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

• ClinicalTrials.gov Identifier: NCT02208063
• Recruitment Status: Terminated
• First Posted: August 4, 2014
• Results First Posted: February 17, 2020
• Last Update Posted: February 17, 2020
• Sponsor: Cumberland Pharmaceuticals
• Information provided by (Responsible Party): Cumberland Pharmaceuticals

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Bacteremia	Drug: Telavancin; Drug: Vancomycin; Drug: Daptomycin; Drug: Synthetic penicillin; Drug: Cefazolin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 121 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 2014
• Actual Primary Completion Date: April 12, 2018
• Actual Study Completion Date: April 12, 2018

Arms and Interventions

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 Name: Cubicin; Drug: Synthetic penicillin; Other Names: Nafcillin; Oxacillin; Cloxacillin; Drug: Cefazolin

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With a Clinical Outcome of Cure at Test of Cure (TOC) [ Time Frame: 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 Outcome Measures :

1. Number of Participants With an Investigator Clinical Outcome of Cure at TOC in the Microbiological All-treated (mAT) Population [ Time Frame: 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
2. Investigator Clinical Response (Success or Failure) at EOT in the Microbiological All-treated (mAT) Population [ Time Frame: 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
3. 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 [ Time Frame: Day 8 ]
   After Day 8, any sign or symptom leading to a subsequent confirmed diagnosis of a new metastatic foci of S. aureus infection

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Ohio

Remington-Davis Clinical Research

Columbus, Ohio, United States, 43215

Sponsors and Collaborators

Cumberland Pharmaceuticals

Investigators

• Study Director: Medical Monitor; Cumberland Pharmaceuticals, Inc.

  Study Documents (Full-Text)

Documents provided by Cumberland Pharmaceuticals:

Study Protocol  [PDF] January 16, 2018

Statistical Analysis Plan  [PDF] April 26, 2018

More Information

• Responsible Party: Cumberland Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02208063
• Other Study ID Numbers: 0112
• First Posted: August 4, 2014
• Results First Posted: February 17, 2020
• Last Update Posted: February 17, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Cumberland Pharmaceuticals:

Bacteremia; Staphylococcus aureus

Additional relevant MeSH terms:

Bacteremia; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Vancomycin; Cefazolin; Daptomycin; Penicillins; Cloxacillin; Oxacillin; Nafcillin; Telavancin; Anti-Bacterial Agents; Anti-Infective Agents