Endocarditis, BacterialPhase 2HDSABNCT00695903
Phase 2 Study of Safety, Efficacy, and Pharmacokinetics of Higher Doses of Daptomycin and Vancomycin in MRSA Bacteremia
A Phase 2 study testing daptomycin and vancomycin in people with Endocarditis, Bacterial and Infective Endocarditis, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Endocarditis, Bacterial, Infective Endocarditis
- What is being tested?
- daptomycin and vancomycin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Sep 2008to 1 Oct 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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;
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
East Carolina University
Greenville, North Carolina
About this study
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
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).
Read the detailed description
Patients who meet all inclusion criteria and exhibit none of the exclusion criterial will be randomized to one of two treatment arms:
- daptomycin Intravenously (IV) 10 mg/kg every 24 hours
- 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.
- Conditions
- Endocarditis, Bacterial, Infective Endocarditis
- Being tested
- daptomycin, vancomycin
- Keywords
- Gram-positive bacterial infections, Staph Aureus, Bacteremia, MRSA, Infective Endocarditis, Right-sided Infective endocarditis, SABIE, SAIE, RIE
- Medical subject headings
- Endocarditis, Bacterial, Endocarditis, Gram-Positive Bacterial Infections, Staphylococcal Infections, Bacteremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
daptomycinDrug
Also called Cubicin, daptomycin for injection
daptomycin 10 mg/kg IV every 24 hours
vancomycinDrug
Also called vancocin
Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
| Study group | Role | What they receive |
|---|---|---|
| daptomycin 10 mg/kg | Experimental | Daptomycin 10 mg/kg IV every 24 hours Receives: Drug: daptomycin |
| vancomycin high-dose | Experimental | Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL Receives: Drug: vancomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
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.
Measured: 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
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.
Measured: Test of Cure (TOC) Visit (35 to 49 days post-therapy, approximately week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2008 (estimated)
- Study start17 Sep 2008
- Primary completion24 Aug 2010
- Study completion1 Oct 2010
Why it stopped: terminated due to lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Endocarditis, BacterialStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Peter Pertel, MD, Study director, Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00695903
- Sponsor's protocol ID
- 3009-013
- Other IDs
- DAP-HDSAB-07-05
- Acronym
- HDSAB
- Status last verified
- Dec 2018
- First submitted
- 10 Jun 2008
- Last updated
- 24 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00695903
- Acronym / sponsor ID
- HDSAB / 3009-013
- Conditions
- Endocarditis, Bacterial, Infective Endocarditis
- Keywords
- Gram-positive bacterial infections, Staph Aureus, Bacteremia, MRSA, Infective Endocarditis, Right-sided Infective endocarditis, SABIE, SAIE
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: terminated due to lack of enrollment
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 17 Sep 2008 (actual)
- Primary completion
- 24 Aug 2010 (actual)
- Study completion
- 1 Oct 2010 (actual)
- First posted
- 12 Jun 2008 (estimated)
- Results
- Posted 6 Dec 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Patients who meet all inclusion criteria and exhibit none of the exclusion criterial will be randomized to one of two treatment arms:
- daptomycin Intravenously (IV) 10 mg/kg every 24 hours
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| daptomycin 10 mg/kg | Experimental | Drug: daptomycinDaptomycin 10 mg/kg IV every 24 hours |
| vancomycin high-dose | Experimental | Drug: vancomycinVancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (33 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| daptomycinAlso: Cubicin, daptomycin for injectiondaptomycin 10 mg/kg IV every 24 hours | Drug | daptomycin 10 mg/kg |
| vancomycinAlso: vancocinVancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL | Drug | vancomycin high-dose |
Primary outcome
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)
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)
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.
2 secondary outcomes
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Pertel, MD study director
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing daptomycin and vancomycin in people with Endocarditis, Bacterial and Infective Endocarditis, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Dec 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2018.