Staphylococcal BacteraemiaPhase 2NCT04775953
DOTS: Dalbavancin as an Option for Treatment of Staphylococcus Aureus Bacteremia
A Phase 2 study testing Cefazolin, Dalbavancin and Daptomycin in people with Staphylococcal Bacteraemia, run by National Institute of Allergy and Infectious Diseases (NIAID) at 24 sites in 2 countries.
Trial summary
This is a Phase 2b clinical study, multicenter, randomized, open-label, assessor-blinded, superiority study. The study will compare dalbavancin to standard of care antibiotic therapy for the completion of therapy in patients with complicated bacteremia or right-sided native valve Infective Endocarditis (IE) caused by… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Staphylococcal Bacteraemia
- What is being tested?
- Cefazolin, Dalbavancin and Daptomycin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 24 sitesin 2 countries
- Study dates
- 22 Apr 2021to 1 Dec 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent obtained from the patient or legally authorized representative before the initiation of any study-specific procedures.
- Patients > / = to 18 years old.
- A diagnosis of complicated Staphylococcus aureus (either Methicillin-sensitive Staphylococcus aureus or Methicillin-resistant Staphylococcus aureus) bloodstream infection.
- Treated with effective antibiotic therapy for at least 72 hours (maximum 10 days).*
- Ten consecutive days prior to randomization is the maximum allowed treatment duration. If a subject has received intermittent or incomplete therapy earlier in the treatment course for this episode of S. aureus bacteremia, then discuss with the protocol PI and DMID Medical Officer prior to enrollment.
- Subsequent defervescence for at least 24 hours and clearance of bacteremia from the qualifying pathogen (at Screening), with negative blood culture incubated for at least 48 hours.**
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- Two negative blood cultures incubated for 48 hours are preferred. However, if only a single blood culture set is drawn, no growth at 48 hours will be considered adequate to demonstrate clearance. If more than one culture set is drawn, all must show no growth at 48 hours to be considered evidence of clearance (e.g., 1 of 2 positive cultures would still be considered as ongoing bacteremia).
- Provider willing to treat with either dalbavancin for two doses, or standard of care intravenous monotherapy for at least 4 and no more than 8 weeks from randomization.
- Patients must be willing and able, if discharged, to return to the hospital or designated clinic for scheduled treatment, laboratory tests, or other procedures as required by the protocol.
- According to the site Principal Investigator or sub-investigator assessment, patients must be expected to survive with appropriate antibiotic therapy and appropriate supportive care throughout the study.
Who cannot join
- Uncomplicated bacteremia.*
- Uncomplicated Staphylococcus aureus bacteremia is defined as all of the following: exclusion of endocarditis by echocardiography; catheter-associated bacteremia and removal of catheter; no implanted prostheses; follow-up blood cultures drawn within 48 hours after initial set that do not grow screening pathogen and all follow-up blood cultures thereafter do not grow the screening pathogen; defervescence within 72 hours of initiating effective therapy; and no evidence of metastatic sites of infection.
- Infectious Central Nervous System events, including septic emboli, ischemic or hemorrhagic stroke, epidural abscess, or meningitis (prior/unrelated Central Nervous System events are not exclusion criteria).
- Known or suspected left-sided endocarditis or presence of a perivalvular abscess.
- Planned right-sided valve replacement surgery in the first 3 days following randomization.
- Presence of prosthetic heart valve, cardiac device** UNLESS removal is planned within 4 days post-randomization.
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- Implantable cardioverter defibrillator (ICD), permanent pacemaker, valve support ring, ventricular assist device (VAD).
- Presence of intravascular graft or intravascular material*** UNLESS removal is planned within 4 days post-randomization
- Excluding cardiac stents, inferior vena cava filters in place for >6 weeks, vascular stents in place for >6 weeks, non-hemodialysis grafts in place >90 days, and hemodialysis grafts not used within the past 12 months and not previously infected. A fistula constructed from native veins or a biologic vascular graft (without synthetic graft material) does not count as intravascular graft/material.
- Infected prosthetic joint or extravascular hardware UNLESS removal is planned within 4 days post-randomization OR hardware was placed >60 days before bacteremia and clinically appears uninfected.
- Polymicrobial bacteremia unless the non-Staphylococcus aureus organism is a contaminant.****
- Note: If a gram-negative bacteremia or fungemia develops after the qualifying S. aureus blood culture, AND the patient does not have right-sided endocarditis, AND the infection can be treated with an antibiotic without efficacy against the patient's S. aureus isolate (e.g. aztreonam), then the patient may remain eligible. Discussion with the DMID Medical Officer is strongly encouraged.
