Daptomycin as an Adjuvant Agent in the Treatment of Enterococcal Native Valve Endocarditis.

• ClinicalTrials.gov Identifier: NCT00401960
• Recruitment Status: Terminated
• First Posted: November 22, 2006
• Results First Posted: May 3, 2017
• Last Update Posted: May 3, 2017
• Sponsor: Weill Medical College of Cornell University
• Information provided by (Responsible Party): Rhee, Kyu Y., Weill Medical College of Cornell University

Study Description

Brief Summary:

The aim of this study is to determine the safety and efficacy of daptomycin when used as an adjuvant agent to standard care in the treatment of proven native valve Enterococcal endocarditis. Patients with this disease will be offered the option of receiving daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving. The hypothesis of this study is that daptomycin added to standard therapy for Enterococcal endocarditis is safe and efficacious.

Patients who receive daptomycin + standard therapy will be compared to patients who receive standard therapy alone with respect to the following outcomes:

1. Safety.

   1. The frequency of any Grade 3 or 4 toxicity (DAIDS scale) will be measured.
   2. The frequency of muscle toxicity or renal toxicity, as determined by predefined criteria.

2. Efficacy.

   1. Clinical efficacy.

      • Time to clearance of bacteremia
      • Cure at 6 weeks following completion of antibiotic therapy
      • Mortality at 6 weeks following completion of antibiotic therapy

   2. Microbiologic efficacy.

      • Peak and trough serum bactericidal titers
      • The minimum bactericidal concentration of Enterococci to daptomycin

We expect to enroll 40 patients over 2 years.

Condition or disease	Intervention/treatment	Phase
Endocarditis, Bacterial	Drug: Daptomycin	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label Study to Assess the Efficacy and Safety of Daptomycin in Combination With Anti-Cell Wall Active Therapy in the Treatment of Enterococcal Endocarditis
• Study Start Date: September 2006
• Actual Primary Completion Date: October 2008
• Actual Study Completion Date: October 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Daptomycin adjunctive group; Patients with enterococcal endocarditis who elect to receive daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving	Drug: Daptomycin; daptomycin at a dose of 8 milligrams/kilogram/day in addition to the antibiotics they are already receiving for native valve enterococcal endocarditis; Other Name: Cubicin
No Intervention: standard of care; Patients with enterococcal endocarditis who elect to receive standard of care therapy as prescribed by their primary physician

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Any Grade 3 or 4 Toxicity (DAIDS Scale) [ Time Frame: weekly ]
   Number of Participants any Grade 3 or 4 toxicity (DAIDS scale); please see adverse event table for details
2. Number of Participants With Muscle Toxicity or Renal Toxicity, as Determined by Predefined Criteria [ Time Frame: weekly ]
   Number of Participants with creatine kinase elevation > 3x upper limit of normal or elevations of serum Cr >= 30% above baseline

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:

• Age 18 or over
• Definite Enterococcal endocarditis, as defined by modified Duke criteria
• Able to complete follow-up 3 and 6 weeks following completion of intravenous antibiotic therapy

Exclusion Criteria:

• Pregnancy or breast feeding
• Creatine phosphokinase levels over two times the upper limit of normal
• Renal insufficiency or dialysis requirement.
• Presence of chronic indwelling bloodstream catheters or foreign body devices suspected as primary or secondary sites of enterococcal infection unamenable to removal or replacement
• Inability to discontinue or abstain from use of a HMG CoA reductase inhibitor during the study period.
• Hypersensitivity to any of the study medications.
• Any condition that, in the investigator's opinion, may interfere with protocol compliance including, but not limited to, active substance abuse and/or dementia.
• Prosthetic valve endocarditis

Contacts and Locations

Locations

United States, New York

NewYork-Presbyterian Hospital, Weill Cornell Campus

New York, New York, United States, 10021

Sponsors and Collaborators

Weill Medical College of Cornell University

Investigators

• Principal Investigator: Kyu Y Rhee, MD, PhD; Weill Medical College of Cornell University

More Information

• Responsible Party: Rhee, Kyu Y., Assistant Professor, Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT00401960 History of Changes
• Other Study ID Numbers: 0507008023
• First Posted: November 22, 2006
• Results First Posted: May 3, 2017
• Last Update Posted: May 3, 2017
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: This was a pilot single arm study, for which IPD are not pertinent

Keywords provided by Rhee, Kyu Y., Weill Medical College of Cornell University:

Enterococcus; Daptomycin; Endocarditis

Additional relevant MeSH terms:

Endocarditis, Bacterial; Endocarditis; Heart Diseases; Cardiovascular Diseases; Bacterial Infections; Cardiovascular Infections; Infection; Daptomycin; Anti-Bacterial Agents; Anti-Infective Agents