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

NCT00695903 | Terminated Phase 2 Results DMC

• 2 other identifiers: 3009-013DAP-HDSAB-07-05
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Endocarditis, Bacterial; Infective Endocarditis

Keywords

Gram-positive bacterial infections; Staph Aureus; Bacteremia; MRSA; Infective Endocarditis; Right-sided Infective endocarditis; SABIE; SAIE; RIE

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-emergent Creatine Phosphokinase (CPK) Elevations

  Number of participants with treatment-emergent CPK elevations ≥5 x upper limit of normal (≥1,000 U/L) by the EOT visit.

  On therapy and up to 3 days post-therapy (treatment duration ranged from 2 to 43 days)

• Number of Participants With Elevated Serum Creatinine

  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.

  On therapy and up to 3 days post-therapy (treatment duration ranged from 2 to 43 days)

Secondary Outcomes (2)

• Number of Participants With Treatment Cure at End of Therapy (EOT) Visit

  End of Therapy (median day 12 and 6.5 in daptomycin and vancomycin modified intent-to treat population, respectively)

• Number of Participants With Treatment Cure at Test of Cure (TOC)/Safety Visit

  Test of Cure (TOC) Visit (35 to 49 days post-therapy, approximately week 8)

Study Arms (2)

daptomycin 10 mg/kg

EXPERIMENTAL

Daptomycin 10 mg/kg IV every 24 hours

Drug: daptomycin

vancomycin high-dose

EXPERIMENTAL

Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL

Drug: vancomycin

Interventions

daptomycin DRUG

daptomycin 10 mg/kg IV every 24 hours

Also known as: Cubicin, daptomycin for injection

daptomycin 10 mg/kg

vancomycin DRUG

Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL

Also known as: vancocin

vancomycin high-dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (2)

East Carolina University

Greenville, North Carolina, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Endocarditis, Bacterial; Endocarditis; Gram-Positive Bacterial Infections; Staphylococcal Infections; Bacteremia

Interventions

Daptomycin; Injections; Vancomycin

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Cardiovascular Infections; Cardiovascular Diseases; Heart Diseases; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Drug Administration Routes; Drug Therapy; Therapeutics; Glycopeptides; Glycoconjugates; Carbohydrates

Limitations and Caveats

Because the study was terminated early due to lack of enrollment, there were not sufficient patients to provide meaningful analysis for the following secondary outcomes: persistent/recurrent bacteremia and time to defervescence/clearance.

Results Point of Contact

• Title: Medical Director
• Organization: Cubist Pharmaceuticals

ellie.hershberger@cubist.com

Study Officials

• Peter Pertel, MD

  Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2008
• First Posted: June 12, 2008
• Study Start: September 17, 2008
• Primary Completion: August 24, 2010
• Study Completion: October 1, 2010
• Last Updated: December 24, 2018
• Results First Posted: December 6, 2011

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share

Locations

US (2)