- Significant hepatic insufficiency (Child-Pugh class C or aspartate transaminase (AST)/alanine aminotransferase (ALT) values >5x Upper Limit Normal at the time of randomization).
- Immunosuppression*
- On chemotherapy or immunotherapy for active hematologic malignancy expected to cause > 7 days of absolute neutrophil count (ANC) < 100 cells/mm3, recent bone marrow transplant (in the past 90 days), solid organ transplantation within prior 3 months or receipt of augmented immunosuppression for rejection within 3 months, chronic granulomatous disease, human immunodeficiency virus (HIV) infection with a cluster of differentiation 4 (CD4) cell count < 50 cells/mm3 based on last known measurement or patient-reported value.
- History of hypersensitivity reaction to dalbavancin or other drugs of the glycopeptide class of antibiotics.
- Treatment with either dalbavancin or oritavancin in the 60 days prior to enrollment.
- Infection with Staphylococcus aureus not susceptible to dalbavancin (dalbavancin mean inhibitory concentration Minimum Inhibitory Concentration (MIC) > 0.25 µg/mL) or vancomycin (vancomycin Minimum Inhibitory Concentration (MIC) > 2 µg/mL).
- Planned treatment with concomitant systemic antibacterial therapy with potential efficacy against the patient's qualifying Staphylococcus aureus isolate, other than that allowed in the protocol.
- Pregnant/ nursing females.
- Females of childbearing potential must have a negative pregnancy test** within 48h of randomization and use effective contraception for trial duration.
- If the serum pregnancy test results cannot be obtained before randomization, a urine pregnancy test may be used for enrollment.
- Other medical or psychiatric condition that may, in the judgment of the investigator, increase the risk of study participation or interfere with interpretation of study results.
- Unwilling or unable to follow study procedures.
- Treatment with an investigational drug within 30 days preceding the first dose of study medication.
Trial locations and contacts
24 sites in 2 countries.
24 sites in 2 countries
United States23 sites
University of Alabama Hospital - Infectious Diseases
Birmingham, Alabama, 35233
Atrium Health ID Consultants & Infusion Care Specialists
Charlotte, North Carolina, 28209
Rush University Medical Center
Chicago, Illinois, 60612
Henry Ford Health System - Henry Ford Hospital
Detroit, Michigan, 48202-2608
Duke University Hospital - Infectious Diseases
Durham, North Carolina, 27710
University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine
Gainesville, Florida, 32610
East Carolina University - Infectious Diseases and Tropical/Travel Medicine Clinic
Greenville, North Carolina, 27834-9997
Prisma Health - Greenville Health System - Infectious Disease
Greenville, South Carolina, 29605
The University of Texas - MD Anderson Cancer Center - Infectious Diseases
Houston, Texas, 77030-4000
Ochsner Health - Ochsner Medical Center - Department of Infectious Diseases
New Orleans, Louisiana, 70121
New York Presbyterian Hospital - Weill Cornell Medical Center - Infectious Diseases
New York, New York, 10065-4870
University of Nebraska Medical Center - Infectious Diseases
Omaha, Nebraska, 68198-5400
University of Pittsburgh - Medicine - Infectious Diseases
Pittsburgh, Pennsylvania, 15213
Oregon Health and Science University - Adult Infectious Diseases Clinic
Portland, Oregon, 97239-3098
Carilion Roanoke Memorial Hospital
Roanoke, Virginia, 24014
Corewell Health - Infectious Disease
Royal Oak, Michigan, 48073-6757
University of California Davis Medical Center - Internal Medicine - Infectious Disease
Sacramento, California, 95817-1460
South Jersey Infectious Disease
Somers Point, New Jersey, 08244
SUNY Upstate Medical University - Infectious Disease Division
Syracuse, New York, 13210
University of South Florida Health - Internal Medicine
Tampa, Florida, 22612
Harbor UCLA Medical Center - Medicine - Infectious Diseases
Torrance, California, 90502-2006
Torrance Memorial Medical Center
Torrance, California, 90505
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
About this study
Official title: Dalbavancin as an Option for Treatment of S. Aureus Bacteremia (DOTS): A Phase 2b, Multicenter, Randomized, Open-Label, Assessor-Blinded Superiority Study to Compare the Efficacy and Safety of Dalbavancin to Standard of Care Antibiotic Therapy for the Completion of Treatment of Patients With Complicated S. Aureus Bacteremia
