Staphylococcus aureus Bacteremia Including Infective Endocarditis
Conditions
Interventions
Experimental group: In total, 124 subjects will receive Telavancin, 7.5 mg/kg, intravenously (IV) in 100 to 250 mL over 60 (+/- 10) minutes, once every 24 hours for 2 to 6 weeks. For Brazil, 6 subject
Daptomycin (recommended dose of 6 mg/kg IV q24 hours)
Anti-staphylococcal penicillin (ie, nafcillin, oxacillin, or cloxacillin) recommended dose of 2 gm IV q4 hours or 12 gm IV continuous infusion over 24 hours
or Cefazolin (recommended dose of 2 gm IV q8 hours). For Brazil, 5 subjects are expected.
Drug
Sponsors
Instituto Dante Pazzanese de Cardiologia
INC Research BR Serviços de Pesquisas Clínicas Ltda.
Eligibility
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Male or female at least 18 years old at the time of consent; subject has signed an ICF; at least one blood culture positive for S. aureus within 48 hours before randomization; in addition to the QBC, subject must have at least one of the following signs or symptoms of bacteremia: temperature higher or equal to 38.0°C, white blood cell (WBC) count higher 10,000 or less than 4,000 cells/µL, or higher 10% immature neutrophils (bands) regardless of total peripheral WBC count; tachycardia (heart rate higher 90 bpm); tachypnea (respiratory rate higher 20 breaths/min); hypotension (systolic blood pressure less than 90 mmHg); signs and symptoms of localized catheter-related infection; subject must, at enrollment, 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) known bacteremia with at least one of the following risk factors for complicated bacteremia: any venous catheter considered to be the source of the infection, demonstrated by inflammation or purulent drainage from the catheter insertion site AND evidence of catheter-associated thrombosis upon removal; a central venous catheter considered to be the source of infection; a long-term intravascular catheter considered to be the source of infection; new onset cardiac murmur consistent with tricuspid regurgitation; community onset bacteremia; pathogen known to be MRSA at enrollment; duration of symptoms higher or equal to 2 days at time of presentation (prior to start of antibiotic therapy); skin exam findings suggesting acute systemic infection; willing to receive intravenous antibiotics for the duration of treatment; expected survival of at least 3 months; female subjects must be non-pregnant and non-lactating; if sexually active, must agree to use a highly effective method of birth control with partners of childbearing potential during the study and for 1 month after study drug dosing; considered likely to comply with the study procedures and to return for scheduled evaluations.
Exclusion criteria
Exclusion criteria: Treatment with any potentially effective (anti-staphylococcal) systemic antibiotic for more than 60 hours within 7 days before randomization; requirement or anticipated requirement of non-study systemic antibiotics during the study; 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; known or suspected left-sided infective endocarditis (LIE), at enrollment, according to Modified Duke Criteria; at the time of enrollment, known or highly suspected osteomyelitis, meningitis, or metastatic septic foci involving the central nervous system (CNS); Known at the time of enrollment to have MRSA bacteremia that is non susceptible to daptomycin AND has a vancomycin MIC higher or equal to 2 microg/mL; confirmed evidence 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; previous participation in an anti-infective study during the past 12 months; history of significant hypersensitivity, allergy or intolerance to telavancin; solid organ transplantation or bone marrow transplantation within 6 months before randomization; severe neutropenia, defined as an absolute neutrophil count (ANC) less than 500 cells per microliter, or expected development of severe neutropenia during study; known or suspected human immunodeficiency (HIV) infection with a CD4+ T-cell count less than 200/µl within the previous 6 months; subjects requiring concomitant administration of anti-coagulation therapy AND requiring specific coagulation testing known to have interference by telavancin; severe liver disease, ie, Child-Pugh Class C, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 10 times the upper limit of normal (ULN); requirement for acute renal replacement therapy; or acute kidney injury (AKI) defined as an acute decrease in creatinine clearance (CrCl) to less than 30 mL/min and at least one of the following: higher or equal to 2x increase in serum Cr or 50% decrease in glomerular filtration rate (GFR) within the 2 weeks prior to enrollment (RIFLE stage 2 injury); oliguria defined as urine output less than 0.5 mL/kg per hour for higher ot equal to 12 hours at any time during screening; Shock or hypotension (supine systolic blood pressure less than 80 mm Hg) unresponsive to fluids or pressors within 24 hours prior to randomization; QTc higher than 460 ms (using either the Bazett or Fridericia formula), congenital long QT syndrome, uncompensated or new onset heart failure, aortic stenosis, aortic insufficiency, or mitral insufficiency; serum creatine kinase (CK) higher or equal to 2000 U/L; breast-feeding or pregnant or intending to become pregnant (self or partner) at any time during the study; any other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject or would render the subject unable to comply with the protocol; or any other condition that in the opinion of the investigator may confound the data.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinical success or failure at Test of Cure (TOC) visit determined by the investigator and adjudicated by the blinded IEAC. The point estimate and confidence interval (CI) for the treatment difference will be calculated using the Mantel-Haenszel approach. | — |
Secondary
| Measure | Time frame |
|---|---|
| Not applicable. | — |
Countries
Argentina, Brazil, Colombia, Czech Republic, Georgia, Germany, Hungary, Italy, Latvia, Mexico, Poland, Portugal, Romania, Spain, United States
Contacts
Public ContactAnna Coimbra
INC Research BR Serviços de Pesquisas Clínicas Ltda.
Outcome results
None listed