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. 2022 May 16;23(1):407.
doi: 10.1186/s13063-022-06370-1.

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  1 , Smitha Zaharoff  2 , Heather King  3   4 , Scott Evans  5 , Toshimitsu Hamasaki  5 , Thomas Lodise  6 , Varduhi Ghazaryan  7 , Tatiana Beresnev  7 , Todd Riccobene  8 , Rinal Patel  8 , Sarah B Doernberg  9 , Urania Rappo  10 , Vance G Fowler Jr  1 , Thomas L Holland  11 ; Antibacterial Resistance Leadership Group (ARLG)
Affiliations

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 et al. Trials. .

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.

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

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Conflict of interest statement

The authors report no competing interests with the work submitted. For full disclosure, the authors report the following outside financial activities: Vance G. Fowler reports receiving consultancy fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, and Roche; grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Basilea, and Janssen; royalties from UptoDate; stock options in Valanbio and ArcBio; and an editorial stipend from the Infectious Diseases Society of America. Thomas L. Holland reports serving on the scientific advisory board for Motif Bio, consulting for Basilea, Motif Bio, Genentech, and Theravance. Heather King reports receiving consultancy feeds from Merck.

Figures

Fig. 1
Fig. 1
Study Schema
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