Infective EndocarditisPhase 4NCT00638157
Phase 4 Efficacy and Safety Study of Cubicin® With and Without Combination Therapy in S. Aureus Infective Endocarditis (SAIE)
A Phase 4 study testing daptomycin and daptomycin and gentamicin in people with Infective Endocarditis, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 4 sites in United States.
Trial summary
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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infective Endocarditis
- What is being tested?
- daptomycin and daptomycin and gentamicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 4 sitesUnited States
- Study dates
- 13 Feb 2009to 9 Nov 2011
- Phase
- Phase 4
- 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;
- Male or female ≥18 years of age;
- IVDU (as confirmed by history of drug abuse within the past 3 months or recent needle track marks);
- Definite or possible IE according to the modified Duke Criteria (see Appendix A); [17 ];
- 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).
Who cannot join
- 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);
- High likelihood of LIE as indicated by:
- Prior diagnosis of predisposing left-sided valvular pathology (e.g., rheumatic heart disease, bicuspid aortic valve); or
- Findings on screening examination of left-sided valvular pathology (e.g., diastolic murmur of aortic insufficiency); or
- 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.
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- Prosthetic heart valve;
- Baseline Creatinine clearance of <30 mL/min (as calculated by the Cockcroft-Gault equation using actual body weight);
- 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;
- Alanine aminotransferase (ALT) >5 X ULN;
- Aspartate aminotransferase (AST) >5 X ULN;
- Moribund clinical condition (i.e. high likelihood of death within 3 days after randomization);
- 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;
- Known pneumonia or osteomyelitis;
- Polymicrobial infection or bacteremia due to a pathogen other than S. aureus;
- Neutropenia (absolute neutrophil count < 0.5 X 103/μL) and/or lymphopenia (CD4 lymphocytes <0.2X 103/μL);
- Anticipated to require non-study antibiotics that may be potentially effective against S. aureus;
- Prior gentamicin therapy > 1 day;
- Documented history of significant allergy or intolerance to any of the study medications;
- Unlikely to comply with study procedures;
- Pregnant or nursing. All females with childbearing potential will have a pregnancy test performed at the local laboratory.
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Denver Health Medical Center
Denver, Colorado, 80204
Wayne State University
Detroit, Michigan, 48201
Henry Ford Health System
Detroit, Michigan, 48202
Temple University School of Medicine
Philadelphia, Pennsylvania, 19140
About this 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
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
Read the 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. Intravenous drug user (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.
- Conditions
- Infective Endocarditis
- Being tested
- daptomycin, daptomycin and gentamicin
- Keywords
- Gram-positive bacterial infections, Staph Aureus, endocarditis, bacteremia, methicillin-resistant Staphylococcus aureus (MRSA)
- Medical subject headings
- 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
Intravenous (i.v.) 6 mg/kg q24h
daptomycin and gentamicinDrug
Also called Cubicin, daptomycin for injection, gentamicin
i.v. daptomycin 6 mg/kg q24h plus initial i.v. gentamicin
| Study group | Role | What they receive |
|---|---|---|
| Daptomycin Alone | Active comparator | daptomycin 6 mg/kg q24h for treatment of right-sided infective endocarditis Receives: Drug: daptomycin |
| Daptomycin plus gentamicin | Experimental | daptomycin 6 mg/kg q24h with concomitant initial gentamicin dosed for the first 2 days of therapy for the treatment of right-sided infective endocarditis Receives: Drug: daptomycin and gentamicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Summary of Clinically Significant Increases in Serum Creatinine by Visit
The End of Treatment (EOT)/Early Termination (ET) visit occurred on the day that therapy was stopped or up to 2 days after the last dose of daptomycin. The Test of Cure (TOC)/Safety visit occurred 21 to 28 days after the last dose of daptomycin therapy. The overall median duration of treatment was 13.0 days in both the daptomycin group and the combination therapy group. The definition of elevated serum creatinine at baseline is >3.0 mg/dL, and not elevated is ≤3.0 mg/dL. Clinically significant increases in serum creatinine is defined as an increase ≥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.