This is a Phase 2b clinical study, multicenter, randomized, open-label, assessor-blinded, superiority study. The study will compare dalbavancin to standard of care antibiotic therapy for the completion of therapy in patients with complicated bacteremia or right-sided native valve Infective Endocarditis (IE) caused by S. aureus who have cleared their baseline bacteremia. Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin or a standard of care antibiotic regimen that is based upon the identification and antibiotic susceptibility pattern of the baseline organism. Subjects randomized to the dalbavancin treatment group will receive 2 doses of dalbavancin intravenously (IV) 1 week apart (1500 mg on Day 1 and Day 8 after randomization, with renal dose adjustment if appropriate). Subjects randomized to the standard of care antibiotic therapy treatment group will receive an antibiotic regimen considered to be standard of care based on the methicillin susceptibility pattern of the pathogen isolated at baseline for a duration of 4 to 6 weeks and up to 8 weeks for patients with vertebral osteomyelitis/discitis. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at Day 70 of dalbavancin to that of standard of care antibiotic therapy used to consolidate therapy for the treatment of subjects with complicated S. aureus bacteremia in the intent-to-treat population (ITT).
Read the detailed description
This is a Phase 2b clinical study, multicenter, randomized, open-label, assessor-blinded, superiority study. The study will compare dalbavancin to standard of care antibiotic therapy for the completion of therapy in patients with complicated bacteremia or right-sided native valve Infective Endocarditis (IE) caused by S. aureus who have cleared their baseline bacteremia. Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin or a standard of care antibiotic regimen that is based upon the identification and antibiotic susceptibility pattern of the baseline organism. Subjects randomized to the dalbavancin treatment group will receive 2 doses of dalbavancin intravenously (IV) 1 week apart (1500 mg on Day 1 and Day 8 after randomization, with renal dose adjustment if appropriate). Subjects randomized to the standard of care antibiotic therapy treatment group will receive an antibiotic regimen considered to be standard of care based on the methicillin susceptibility pattern of the pathogen isolated at baseline for a duration of 4 to 6 weeks and up to 8 weeks for patients with vertebral osteomyelitis/discitis. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at Day 70 of dalbavancin to that of standard of care antibiotic therapy used to consolidate therapy for the treatment of subjects with complicated S. aureus bacteremia in the intent-to-treat population (ITT). The secondary objectives are 1) to compare the clinical outcomes of dalbavancin with the standard of care antibiotic therapy at day 70 in the modified intent-to-treat population (mITT). 2) to compare the safety of dalbavancin with that of the standard of care treatment in the modified intent-to-treat population (mITT). 3) to compare each individual component of the Desirability of Outcome Ranking (DOOR) outcome by treatment arm, in the intent-to-treat population.
- Conditions
- Staphylococcal Bacteraemia
- Being tested
- Cefazolin, Dalbavancin, Daptomycin, Nafcillin, Oxacillin
- Keywords
- Bacteremia, Dalbavancin, DOTS, Efficacy, Safety, Staphylococcus aureus
- Medical subject headings
- Bacteremia, Staphylococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CefazolinDrug
Cefazolin is a semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. Cefazolin (2 g will be administrated intravenously (IV) every 8 hours for 4-6 weeks)
DalbavancinDrug
A second-generation lipoglycopeptide antibiotic synthesized from a fermentation product of Nonomuraea species
DaptomycinDrug
Daptomycin (USA) or Cubicin (Spain) is a cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Daptomycin (6-10 mg/kg will be administrated intravenously (IV) daily for 4-6 weeks
NafcillinDrug
Nafcillin is a semi-synthetic antibiotic related to penicillin. Nafcillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks)
OxacillinDrug
Oxacillin is an antibiotic used in resistant staphylococci infections. Oxacillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks
VancomycinDrug
Vancomycin is a glycopeptide antibiotic product of the organism Amycolatopsis orientalis. Vancomycin (dose per local standard of care × 4-6 weeks)
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (Dalbavancin) | Experimental | Dalbavancin 1500 mg will be administrated intravenously (IV) over 30 (-/+10) minutes on Day 1 and 1500 mg IV over 30 (-/+10) minutes on Day 8, renally dose-adjusted to 1125 mg for subjects with Creatinine Clearance (CrCl) <30 and not on dialysis. N=100 Receives: Drug: Dalbavancin |
