Dalbavancin as an option for treatment of S. aureus bacteremia (DOTS): study protocol for a phase 2b, multicenter, randomized, open-label clinical trial

Nicholas A. Turner, Division of Infectious Diseases, Duke University School of Medicine, Durham, NC, USA.
Smitha Zaharoff, Duke Clinical Research Institute, Durham, NC, USA.
Heather King, Population Health Sciences and Division of General Internal Medicine, Duke University School of Medicine, Durham, NC, USA.
Scott Evans, The Biostatistics Center and Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Rockville, MD, USA.
Toshimitsu Hamasaki, The Biostatistics Center and Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Rockville, MD, USA.
Thomas Lodise, Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
Varduhi Ghazaryan, Division of Microbiology and Infectious Diseases (DMID), National Institutes of Health (NIH), Bethesda, MD, USA.
Tatiana Beresnev, Division of Microbiology and Infectious Diseases (DMID), National Institutes of Health (NIH), Bethesda, MD, USA.
Todd Riccobene, AbbVie, Madison, NJ, USA.
Rinal Patel, AbbVie, Madison, NJ, USA.
Sarah B. Doernberg, Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Urania Rappo, BiomX, Inc, Branford, CT, USA.
Vance G. Fowler, Division of Infectious Diseases, Duke University School of Medicine, Durham, NC, USA.
Thomas L. Holland, Division of Infectious Diseases, Duke University School of Medicine, Durham, NC, USA. thomas.holland@duke.edu.

Document Type

Journal Article

Publication Date

5-16-2022

Journal

Trials

Volume

23

Issue

1

DOI

10.1186/s13063-022-06370-1

Keywords

Bacteremia; Dalbavancin; Randomized controlled trial; Right-sided endocarditis; Staphylococcus aureus

Abstract

BACKGROUND: Staphylococcus aureus bacteremia is a life-threatening infection and leading cause of infective endocarditis, with mortality rates of 15-50%. Treatment typically requires prolonged administration of parenteral therapy, itself associated with high costs and potential catheter-associated complications. Dalbavancin is a lipoglycopeptide with potent activity against Staphylococcus and a long half-life, making it an appealing potential therapy for S. aureus bacteremia without the need for durable central venous access. METHODS: DOTS is a phase 2b, multicenter, randomized, assessor-blinded, superiority, active-controlled, parallel-group trial. The trial will enroll 200 adults diagnosed with complicated S. aureus bacteremia, including definite or possible right-sided infective endocarditis, who have been treated with effective antibiotic therapy for at least 72 h (maximum 10 days) and with subsequent clearance of bacteremia prior to randomization to study treatment. Subjects will be randomized 1:1 to complete their antibiotic treatment course with either two doses of dalbavancin on days 1 and 8, or with a total of 4-8 weeks of standard intravenous antibiotic therapy. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at day 70 for patients randomized to dalbavancin versus standard of care. Key secondary endpoints include quality of life outcomes and pharmacokinetic analyses of dalbavancin. DISCUSSION: The DOTS trial will establish whether dalbavancin is superior to standard parenteral antibiotic therapy for the completion of treatment of complicated S. aureus bacteremia. TRIAL REGISTRATION: US National Institutes of Health ClinicalTrials.gov NCT04775953 . Registered on 1 March 2021.

Department

Biostatistics and Bioinformatics

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