A Phase 3 Telavancin Staphylococcus Aureus (S. Aureus) Bacteremia Trial

• Telavancin (Drug)
• Vancomycin (Drug)
• Daptomycin (Drug), also known as Cubicin
• Synthetic penicillin (Drug), also known as Nafcillin, Oxacillin, Cloxacillin
• Cefazolin (Drug)

Primary outcomes

• Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) [Up to 8 weeks]: The efficacy endpoint of clinical outcome of cure at the test of cure (TOC) was determined by subjects who meet all of the following criteria, as determined by the investigator and adjudicated by the blinded independent efficacy adjudication committee (IEAC). 1. Alive at TOC 2. Resolution of all clinical signed and symptoms of the Staphylococcus aureus (S. aureus) infection at TOC 3. No evidence of microbiological persistence of relapse 4. No new foci of metastatic S. aureus infection after Day 8

Secondary outcomes

• Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population [Up to 8 weeks]: The efficacy endpoint of Investigator clinical outcome of cure at the test of cure (TOC) was determined by the following criteria: 1. Subject alive at TOC 2. Resolution of all clinical signs and symptoms of the S. aureus infection at TOC (unless explained by a more likely alternative diagnosis) 3. No evidence of microbiological persistence or relapse 4. No new foci of metastatic S. aureus infection after Day 8
• Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population [Up to 8 weeks]: This efficacy endpoint was determined to be a clinical failure if the subject switched study antibiotic due to lack of clinical response
• Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations [Day 8]: After Day 8, any sign or symptom leading to a subsequent confirmed diagnosis of a new metastatic foci of S. aureus infection

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* 18 years of age or older with at least one blood culture positive for S. aureus within 48 hours before randomization
* At least one of the following signs or symptoms of bacteremia:

  * Temperature ≥ 38.0°C
  * White blood cell (WBC) count > 10,000 or < 4,000 cells/µL or > 10% immature neutrophils (bands)
  * Tachycardia (heart rate > 90 bpm)
  * Tachypnea (respiratory rate > 20 breaths/min)
  * Hypotension (systolic blood pressure < 90 mmHg)
  * Signs or symptoms of localized catheter-related infection
* At enrollment, subjects must have either 1) known right-sided infective endocarditis by Modified Duke's criteria 2) known complicated bacteremia, demonstrated as signs or symptoms of metastatic foci of S. aureus infection or 3) at least one risk factor for complicated bacteremia.

Exclusion Criteria:

* Treatment with any potentially effective (anti-staphylococcal) systemic antibiotic for more than 60 hours within 7 days before randomization. EXCEPTION: Documented resistance to the prior systemic antibacterial therapy
* Presence of an infection source that will not be managed or controlled within the first 3 days of study drug treatment
* Presence of prosthetic cardiac valve or cardiac device (eg, implantable cardioverter defibrillator \[ICD\]), permanent pacemaker, or cardiac valve support ring)
* Known or suspected left-sided infective endocarditis (LIE), by Modified Duke Criteria. NOTE: Right-sided infective endocarditis (RIE) is permitted
* Known or suspected osteomyelitis or meningitis. NOTE: Evidence of metastatic complications related to the primary infection such as right-sided endocarditis, septic arthritis, septic pulmonary emboli are permitted. S. aureus pneumonia is permitted
* Confirmed evidence (identification or gram stain) of a mixed polymicrobial infection with a Gram-negative pathogen that requires non-study antibiotic treatment with agent(s) that have activity against Gram-negative pathogens

Participant flow

Outcome results

• Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) (Primary), Count of participants, Participants: Telavancin 22; Standard of Care 27
• Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population (Secondary), Count of participants, Participants: Telavancin 26; Standard of Care 31
• Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population (Secondary), Count of participants, Participants: Telavancin 28; Standard of Care 36
• Number of Participants With the Development of a New Metastatic Foci of S. Aureus Infection at Test of Cure (TOC) in the Microbiological All-treated (mAT) Populations (Secondary), Count of participants, Participants: Telavancin 6; Standard of Care 3

Adverse events

Time frame: 38 months

Serious adverse events by term

Other adverse events by term

Limitations and caveats: At the interim analysis, study was deemed to be inadequately powered \& terminated prematurely.

• Study Protocol (PDF, 2018-01-16)
• Statistical Analysis Plan (PDF, 2018-04-26)

• Medical Monitor, Study director, Cumberland Pharmaceuticals