| Arm 2 (Standard of Care) | Active comparator | For Methicillin-sensitive Staphylococcus aureus (MSSA): nafcillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks) OR oxacillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks OR cefazolin (2 g will be administrated intravenously (IV) every 8 hours for 4-6 weeks) For Methicillin-resistant Staphylococcus aureus (MRSA): vancomycin (dose per local standard of care × 4-6 weeks) OR daptomycin (6-10 mg/kg will be administrated intravenously (IV) daily for 4-6 weeks). N=100 Receives: Drug: Cefazolin; Drug: Daptomycin; Drug: Nafcillin; Drug: Oxacillin; Drug: Vancomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Desirability of Outcome Ranking (DOOR)
DOOR is a composite endpoint assessed by: (1) Clinical Failure: Lack of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated for its treatment; (2) Infectious Complications such as: Endocarditis, New evidence of metastatic foci of infection, relapse - isolation of baseline S. aureus pathogen from a blood culture drawn after randomization, readmission for subsequent care of indication under study, need for additional unplanned source control procedures, or change in antibiotic therapy due to inadequate clinical response; (3) Serious Adverse Events (SAEs); (4) Adverse Events (AEs) Leading to Study Drug Discontinuation; and (5) Death. Clinical failure and infectious complications were assessed by a blinded adjudication committee. Participants missing clinical failure were treated as having clinical failure for calculation of DOOR.
Measured: Day 70
Secondary outcomes (8)
Frequency of Clinical Efficacy
Number of participants that had clinical efficacy at Day 70. Clinical efficacy is defined as none of: (1) Clinical Failure: Lack of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated for its treatment; (2) Infectious Complications such as: Endocarditis, New evidence of metastatic foci of infection, relapse - isolation of baseline S. aureus pathogen from a blood culture drawn after randomization, readmission for subsequent care of indication under study, need for additional unplanned source control procedures, or change in antibiotic therapy due to inadequate clinical response; and (3) Death. Clinical failure and infectious complications are assessed by a blinded adjudication committee. Participants missing clinical failure are treated as not having clinical efficacy.
Measured: Day 70
Frequency of SAEs
Number of participants that experience any SAEs from Day 1 to study completion (Day 70 or Day 180 for participants in the osteomyelitis subset). An AE is considered serious if, in the view of either the site principal investigator or sponsor, it results in: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Measured: Day 1 through Day 180
Frequency of AEs Leading to Study Drug Discontinuation
Number of participants that experience any AEs leading to study drug discontinuation from Day 1 to study completion (Day 70 or Day 180 for participants in the osteomyelitis subset).
Measured: Day 1 through Day 180
Frequency of Clinical Failure (A Component of DOOR)
Number of participants who had clinical failure at Day 70, used for DOOR at Day 70. Clinical Failure is defined as lack of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated for its treatment. Clinical failure is assessed by a blinded adjudication committee. Participants missing clinical failure are treated as having clinical failure.
Measured: Day 70
Frequency of Infectious Complications (A Component of DOOR)
Number of participants that experience any infectious complications from Day 1 through Day 70, used for DOOR at Day 70. Infectious complications include endocarditis, new evidence of metastatic foci of infection, relapse - isolation of baseline S. aureus pathogen from a blood culture drawn after randomization, readmission for subsequent care of indication under study, need for additional unplanned source control procedures, or change in antibiotic therapy due to inadequate clinical response. Infectious complications are assessed by a blinded adjudication committee.
Measured: Day 1 through Day 70
Frequency of SAEs (A Component of DOOR)
Number of participants that experience any SAEs from Day 1 to Day 70, used for DOOR at Day 70. An AE is considered serious if, in the view of either the site principal investigator or sponsor, it results in: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Measured: Day 1 through Day 70
Frequency of AEs Leading to Study Drug Discontinuation (A Component of DOOR)
Number of participants that experience any AEs leading to study drug discontinuation from Day 1 to Day 70, used for DOOR at Day 70.
Measured: Day 1 through Day 70
Frequency of All-Cause Mortality (A Component of DOOR)
Number of participants who passed away from Day 1 to Day 70, used for DOOR at Day 70.
