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

• ClinicalTrials.gov Identifier: NCT03148756
• Recruitment Status: Terminated
• First Posted: May 11, 2017
• Results First Posted: September 10, 2018
• Last Update Posted: September 10, 2018
• Sponsor: Allergan
• Information provided by (Responsible Party): Allergan

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Endocarditis; Bacteremia	Drug: Dalbavancin; Drug: Standard of Care	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 12, 2017
• Actual Primary Completion Date: August 4, 2017
• Actual Study Completion Date: August 4, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dalbavancin; Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1, and on Day 8.	Drug: Dalbavancin; Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1, and on Day 8.
Active Comparator: Standard of Care; Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks.	Drug: Standard of Care; Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Clinical Response at Day 84 in the Intent-to Treat (ITT) Population [ Time Frame: 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 Outcome Measures :

1. Percentage of Participants With Clinical Outcome of Success at Day 42 in the ITT Population [ Time Frame: 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.
2. Percentage of Participants With Clinical Outcome of Success at Day 42 in the Clinically Evaluable (CE) Population [ Time Frame: 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.
3. Number of Participants With Day 84 Mortality in the Safety Population [ Time Frame: Day 84 ]
   Day 84 mortality was measured by the number of deaths up to Day 84.
4. Percentage of Participants With Clinical Outcome of Success at Day 84 in the CE Population [ Time Frame: 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.
5. Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 42 in the ITT Population [ Time Frame: 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.
6. Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 84 in the ITT Population [ Time Frame: 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.
7. Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 42 in the CE Population [ Time Frame: 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.
8. Percentage of Participants With Clinical Outcome of Success by Pathogen at Day 84 in the CE Population [ Time Frame: 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.
9. Percentage of Participants With Microbiological Success by Pathogen at Day 42 in the ITT Population [ Time Frame: 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.
10. Percentage of Participants With Microbiological Success by Pathogen at Day 84 in the ITT Population [ Time Frame: 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.
11. Percentage of Participants With Microbiological Success by Pathogen at Day 42 in the CE Population [ Time Frame: 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.
12. Percentage of Participants With Microbiological Success by Pathogen at Day 84 in the CE Population [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Florida

Midway Immunology and Research Center

Fort Pierce, Florida, United States, 34982

Sponsors and Collaborators

Allergan

Investigators

• Study Director: Urania Rappo, MD; Allergan

  Study Documents (Full-Text)

Documents provided by Allergan:

Study Protocol and Statistical Analysis Plan  [PDF] October 19, 2016

More Information

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT03148756
• Other Study ID Numbers: DAL-MD-09
• First Posted: May 11, 2017
• Results First Posted: September 10, 2018
• Last Update Posted: September 10, 2018
• Last Verified: August 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Bacteremia; Endocarditis, Bacterial; Endocarditis; Bacterial Infections; Sepsis; Infection; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Cardiovascular Infections; Dalbavancin; Anti-Bacterial Agents; Anti-Infective Agents