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

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

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).

Study Overview

• Status: Terminated
• Conditions: Bacteremia
• Intervention / Treatment: Drug: Vancomycin; Drug: Telavancin; Drug: Daptomycin; Drug: Synthetic penicillin; Drug: Cefazolin

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Remington-Davis Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cumberland Pharmaceuticals
• Investigators: Study Director: Medical Monitor, Cumberland Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): April 12, 2018
• Study Completion (Actual): April 12, 2018

Study Registration Dates

• First Submitted: July 31, 2014
• First Submitted That Met QC Criteria: August 1, 2014
• First Posted (Estimate): August 4, 2014

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Bacteremia; Staphylococcus aureus
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Bacteremia; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Cefazolin; Daptomycin; Cloxacillin; Penicillins; Telavancin; Nafcillin; Oxacillin
• Other Study ID Numbers: 0112

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No