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Phase 4 Efficacy and Safety Study of Cubicin® With and Without Combination Therapy in S. Aureus Infective Endocarditis
This study is currently recruiting participants.
Verified by Cubist Pharmaceuticals, September 2008
Sponsored by: Cubist Pharmaceuticals
Information provided by: Cubist Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00638157
  Purpose

multicenter, randomized, double blind study to describe the safety and efficacy of daptomycin (6 mg/kg q24h) with and without concomitant initial gentamicin combination therapy in the treatment of SAIE


Condition Intervention Phase
Infective Endocarditis
Drug: daptomycin
Drug: daptomycin and gentamicin
Phase IV

MedlinePlus related topics: Endocarditis
Drug Information available for: Gentamicins Daptomycin
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study
Official Title: A Phase 4 Multicenter, Randomized, Double Blind Study to Describe the Efficacy and Safety of Cubicin® (Daptomycin for Injection) With and Without Initial Gentamicin Combination Therapy in the Treatment of S. Aureus Infective Endocarditis

Further study details as provided by Cubist Pharmaceuticals:

Primary Outcome Measures:
  • incidence of adverse events [ Time Frame: 4 Weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Investigator's assessment of clinical response at TOC [ Time Frame: 4 Weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: March 2008
Estimated Study Completion Date: February 2011
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Active Comparator
daptomycin (6 mg/kg q24h)
Drug: daptomycin
6 mg/kg q24h
2: Experimental
daptomycin (6 mg/kg q24h) with concomitant initial gentamicin combination therapy
Drug: daptomycin and gentamicin
daptomycin 6 mg/kg q24h plus initial i.v. gentamicin

Detailed Description:

Patients will be randomized to either of the following two treatment arms:

  • Arm 1: daptomycin
  • Arm 2: daptomycin with initial i.v. gentamicin

Patients who meet all the inclusion criteria and exhibit none of the exclusion criteria may be enrolled. IVDU patients may be randomized and study drug begun on the basis of two separate peripheral blood cultures positive for S. aureus obtained within 96 hours prior to the first dose of study drug.

The recommended minimum duration of treatment for daptomycin will be 28 days. The duration of treatment for gentamicin will be 3 days.

During study treatment, regular assessments (including weekly safety laboratory testing including CPK) will be performed. An End-of-Therapy (EOT) evaluation will be performed on the day of or 1-2 days after completion of daptomycin study drug or upon early termination (ET). All patients will have a post-therapy visit for Test of Cure (TOC)/Safety performed 21-28 days following the last dose of daptomycin study drug.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent has been obtained;
  2. Male or female ≥18 years of age;
  3. IVDU (as confirmed by history of drug abuse within the past 3 months or recent needle track marks);
  4. Definite or possible IE according to the modified Duke Criteria (see Appendix A); [17 ];
  5. Two blood cultures positive for S. aureus obtained within 96 hours prior to first dose of study medication acquired by fresh venipuncture using aseptic technique and analyzed at the local laboratory (see Appendix B).

Exclusion Criteria:

  1. Intravascular foreign material in place at the time that the positive blood culture was drawn (e.g., intracardiac pacemaker wires, percutaneous or implanted venous catheters, vascular grafts), (exception: vascular stents that have been in place for >6 months or permanent pacemaker wires attached via epicardial leads are allowed);
  2. High likelihood of LIE as indicated by:

    1. Prior diagnosis of predisposing left-sided valvular pathology (e.g., rheumatic heart disease, bicuspid aortic valve); or
    2. Findings on screening examination of left-sided valvular pathology (e.g., diastolic murmur of aortic insufficiency); or
    3. Findings on screening examination of major systemic emboli to visceral organs (e.g. cerebral or splenic infarct). Patients may be included if their only findings are consistent with microvascular phenomena due to immune complexes (e.g., splinter hemorrhages, conjunctival petechiae, Roth's spots, Osler's nodes, Janeway's lesions, microhematuria).

    Note: Any patient enrolled in the study that is subsequently found to have LIE may be continued in the trial if determined to be clinically improving by the Investigator.

  3. Prosthetic heart valve;
  4. Baseline Creatinine clearance of <30 mL/min (as calculated by the Cockcroft-Gault equation using actual body weight);
  5. Baseline CPK value 5 X upper limit of normal (ULN) in conjunction with symptoms of myalgia or baseline CPK value 10 X ULN without symptoms;
  6. Alanine aminotransferase (ALT) >5 X ULN;
  7. Aspartate aminotransferase (AST) >5 X ULN;
  8. Moribund clinical condition (i.e. high likelihood of death within 3 days after randomization);
  9. Shock or hypotension (supine systolic blood pressure <80 mm Hg) or oliguria (urine output <20 mL/h) unresponsive to fluids or pressors within 4 hours;
  10. Known pneumonia or osteomyelitis;
  11. Polymicrobial infection or bacteremia due to a pathogen other than S. aureus;
  12. Neutropenia (absolute neutrophil count < 0.5 X 103/μL) and/or lymphopenia (CD4 lymphocytes <0.2X 103/μL);
  13. Anticipated to require non-study antibiotics that may be potentially effective against S. aureus;
  14. Prior gentamicin therapy > 1 day;
  15. Documented history of significant allergy or intolerance to any of the study medications;
  16. Unlikely to comply with study procedures;
  17. Pregnant or nursing. All females with childbearing potential will have a pregnancy test performed at the local laboratory.
  18. Female of childbearing potential and not willing to practice barrier methods of birth control (e.g., condoms or diaphragms together with spermicidal foam or gel) during treatment and for at least 28 days after treatment with study medication
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00638157

Contacts
Contact: Katharin Blackerby (781) 860-8311 katharin.blackerby@cubist.com

Locations
United States, Colorado
Denver Health Medical Center Recruiting
Denver, Colorado, United States, 80204
Principal Investigator: Connie Price, MD            
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Principal Investigator: Marcus Zervos, MD            
Wayne State University Recruiting
Detroit, Michigan, United States, 48201
Principal Investigator: Donald Levine, MD            
United States, Pennsylvania
Temple University School of Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19140
Principal Investigator: Byungse Suh, MD            
Sponsors and Collaborators
Cubist Pharmaceuticals
Investigators
Study Director: Peter Pertel, M.D. Cubist Pharmaceuticals
  More Information

Responsible Party: Cubist Pharmaceuticals ( Katharin Blackerby )
Study ID Numbers: DAP-4IE-06-03
Study First Received: March 12, 2008
Last Updated: December 4, 2008
ClinicalTrials.gov Identifier: NCT00638157  
Health Authority: United States: Food and Drug Administration

Keywords provided by Cubist Pharmaceuticals:
Gram-positive bacterial infections
Staph Aureus
endocarditis
bacteremia
MRSA

Study placed in the following topic categories:
Bacterial Infections
Heart Diseases
Bacteremia
Bacterial endocarditis
Endocarditis
Daptomycin
Staphylococcal Infections
Gram-Positive Bacterial Infections
Endocarditis, Bacterial
Infective endocarditis
Endocarditis, infective
Gentamicins
Cardiovascular Infections

Additional relevant MeSH terms:
Protein Synthesis Inhibitors
Anti-Infective Agents
Anti-Bacterial Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Enzyme Inhibitors
Cardiovascular Diseases
Infection
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009