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

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

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.

Study Overview

• Status: Terminated
• Conditions: Endocarditis, Bacterial
• Intervention / Treatment: Drug: Daptomycin

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • NewYork-Presbyterian Hospital, Weill Cornell Campus

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Cubicin
No Intervention: standard of care; Patients with enterococcal endocarditis who elect to receive standard of care therapy as prescribed by their primary physician

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: November 20, 2006
• First Submitted That Met QC Criteria: November 20, 2006
• First Posted (Estimate): November 22, 2006

Study Record Updates

• Last Update Posted (Actual): May 3, 2017
• Last Update Submitted That Met QC Criteria: April 6, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Endocarditis; Daptomycin; Enterococcus
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Cardiovascular Infections; Endocarditis, Bacterial; Endocarditis; Anti-Infective Agents; Anti-Bacterial Agents; Daptomycin
• Other Study ID Numbers: 0507008023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This was a pilot single arm study, for which IPD are not pertinent