Outcome of Success at Day 42 in the ITT Population | Day 42 | Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required. |
| Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 84 in the CE Population | Day 84 | Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required. |
| Percentage of Participants With Microbiological Success by Pathogen at Day 42 in the ITT Population | Day 42 | Microbiological outcome could be either microbiologic success or microbiologic failure. Microbiologic Success was defined as no further growth of baseline pathogen from blood cultures. |
| Percentage of Participants With Microbiological Success by Pathogen at Day 84 in the ITT Population | Day 84 | Microbiological outcome could be either microbiologic success or microbiologic failure. Microbiologic Success was defined as no further growth of baseline pathogen from blood cultures. |
| Percentage of Participants With Microbiological Success by Pathogen at Day 42 in the CE Population | Day 42 | Microbiological outcome could be either microbiologic success or microbiologic failure. Microbiologic Success was defined as no further growth of baseline pathogen from blood cultures. |
| Percentage of Participants With Microbiological Success by Pathogen at Day 84 in the CE Population | Day 84 | Microbiological outcome could be either microbiologic success or microbiologic failure. Microbiologic Success was defined as no further growth of baseline pathogen from blood cultures. |
| Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 42 in the CE Population | Day 42 | Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dalbavancin Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1, and on Day 8. | 0 |
| Standard of Care Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks. | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study Terminated | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Dalbavancin | Standard of Care |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — | — |
| Age, Categorical >=65 years | 0 Participants | — | — |
| Age, Categorical Between 18 and 65 years | 0 Participants | — | — |
| Race/Ethnicity, Customized White | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | — | — |
| Sex: Female, Male Male | 0 Participants | — | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 2 |
| other Total, other adverse events | 0 / 0 | 1 / 2 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Participants With Clinical Response at Day 84 in the Intent-to Treat (ITT) Population
Clinical response was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required. Failure was defined as: ongoing signs and symptoms considered by the investigator to be related to complicated bacteremia or IE requiring additional antibacterial therapy or unplanned valve replacement, recurrent bacteremia, death during the study period up to Day 84 or discontinuation of the study medication due to an adverse event.
Time frame: Day 84
Population: ITT Population included all randomized participants regardless of whether or not study treatment was received. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have an early termination visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard of Care | Number of Participants With Clinical Response at Day 84 in the Intent-to Treat (ITT) Population | Success | 1 Participants |
| Standard of Care | Number of Participants With Clinical Response at Day 84 in the Intent-to Treat (ITT) Population | Failure | 0 Participants |
Secondary
Number of Participants With Day 84 Mortality in the Safety Population
Day 84 mortality was measured by the number of deaths up to Day 84.
Time frame: Day 84
Population: Safety Population included all randomized participants who received at least 1 dose of study treatment. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have an early termination visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care | Number of Participants With Day 84 Mortality in the Safety Population | 0 Participants |
Secondary
Percentage of Participants With Clinical Outcome of Success at Day 42 in the Clinically Evaluable (CE) Population
Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
Time frame: Day 42
Population: CE Population included all participants in the mITT Population (all in the ITT who received ≥1 dose of study treatment) who met criteria for clinical evaluability. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have a termination visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | Percentage of Participants With Clinical Outcome of Success at Day 42 in the Clinically Evaluable (CE) Population | 100 percentage of participants |
Secondary
Percentage of Participants With Clinical Outcome of Success at Day 42 in the ITT Population
Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
Time frame: Day 42
Population: ITT Population included all randomized participants regardless of whether or not study treatment was received. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have an early termination visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | Percentage of Participants With Clinical Outcome of Success at Day 42 in the ITT Population | 100 percentage of participants |
Secondary
Percentage of Participants With Clinical Outcome of Success at Day 84 in the CE Population
Clinical outcome was either success or failure/relapse. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
Time frame: Day 84
Population: CE Population included all participants in the mITT Population (all in the ITT who received ≥1 dose of study treatment) who met criteria for clinical evaluability. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have a termination visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | Percentage of Participants With Clinical Outcome of Success at Day 84 in the CE Population | 100 percentage of participants |
Secondary
Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 42 in the CE Population
Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
Time frame: Day 42
Population: CE Population included all participants in the mITT Population (all in the ITT who received ≥1 dose of study treatment) who met criteria for clinical evaluability. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have a termination visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 42 in the CE Population | 100 percentage of participants |
Secondary
Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 42 in the ITT Population
Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
Time frame: Day 42
Population: ITT Population included all randomized participants regardless of whether or not study treatment was received. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have an early termination visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 42 in the ITT Population | 100 percentage of participants |
Secondary
Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 84 in the CE Population
Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
Time frame: Day 84
Population: CE Population included all participants in the mITT Population (all in the ITT who received ≥1 dose of study treatment) who met criteria for clinical evaluability. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have a termination visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 84 in the CE Population | 100 percentage of participants |
Secondary
Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 84 in the ITT Population
Clinical outcome was either success or failure. Success was defined as resolution of clinical signs and symptoms of complicated bacteremia or infective endocarditis (IE) such that no additional antibiotic therapy was required.
Time frame: Day 84
Population: ITT Population included all randomized participants regardless of whether or not study treatment was received. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have an early termination visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 84 in the ITT Population | 100 percentage of participants |
Secondary
Percentage of Participants With Microbiological Success by Pathogen at Day 42 in the CE Population
Microbiological outcome could be either microbiologic success or microbiologic failure. Microbiologic Success was defined as no further growth of baseline pathogen from blood cultures.
Time frame: Day 42
Population: CE Population included all participants in the mITT Population (all in the ITT who received ≥1 dose of study treatment) who met criteria for clinical evaluability. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have a termination visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | Percentage of Participants With Microbiological Success by Pathogen at Day 42 in the CE Population | 100 percentage of participants |
Secondary
Percentage of Participants With Microbiological Success by Pathogen at Day 42 in the ITT Population
Microbiological outcome could be either microbiologic success or microbiologic failure. Microbiologic Success was defined as no further growth of baseline pathogen from blood cultures.
Time frame: Day 42
Population: ITT Population included all randomized participants regardless of whether or not study treatment was received. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have an early termination visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | Percentage of Participants With Microbiological Success by Pathogen at Day 42 in the ITT Population | 100 percentage of participants |
Secondary
Percentage of Participants With Microbiological Success by Pathogen at Day 84 in the CE Population
Microbiological outcome could be either microbiologic success or microbiologic failure. Microbiologic Success was defined as no further growth of baseline pathogen from blood cultures.
Time frame: Day 84
Population: CE Population included all participants in the mITT Population (all in the ITT who received ≥1 dose of study treatment) who met criteria for clinical evaluability. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have a termination visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | Percentage of Participants With Microbiological Success by Pathogen at Day 84 in the CE Population | 100 percentage of participants |
Secondary
Percentage of Participants With Microbiological Success by Pathogen at Day 84 in the ITT Population
Microbiological outcome could be either microbiologic success or microbiologic failure. Microbiologic Success was defined as no further growth of baseline pathogen from blood cultures.
Time frame: Day 84
Population: ITT Population included all randomized participants regardless of whether or not study treatment was received. No participants were enrolled in the Dalbavancin arm. Due to early termination of the study, 1 participant did not have clinical outcomes determined, but did have an early termination visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard of Care | Percentage of Participants With Microbiological Success by Pathogen at Day 84 in the ITT Population | 100 percentage of participants |