Measured: Day 1 through Day 70
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2021
- Study start22 Apr 2021
- Primary completion6 Oct 2023
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Staphylococcal BacteraemiaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04775953
- Sponsor's protocol ID
- 20-0002
- Other IDs
- 5UM1AI104681-12
- Status last verified
- 10 Feb 2022
- First submitted
- 25 Feb 2021
- Last updated
- 10 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Lodise TP, Turner NA, Hamasaki T, Fishbane N, Ghazaryan V, Wall A, Ge L, Wu Q, Zeng L, Riccobene T, Patel R, Zaharoff S, Rappo U, Evans S, Fowler VG Jr, Chambers HF, Holland TL; Antibacterial Resistance Leadership Group. Pharmacokinetics of Dalbavancin in Complicated Staphylococcus aureus Bacteremia: A Secondary Analysis of the DOTS Randomized Clinical Trial. JAMA Netw Open. 2026 Apr 1;9(4):e2611652. doi: 10.1001/jamanetworkopen.2026.11652.
PubMed 41999282Turner NA, Hamasaki T, Doernberg SB, Lodise TP, King HA, Ghazaryan V, Cosgrove SE, Jenkins TC, Liu C, Sharma S, Zaharoff S, Wahid L, Renard VJ, Cook P, Raad I, Hachem R, Chaftari AM, Sims M, DeMarco C, Miller LG, McCarthy MW, Morse CG, Lucasti C, Forrest GN, Cherabuddi K, Polk C, Fazili T, Rupp ME, Thompson GR 3rd, Kim K, Strnad L, Schnee AE, McKinnell JA, Ramesh M, Silveira FP, McCarty TP, Lee TC, McDonald EG, Paolino K, Wiegand K, Wall A, Riccobene T, Patel R, Rappo U, Evans S, Chambers HF, Fowler VG Jr, Holland TL; Antibacterial Resistance Leadership Group. Dalbavancin for Treatment of Staphylococcus aureus Bacteremia: The DOTS Randomized Clinical Trial. JAMA. 2025 Aug 13;334(10):866-77. doi: 10.1001/jama.2025.12543. Online ahead of print.
PubMed 40802264Turner 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.
PubMed 35578360
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dalbavancin as an Option for Treatment of S. Aureus Bacteremia (DOTS): A Phase 2b, Multicenter, Randomized, Open-Label, Assessor-Blinded Superiority Study to Compare the Efficacy and Safety of Dalbavancin to Standard of Care Antibiotic Therapy for the Completion of Treatment of Patients With Complicated S. Aureus Bacteremia
- ClinicalTrials.gov ID
- NCT04775953
- Acronym / sponsor ID
- 20-0002
- Conditions
- Staphylococcal Bacteraemia
- Keywords
- Bacteremia, Dalbavancin, DOTS, Efficacy, Safety, Staphylococcus aureus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 22 Apr 2021 (actual)
- Primary completion
- 6 Oct 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 1 Mar 2021 (actual)
- Results
- Posted 22 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2b clinical study, multicenter, randomized, open-label, assessor-blinded, superiority study. The study will compare dalbavancin to standard of care antibiotic therapy for the completion of therapy in patients with complicated bacteremia or right-sided native valve Infective Endocarditis (IE) caused by S. aureus who have cleared their baseline bacteremia. Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin or a standard of care antibiotic regimen that is based upon the identification and antibiotic susceptibility pattern of the baseline organism. Subjects randomized to the dalbavancin treatment group will receive 2 doses of dalbavancin intravenously (IV) 1 week apart (1500 mg on Day 1 and Day 8 after randomization, with renal dose adjustment if appropriate). Subjects randomized to the standard of care antibiotic therapy treatment group will receive an antibiotic regimen considered to be standard of care based on the methicillin susceptibility pattern of the pathogen isolated at baseline for a duration of 4 to 6 weeks and up to 8 weeks for patients with vertebral osteomyelitis/discitis. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at Day 70 of dalbavancin to that of standard of care antibiotic therapy used to consolidate therapy for the treatment of subjects with complicated S. aureus bacteremia in the intent-to-treat population (ITT).
