Dalbavancin as an option for treatment of S. aureus bacteremia (DOTS): study protocol for a phase 2b, multicenter, randomized, open-label clinical trial.
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Issue Date
5/16/2022
Authors
Turner, Nicholas A
Zaharoff, Smitha
King, Heather
Evans, Scott
Hamasaki, Toshimitsu
Lodise, Thomas
Ghazaryan, Varduhi
Beresnev, Tatiana
Riccobene, Todd
Patel, Rinal
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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.
Citation
Turner NA, Zaharoff S, King H, Evans S, Hamasaki T, Lodise T, Ghazaryan V, Beresnev T, Riccobene T, Patel R, Doernberg SB, Rappo U, Fowler VG Jr, Holland TL; Antibacterial Resistance Leadership Group (ARLG). Dalbavancin as an option for treatment of S. aureus bacteremia (DOTS): study protocol for a phase 2b, multicenter, randomized, open-label clinical trial. Trials. 2022 May 16;23(1):407. doi: 10.1186/s13063-022-06370-1. PMID: 35578360; PMCID: PMC9109297.
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UM1AI104681/National Institute of Allergy and Infectious Diseases