Measured: Baseline, EOT Visit, TOC
Secondary outcomes (1)
Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
TOC/Safety visit occurred 21 to 28 days after the last dose of daptomycin therapy. Clinical response was assessed by the investigator as cure, improvement, failure, and unable to evaluate. Microbiological response, which was determined by the sponsor based on review of baseline and post-baseline culture results, included success, failure, and nonevaluable. TC=Treatment Cure; TF=Treatment Failure; TI=Treatment Improved.
Measured: TOC Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2008 (estimated)
- Study start13 Feb 2009
- Primary completion9 Nov 2011
- Study completion9 Nov 2011
Why it stopped: commitment completed
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 Infective EndocarditisStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 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
- Paula Bokesch, M.D., Study director, Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00638157
- Sponsor's protocol ID
- 3009-010
- Other IDs
- DAP-4IE-06-03
- Status last verified
- Jan 2021
- First submitted
- 12 Mar 2008
- Last updated
- 2 Feb 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- 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 2 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00638157
- Acronym / sponsor ID
- 3009-010
- Conditions
- Infective Endocarditis
- Keywords
- Gram-positive bacterial infections, Staph Aureus, endocarditis, bacteremia, methicillin-resistant Staphylococcus aureus (MRSA)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: commitment completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 13 Feb 2009 (actual)
- Primary completion
- 9 Nov 2011 (actual)
- Study completion
- 9 Nov 2011 (actual)
- First posted
- 18 Mar 2008 (estimated)
- Results
- Posted 22 May 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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. Intravenous drug user (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Daptomycin Alone | Active comparator | Drug: daptomycindaptomycin 6 mg/kg q24h for treatment of right-sided infective endocarditis |
| Daptomycin plus gentamicin | Experimental | Drug: daptomycin and gentamicindaptomycin 6 mg/kg q24h with concomitant initial gentamicin dosed for the first 2 days of therapy for the treatment of right-sided infective endocarditis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Written informed consent has been obtained;
- Male or female ≥18 years of age;
- IVDU (as confirmed by history of drug abuse within the past 3 months or recent needle track marks);
- Definite or possible IE according to the modified Duke Criteria (see Appendix A); [17 ];
- 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).
Key exclusion criteria (22 listed)
- 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);
- High likelihood of LIE as indicated by:
- 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.
- Prosthetic heart valve;
- Baseline Creatinine clearance of <30 mL/min (as calculated by the Cockcroft-Gault equation using actual body weight);
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 injectionIntravenous (i.v.) 6 mg/kg q24h | Drug | Daptomycin Alone |
| daptomycin and gentamicinAlso: Cubicin, daptomycin for injection, gentamicini.v. daptomycin 6 mg/kg q24h plus initial i.v. gentamicin | Drug | Daptomycin plus gentamicin |
Primary outcome
Summary of Clinically Significant Increases in Serum Creatinine by Visit
Time frame: Baseline, EOT Visit, TOC
The End of Treatment (EOT)/Early Termination (ET) visit occurred on the day that therapy was stopped or up to 2 days after the last dose of daptomycin. The Test of Cure (TOC)/Safety visit occurred 21 to 28 days after the last dose of daptomycin therapy. The overall median duration of treatment was 13.0 days in both the daptomycin group and the combination therapy group. The definition of elevated serum creatinine at baseline is >3.0 mg/dL, and not elevated is ≤3.0 mg/dL. Clinically significant increases in serum creatinine is defined as an increase ≥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.
1 secondary outcome
Summary of the Investigator's Assessment of Clinical Response at the TOC Visit
Time frame: TOC Visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2021.
- 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.
Paula Bokesch, M.D. study director
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing daptomycin and daptomycin and gentamicin in people with Infective Endocarditis, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 4 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 5 inclusion and 22 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 2 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 22 May 2013). 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?
Summary of Clinically Significant Increases in Serum Creatinine by Visit (time frame: Baseline, EOT Visit, TOC). 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 2 Feb 2021.