Phase 2 Study of Safety, Efficacy, and Pharmacokinetics of Higher Doses of Daptomycin and Vancomycin in MRSA Bacteremia (HDSAB)

This study has been terminated.
(terminated due to lack of enrollment)
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00695903
First received: June 10, 2008
Last updated: November 1, 2011
Last verified: November 2011
  Purpose

The overall goals of this study are to compare the safety and efficacy of daptomycin monotherapy 10 mg/kg/day and vancomycin monotherapy dosed to achieve vancomycin trough levels of 15 to 20 μg/mL for the treatment of methicillin-resistant S. aureus bacteremia (MRSA), including right-sided infective endocarditis (RIE).


Condition Intervention Phase
Endocarditis, Bacterial
Infective Endocarditis
Drug: daptomycin
Drug: vancomycin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Multicenter, Randomized, Double-blinded, Study to Describe the Safety, Efficacy, and Pharmacokinetics of Daptomycin 10 mg/kg/Day and Vancomycin for the Treatment of Methicillin-resistant Staphylococcus Aureus Bacteremia

Resource links provided by NLM:


Further study details as provided by Cubist Pharmaceuticals:

Primary Outcome Measures:
  • Number of Participants With Treatment-emergent Creatine Phosphokinase (CPK) Elevations [ Time Frame: On therapy and up to 3 days post-therapy (treatment duration ranged from 2 to 43 days) ] [ Designated as safety issue: Yes ]
    Number of participants with treatment-emergent CPK elevations ≥5 x upper limit of normal (≥1,000 U/L) by the EOT visit.

  • Number of Participants With Elevated Serum Creatinine [ Time Frame: On therapy and up to 3 days post-therapy (treatment duration ranged from 2 to 43 days) ] [ Designated as safety issue: Yes ]
    Number of participants with treatment-emergent serum creatinine increases ≥0.5 mg/dL (for patients with a baseline value ≤3.0 mg/dL) or ≥1.0 mg/dL (for patients with a baseline value >3.0 mg/dL) by the EOT visit.


Secondary Outcome Measures:
  • Number of Participants With Treatment Cure at End of Therapy (EOT) Visit [ Time Frame: End of Therapy (median day 12 and 6.5 in daptomycin and vancomycin modified intent-to treat population, respectively) ] [ Designated as safety issue: No ]
    Investigator's assessment of treatment cure. Treatment Cure includes successful outcomes of both clinical and microbiological assessments. Clinical cure is defined by clinical improvement of symptoms and signs associated with the underlying infection such that no further anti-infective therapy is required. Microbiological Success is defined by the eradication or presumed eradication of baseline infecting methicillin-resistant S. aureus pathogen and no superinfecting pathogen(s) (Gram-positive) or metastatic methicillin-resistant S. aureus pathogens were isolated post therapy.

  • Number of Participants With Treatment Cure at Test of Cure (TOC)/Safety Visit [ Time Frame: Test of Cure (TOC) Visit (35 to 49 days post-therapy, approximately week 8) ] [ Designated as safety issue: No ]
    Investigator's assessment of clinical response. Treatment Cure includes successful outcomes of both clinical and microbiological assessments. Clinical cure is defined by clinical improvement of symptoms and signs associated with the underlying infection such that no further anti-infective therapy is required. Microbiological Success is defined by the eradication or presumed eradication of baseline infecting methicillin-resistant S. aureus pathogen and no superinfecting pathogen(s) (Gram-positive) or metastatic methicillin-resistant S. aureus pathogens were isolated post therapy.


Enrollment: 38
Study Start Date: September 2008
Study Completion Date: October 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: daptomycin 10 mg/kg
Daptomycin 10 mg/kg IV every 24 hours
Drug: daptomycin
daptomycin 10 mg/kg IV every 24 hours
Other Names:
  • Cubicin
  • daptomycin for injection
Experimental: vancomycin high-dose
Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Drug: vancomycin
Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Other Name: vancocin

Detailed Description:

Patients who meet all inclusion criteria and exhibit none of the exclusion criterial will be randomized to one of two treatment arms:

  1. daptomycin Intravenously (IV) 10 mg/kg every 24 hours
  2. vancomycin IV dosed to maintain trough levels of 15 to 20 μg/mL.