Detailed description
This is a Phase 2b clinical study, multicenter, randomized, open-label, assessor-blinded, superiority study. The study will compare dalbavancin to standard of care antibiotic therapy for the completion of therapy in patients with complicated bacteremia or right-sided native valve Infective Endocarditis (IE) caused by S. aureus who have cleared their baseline bacteremia. Approximately 200 subjects will be randomized 1:1 to receive either dalbavancin or a standard of care antibiotic regimen that is based upon the identification and antibiotic susceptibility pattern of the baseline organism. Subjects randomized to the dalbavancin treatment group will receive 2 doses of dalbavancin intravenously (IV) 1 week apart (1500 mg on Day 1 and Day 8 after randomization, with renal dose adjustment if appropriate). Subjects randomized to the standard of care antibiotic therapy treatment group will receive an antibiotic regimen considered to be standard of care based on the methicillin susceptibility pattern of the pathogen isolated at baseline for a duration of 4 to 6 weeks and up to 8 weeks for patients with vertebral osteomyelitis/discitis. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at Day 70 of dalbavancin to that of standard of care antibiotic therapy used to consolidate therapy for the treatment of subjects with complicated S. aureus bacteremia in the intent-to-treat population (ITT). The secondary objectives are 1) to compare the clinical outcomes of dalbavancin with the standard of care antibiotic therapy at day 70 in the modified intent-to-treat population (mITT). 2) to compare the safety of dalbavancin with that of the standard of care treatment in the modified intent-to-treat population (mITT). 3) to compare each individual component of the Desirability of Outcome Ranking (DOOR) outcome by treatment arm, in the intent-to-treat population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (Dalbavancin) | Experimental | Drug: DalbavancinDalbavancin 1500 mg will be administrated intravenously (IV) over 30 (-/+10) minutes on Day 1 and 1500 mg IV over 30 (-/+10) minutes on Day 8, renally dose-adjusted to 1125 mg for subjects with Creatinine Clearance (CrCl) <30 and not on dialysis. N=100 |
| Arm 2 (Standard of Care) | Active comparator | Drug: Cefazolin, Drug: Daptomycin, Drug: Nafcillin, Drug: Oxacillin, Drug: VancomycinFor Methicillin-sensitive Staphylococcus aureus (MSSA): nafcillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks) OR oxacillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks OR cefazolin (2 g will be administrated intravenously (IV) every 8 hours for 4-6 weeks) For Methicillin-resistant Staphylococcus aureus (MRSA): vancomycin (dose per local standard of care × 4-6 weeks) OR daptomycin (6-10 mg/kg will be administrated intravenously (IV) daily for 4-6 weeks). N=100 |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Written informed consent obtained from the patient or legally authorized representative before the initiation of any study-specific procedures.
- Patients > / = to 18 years old.
- A diagnosis of complicated Staphylococcus aureus (either Methicillin-sensitive Staphylococcus aureus or Methicillin-resistant Staphylococcus aureus) bloodstream infection.
- Treated with effective antibiotic therapy for at least 72 hours (maximum 10 days).*
- Ten consecutive days prior to randomization is the maximum allowed treatment duration. If a subject has received intermittent or incomplete therapy earlier in the treatment course for this episode of S. aureus bacteremia, then discuss with the protocol PI and DMID Medical Officer prior to enrollment.
Key exclusion criteria (25 listed)
- Uncomplicated bacteremia.*
- Uncomplicated Staphylococcus aureus bacteremia is defined as all of the following: exclusion of endocarditis by echocardiography; catheter-associated bacteremia and removal of catheter; no implanted prostheses; follow-up blood cultures drawn within 48 hours after initial set that do not grow screening pathogen and all follow-up blood cultures thereafter do not grow the screening pathogen; defervescence within 72 hours of initiating effective therapy; and no evidence of metastatic sites of infection.
- Infectious Central Nervous System events, including septic emboli, ischemic or hemorrhagic stroke, epidural abscess, or meningitis (prior/unrelated Central Nervous System events are not exclusion criteria).
- Known or suspected left-sided endocarditis or presence of a perivalvular abscess.
