Efficacy and Safety of Dalbavancin Compared to Standard of Care Antibiotic Therapy for the Completion of Treatment of Patients With Complicated Bacteremia or Infective Endocarditis

Study Overview
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Brief Summary
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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.

Official Title
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Phase 2, Open-Label, Randomized, Multicenter Study to Compare the Efficacy and Safety of Dalbavancin to Standard of Care Antibiotic Therapy for the Completion of Treatment of Patients With Complicated Bacteremia or Documented Infective Endocarditis

Conditions
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Endocarditis, Bacteremia

Intervention / Treatment
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* Drug: Dalbavancin
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dalbavancin<br>Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1, and on Day 8. | Drug: Dalbavancin<br>* Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1, and on Day 8.<br>|
| Active Comparator: Standard of Care<br>Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks. | Drug: Standard of Care<br>* Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 42 | 
| 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. | Day 42 | 
| 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. | Day 84 | 
| 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. | Day 84 | 
| 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. | Day 42 | 
| 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. | Day 84 | 
| 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. | Day 42 | 
| 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. | Day 84 | 
| 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. | Day 42 | 
| 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. | Day 84 | 
| 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. | Day 42 | 
| 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. | Day 84 |