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

  • STATUS
    Recruiting
  • End date
    Nov 9, 2023
  • participants needed
    200
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Send
Updated on 25 October 2022
See if I qualify

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 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).

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.

Details
Condition Staphylococcal Bacteraemia
Treatment Vancomycin, Daptomycin, Cefazolin, Dalbavancin, Nafcillin, Nafcillin, Oxacillin, Oxacillin
Clinical Study IdentifierNCT04775953
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on25 October 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

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)
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
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
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
Two negative blood cultures incubated for 48 hours are preferred. However
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
if only a single blood culture set is drawn, no growth at 48 hours will be
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
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)

Exclusion Criteria

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
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
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
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
Implantable cardioverter defibrillator (ICD), permanent pacemaker, valve
Significant hepatic insufficiency (Child-Pugh class C or aspartate transaminase (AST)/alanine aminotransferase (ALT) values >5x Upper Limit Normal at the time of randomization)
days, and hemodialysis grafts not used within the past 12 months and not
support ring, ventricular assist device (VAD)
Immunosuppression
previously infected. A fistula constructed from native veins (without
synthetic graft material) does not count as intravascular graft/material
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
History of hypersensitivity reaction to dalbavancin or other drugs of the glycopeptide class of antibiotics
patient may remain eligible. Discussion with the DMID Medical Officer is
Treatment with either dalbavancin or oritavancin in the 60 days prior to enrollment
strongly encouraged
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)
expected to cause > 7 days of absolute neutrophil count (ANC) < 100 cells/mm3
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
recent bone marrow transplant (in the past 90 days), solid organ
Pregnant/ nursing females
transplantation within prior 3 months or receipt of augmented
Females of childbearing potential must have a negative pregnancy test within 48h of randomization and use effective contraception for trial duration
immunosuppression for rejection within 3 months, chronic granulomatous
On chemotherapy or immunotherapy for active hematologic malignancy
differentiation 4 (CD4) cell count < 50 cells/mm3 based on last known
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
disease, human immunodeficiency virus (HIV) infection with a cluster of
measurement or patient-reported value
If the serum pregnancy test results cannot be obtained before
randomization, a urine pregnancy test may be used for enrollment
Clear my responses
Read more

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name
Edit Delete

Added by • 

 • 

Private

Edit Delete

Reply by • • Private
Edit Delete

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note