- Planned right-sided valve replacement surgery in the first 3 days following randomization.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CefazolinCefazolin is a semisynthetic cephalosporin analog with broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. Cefazolin (2 g will be administrated intravenously (IV) every 8 hours for 4-6 weeks) | Drug | Arm 2 (Standard of Care) |
| DalbavancinA second-generation lipoglycopeptide antibiotic synthesized from a fermentation product of Nonomuraea species | Drug | Arm 1 (Dalbavancin) |
| DaptomycinDaptomycin (USA) or Cubicin (Spain) is a cyclic lipopeptide antibiotic that inhibits gram-positive bacteria. Daptomycin (6-10 mg/kg will be administrated intravenously (IV) daily for 4-6 weeks | Drug | Arm 2 (Standard of Care) |
| NafcillinNafcillin is a semi-synthetic antibiotic related to penicillin. Nafcillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks) | Drug | Arm 2 (Standard of Care) |
| OxacillinOxacillin is an antibiotic used in resistant staphylococci infections. Oxacillin (2 g will be administrated intravenously (IV) every 4 hours for 4-6 weeks | Drug | Arm 2 (Standard of Care) |
| VancomycinVancomycin is a glycopeptide antibiotic product of the organism Amycolatopsis orientalis. Vancomycin (dose per local standard of care × 4-6 weeks) | Drug | Arm 2 (Standard of Care) |
Primary outcome
Desirability of Outcome Ranking (DOOR)
Time frame: Day 70
DOOR is a composite endpoint assessed by: (1) Clinical Failure: Lack of resolution of clinical signs and symptoms of S. aureus bacteremia such that no additional antibiotic therapy is required or anticipated for its treatment; (2) Infectious Complications such as: Endocarditis, New evidence of metastatic foci of infection, relapse - isolation of baseline S. aureus pathogen from a blood culture drawn after randomization, readmission for subsequent care of indication under study, need for additional unplanned source control procedures, or change in antibiotic therapy due to inadequate clinical response; (3) Serious Adverse Events (SAEs); (4) Adverse Events (AEs) Leading to Study Drug Discontinuation; and (5) Death. Clinical failure and infectious complications were assessed by a blinded adjudication committee. Participants missing clinical failure were treated as having clinical failure for calculation of DOOR.
8 secondary outcomes
Frequency of Clinical Efficacy
Time frame: Day 70
Frequency of SAEs
Time frame: Day 1 through Day 180
Frequency of AEs Leading to Study Drug Discontinuation
Time frame: Day 1 through Day 180
Frequency of Clinical Failure (A Component of DOOR)
Time frame: Day 70
Frequency of Infectious Complications (A Component of DOOR)
Time frame: Day 1 through Day 70
Frequency of SAEs (A Component of DOOR)
Time frame: Day 1 through Day 70
Frequency of AEs Leading to Study Drug Discontinuation (A Component of DOOR)
Time frame: Day 1 through Day 70
Frequency of All-Cause Mortality (A Component of DOOR)
Time frame: Day 1 through Day 70
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41999282Lodise TP, Turner NA, Hamasaki T, Fishbane N, Ghazaryan V, Wall A, Ge L, Wu Q, Zeng L, Riccobene T, Patel R, Zaharoff S, Rappo U, Evans S, Fowler VG Jr, Chambers HF, Holland TL; Antibacterial Resistance Leadership Group. Pharmacokinetics of Dalbavancin in Complicated Staphylococcus aureus Bacteremia: A Secondary Analysis of the DOTS Randomized Clinical Trial. JAMA Netw Open. 2026 Apr 1;9(4):e2611652. doi: 10.1001/jamanetworkopen.2026.11652.
- Derived from this study: PubMed 40802264Turner NA, Hamasaki T, Doernberg SB, Lodise TP, King HA, Ghazaryan V, Cosgrove SE, Jenkins TC, Liu C, Sharma S, Zaharoff S, Wahid L, Renard VJ, Cook P, Raad I, Hachem R, Chaftari AM, Sims M, DeMarco C, Miller LG, McCarthy MW, Morse CG, Lucasti C, Forrest GN, Cherabuddi K, Polk C, Fazili T, Rupp ME, Thompson GR 3rd, Kim K, Strnad L, Schnee AE, McKinnell JA, Ramesh M, Silveira FP, McCarty TP, Lee TC, McDonald EG, Paolino K, Wiegand K, Wall A, Riccobene T, Patel R, Rappo U, Evans S, Chambers HF, Fowler VG Jr, Holland TL; Antibacterial Resistance Leadership Group. Dalbavancin for Treatment of Staphylococcus aureus Bacteremia: The DOTS Randomized Clinical Trial. JAMA. 2025 Aug 13;334(10):866-77. doi: 10.1001/jama.2025.12543. Online ahead of print.
- Derived from this study: PubMed 35578360Turner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cefazolin, Dalbavancin and Daptomycin in people with Staphylococcal Bacteraemia, run by National Institute of Allergy and Infectious Diseases (NIAID) at 24 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Desirability of Outcome Ranking (DOOR) (time frame: Day 70). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04775953, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2024.