Clinical Trial to evaluate the safety and tolerability of telavancin compared with standard intravenous therapy in the treatment of S. aureus bacteremia

Phase 1

• Conditions: MedDRA version: 20.0Level: LLTClassification code 10004035Term: Bacterial infection due to staphylococcus aureusSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]; Staphylococcus aureus Bacteremia Including Infective Endocarditis

• Registration Number: EUCTR2014-004372-27-DE
• Lead Sponsor: Theravance Biopharma Ireland Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-12-08
• Last Update Posted: 25 June 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 248

Inclusion Criteria

1.Male or female at least 18 years old at the time of consent
2.Subject has signed an informed consent form. If a subject is unable to give consent, when legally permitted, consent must be obtained from the subject’s legally acceptable representative.
NOTE: Subject, or appropriate legal representative, must be able to communicate effectively with investigator and site staff
3.At least one blood culture positive for S. aureus within 48 hours before randomisation, referred to as the QBC
4.In addition to the QBC, subject must have 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) regardless of total peripheral WBC count
•Tachycardia (heart rate > 90 bpm)
•Tachypnea (respiratory rate >20 breaths/min)
•Hypotension (systolic blood pressure <90 mmHg)
•Signs and symptoms of localized catheter-related infection (tenderness and/or pain, erythema, swelling, purulent exudate within 2 cm of entry site)
5.Subject must, at enrollment, have either 1) known right-sided infective endocarditis by Modified Duke’s Criteria, 2) known CB, demonstrated as signs or symptoms of metastatic foci of S. aureus infection (eg, any infection remote from the primary focus caused by hematogenous seeding or extension of infection beyond the primary focus), or 3) known bacteraemia with at least one of the following risk factors for CB[25-28].
•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. NOTE: A peripheral venous catheter with just inflammation or purulent drainage from the catheter insertion site without evidence of thrombus is not consistent with CB.
• A central venous catheter (CVC) considered to be the source of infection, demonstrated by inflammation or purulent drainage from the CVC insertion site or presence of thrombus on ultrasound
•A long-term intravascular catheter (eg, tunneled cuffed intravascular catheter or subcutaneous port catheter), considered to be the source of infection, demonstrated by inflammation or purulent drainage from the catheter insertion site or presence of thrombus on ultrasound
•New onset cardiac murmur consistent with tricuspid regurgitation
•Community onset bacteremia (eg, subject does not live in a healthcare facility)
•Pathogen known to be MRSA at enrollment
•Duration of symptoms =2 days at time of presentation (prior to start of antibiotic therapy)
•Skin exam findings suggesting acute systemic infection (ie, petechiae, vasculitis, infarcts, ecchymoses or pustules due to the infection)
6.Willing to receive intravenous antibiotics for the duration of treatment
7.Expected survival of at least 3 months
8.Female subjects must be non-pregnant and non-lactating. If a female subject is of childbearing potential, must have a documented negative pregnancy test at screening

NOTE: All females are considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 2 years) or documented to be surgically sterile (bilateral tubal ligation or total hysterectomy). A subject may be admitted to the study on the basis of a negative urine pregnancy test (local laboratory), pending the result of the serum pregnancy test.
9.If sexually active, must agree to use a highly effectiv

Exclusion Criteria

1.Treatment with any potentially effective (anti-staphylococcal) systemic antibiotic for more than 60 hours within 7 days before randomization (preferable to have no more than 48 hours)
EXCEPTION: Documented resistance to the prior systemic antibacterial therapy, confirmed by a microbiological laboratory report
2.Requirement or anticipated requirement of non-study systemic antibiotics during the study
3.Presence of an infection source (eg, intravascular line, abscess, septic arthritis, infected prosthetic material, wound) that will not be managed or controlled (eg, removal or replacement of the infected line, drainage of abscess, aspiration or drainage of septic arthritis, removal or replacement of infected prosthesis, or debridement of infected wound) within the first 3 days of study drug treatment
4.Presence of prosthetic cardiac valve or cardiac device (eg, implantable cardioverter defibrillator [ICD]), permanent pacemaker, or cardiac valve support ring)
5.Known or suspected LIE at enrolment, according to Modified Duke Criteria (App. 1). Right-sided infective endocarditis (RIE) is permitted. If the subject is diagnosed with LIE after enrollment, subject will be allowed to remain on study.
6.At the time of enrolment known or highly suspected osteomyelitis, meningitis or metastatic septic foci involving the CNS. Investigators should use clinical judgment to determine whether additional imaging studies (eg, X-ray, computed tomography scan, magnetic resonance imaging) are indicated at screening to rule out the presence of osteomyelitis, meningitis, or metastatic septic foci in the CNS.
7.Known at the time of enrolment to have MRSA bacteremia that is non susceptible to daptomycin AND has a vancomycin MIC >2 mcg/mL
8. 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
9.Previous participation in an anti-infective study during the past 12 months
10.A history of significant hypersensitivity, allergy or intolerance to telavancin. Caution should be taken in subjects with a history of severe hypersensitivity reaction to vancomycin. If the pathogen is known MRSA, allergy to both vancomycin and daptomycin may require exclusion. If the pathogen is known MSSA, allergy to both PCN/cephalosporin and daptomycin may require exclusion. Investigator discretion is advised on a case-by-case basis.
11.Solid organ transplantation or bone marrow transplantation within 6 months before randomization
12.Severe neutropenia, defined as an absolute neutrophil count (ANC) <500 cells per microliter, or expected development of severe neutropenia during study
13.Known or suspected human immunodeficiency (HIV) infection with a CD4+ T-cell count <200/µL within the previous 6 months.
14. Subjects requiring concomitant administration of anti-coagulation therapy (eg, intravenous heparin sodium) AND requiring specific coagulation testing known to have interference by telavancin (prothrombin time/international normalized ratio, activated partial thromboplastin time, or activated clotting time, or coagulation-based Factor X activity assay). Although telavancin does not interfere with coagulation, it interferes with some assays used to monitor coagulation. The use of unfractionated heparin and low molecular weight heparin AND testing using an Anti-Xa chromogenic testing

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare telavancin to standard intravenous therapy (ie, vancomycin, daptomycin, anti-staphylococcal penicillin, or cefazolin) clinical outcomes in the treatment of S. aureus bacteremia including S. aureus right-sided infective endocarditis (SA-RIE);Secondary Objective: - To evaluate the safety and tolerability of telavancin compared with standard intravenous therapy in the treatment of S. aureus bacteremia including SA-RIE<br>- To evaluate the PK profiles of telavancin and vancomycin in subjects with S. aureus bacteraemia, including SA-RIE;Primary end point(s): This study will evaluate: <br>1. Efficacy : Clinical outcome (success or failure) for subjects with CB or RIE in the mAT population <br><br><br><br>;Timepoint(s) of evaluation of this end point: 1. At TOC visit (either 38 (+/-2) days or 52 (+/- 2) days after randomization, depending on the classification of the infection type) in the mAT population.