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

Study Overview
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Brief Summary
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This is a multicenter, randomized, open-label, noninferiority trial of telavancin versus standard IV therapy control (e.g., vancomycin, daptomycin, anti-staphylococcal penicillin (PCN), or cefazolin) in the treatment of subjects with complicated Staphylococcus aureus (S. aureus) bacteremia and SA right-sided infective endocarditis (SA-RIE).

Official Title
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A Phase 3 Multicenter, Randomized, Open-label, Clinical Trial of Telavancin Versus Standard Intravenous Therapy in the Treatment of Subjects With Staphylococcus Aureus Bacteremia Including Infective Endocarditis

Conditions
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Bacteremia

Intervention / Treatment
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* Drug: Telavancin
* Drug: Vancomycin
* Drug: Daptomycin
* Drug: Synthetic penicillin
* Drug: Cefazolin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telavancin<br>7.5 mg/kg administered intravenously once every 24 hours daily over 60 minutes | Drug: Telavancin<br> <br> |
| Active Comparator: Standard of care<br>Vancomycin, Daptomycin, synthetic penicillin or Cefazolin | Drug: Vancomycin<br> <br> Drug: Daptomycin<br> <br> * Other names: Cubicin;Drug: Synthetic penicillin<br> <br> * Other names: Cloxacillin;Drug: Cefazolin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) | 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). Alive at TOC Resolution of all clinical signed and symptoms of the Staphylococcus aureus (S. aureus) infection at TOC No evidence of microbiological persistence of relapse No new foci of metastatic S. aureus infection after Day 8 | Up to 8 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacteremia, Staphylococcus aureus