The suggested duration of therapy with daptomycin or vancomycin will be 28 days (or up to 42 days if clinically indicated). Dose adjustments for both drugs will be made by an unblinded pharmacist at each site. To minimize the duration with which patients are treated with antibacterial agents effective against S. aureus prior to enrollment, patients with suspected MRSA bacteremia will be enrolled pending definitive culture results. Suspected MRSA bacteremia will be defined clinically or as initial blood cultures that grow Gram-positive cocci and that were obtained from a patient at increased risk for methicillin-resistant S. aureus infections. However, only patients with confirmed MRSA bacteremia or right-sided infective endocarditis will remain in the study and be evaluated for efficacy. During treatment, regular assessments will be performed. An End-of Therapy (EOT) will be performed 1-3 days after stopping therapy or upon Early Termination (ET). All patients will have a post therapy visit for Test of Cure (TOC) performed 35-49 days following last dose of study drug.

  Eligibility

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

INCLUSION CRITERIA:

  • Written informed consent has been obtained;
  • ≥18 years of age;
  • Suspected MRSA bacteremia determined by clinical judgment or 2 sets of positive blood cultures;
  • Increased risk for an MRSA infection

EXCLUSION CRITERIA:

  • Received >48 hours of vancomycin therapy in the 7 days prior to enrollment;
  • Received any systemic antibacterial agents potentially effective against MRSA in the 7 days prior to enrollment;
  • Anticipated requirement of antibiotics potentially effective against MRSA;
  • High likelihood of left-sided infective endocarditis (LIE);
  • Known/suspected polymicrobial bacteremia or infection including Gram-negative infections;
  • Known pneumonia, osteomyelitis, or meningitis;
  • Intravascular foreign material unless material intended removed within 3 days;
  • Prosthetic heart valve;
  • Cardiac decompensation, valve damage, or both such that high likelihood of valve replacement surgery within first 3 days of study drug treatment;
  • Moribund clinical condition such that death likely within first 3 days of study drug treatment;
  • Shock or hypotension or oliguria unresponsive to fluids after 4 hours;
  • Received investigational drug within 30 days of study entry
  • Received statins or other therapy with associated with rhabdomyolysis within 2 days of study entry;
  • History of significant allergy or intolerance to vancomycin or daptomycin
  • Infecting pathogen with confirmed reduced susceptibility to vancomycin;
  • Infecting pathogen with confirmed reduced susceptibility to daptomycin
  • Creatinine clearance <30 mL/min (Cockcroft-Gault equation actual body weight)
  • Serum creatine phosphokinase (CPK) ≥500 U/L
  • Alanine transaminase (ALT) or aspartate aminotransferase (AST) >5 X ULN;
  • Total bilirubin ≥3.0 mg/dL;
  • Severe neutropenia or expected development severe neutropenia during study;
  • Known or suspected HIV infection with a CD4+ T-cell count <200/μL;
  • Unlikely to comply with study procedures or return for evaluations;
  • Body Mass Index (BMI) ≥40 kg/m2;
  • Pregnant or nursing;
  • Female of childbearing potential not willing to practice barrier methods of birth control.

CONTINUATION CRITERIA:

  • Fulfills A or B or both: A) Confirmed complicated MRSA bacteremia B) Possible or definite RIE caused by MRSA according to modified Duke criteria;
  • Infecting S. aureus strain susceptible to vancomycin;
  • Infecting S. aureus strain susceptible to daptomycin;
  • Appropriate treatment of any foci of infection within first 3 days of study;
  • Removal of any intravascular foreign material not allowed per inclusion criteria within first 3 days of study;
  • Removal of any percutaneous or implanted catheters not allowed per inclusion criteria within first 3 days of study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00695903

Locations
United States, North Carolina
East Carolina University
Greenville, North Carolina, United States
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Cubist Pharmaceuticals
Investigators
Study Director: Peter Pertel, MD Cubist Pharmaceuticals
  More Information

No publications provided

Responsible Party: Cubist Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00695903     History of Changes
Other Study ID Numbers: DAP-HDSAB-07-05
Study First Received: June 10, 2008
Results First Received: August 23, 2011
Last Updated: November 1, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Cubist Pharmaceuticals:
Gram-positive bacterial infections
Staph Aureus
Bacteremia
MRSA
Infective Endocarditis
Right-sided Infective endocarditis
SABIE
SAIE
RIE

Additional relevant MeSH terms:
Bacteremia
Endocarditis
Endocarditis, Bacterial
Bacterial Infections
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Cardiovascular Infections
Vancomycin
Daptomycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014