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

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ClinicalTrials.gov Identifier: NCT00695903
Recruitment Status : Terminated (terminated due to lack of enrollment)
First Posted : June 12, 2008
Results First Posted : December 6, 2011
Last Update Posted : March 24, 2017
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Endocarditis, Bacterial
Infective Endocarditis
Interventions Drug: daptomycin
Drug: vancomycin
Enrollment 38

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Daptomycin 10 mg/kg Vancomycin High-dose
Hide Arm/Group Description Daptomycin 10 mg/kg Intravenously (IV) every 24 hours Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Period Title: Had End of Therapy (EOT) Assessment
Started 19 19
Met Continuation Criteria 9 6
Completed 7 4
Not Completed 12 15
Reason Not Completed
Randomized not treated             0             2
No confirmed MRSA             9             9
Adverse Event             1             0
Withdrawal by Subject             1             1
Physician Decision             0             1
Protocol Violation             1             2
Period Title: Had Test of Cure (TOC) Assessment
Started 7 4
Completed 5 3
Not Completed 2 1
Reason Not Completed
Lack of Efficacy             1             0
Lost to Follow-up             1             0
Adverse Event             0             1
Arm/Group Title Daptomycin 10 mg/kg Vancomycin High-dose Total
Hide Arm/Group Description Daptomycin 10 mg/kg Intravenously (IV) every 24 hours Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL Total of all reporting groups
Overall Number of Baseline Participants 19 17 36
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 17 participants 36 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
16
  84.2%
15
  88.2%
31
  86.1%
>=65 years
3
  15.8%
2
  11.8%
5
  13.9%
[1]
Measure Description: Safety Population. Two patients in the high-dose vancomycin arm were randomized but not treated and therefore not included in the safety population.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 17 participants 36 participants
Female
6
  31.6%
4
  23.5%
10
  27.8%
Male
13
  68.4%
13
  76.5%
26
  72.2%
[1]
Measure Description: Safety Population. Two patients in the high-dose vancomycin arm were randomized but not treated and therefore not included in the safety population.
1.Primary Outcome
Title Number of Participants With Treatment-emergent Creatine Phosphokinase (CPK) Elevations
Hide Description Number of participants with treatment-emergent CPK elevations ≥5 x upper limit of normal (≥1,000 U/L) by the EOT visit.
Time Frame On therapy and up to 3 days post-therapy (treatment duration ranged from 2 to 43 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least one dose of study medication (Safety Population). Two patients in the high-dose vancomycin arm were randomized but not treated and therefore not included in the safety population.
Arm/Group Title Daptomycin 10 mg/kg Vancomycin High-dose
Hide Arm/Group Description:
Daptomycin 10 mg/kg Intravenously (IV) every 24 hours
Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Overall Number of Participants Analyzed 19 17
Measure Type: Number
Unit of Measure: Participants
2 0
2.Primary Outcome
Title Number of Participants With Elevated Serum Creatinine
Hide Description 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.
Time Frame On therapy and up to 3 days post-therapy (treatment duration ranged from 2 to 43 days)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least one dose of study medication (Safety Population). Two patients in the high-dose vancomycin arm were randomized but not treated and therefore not included in the safety population.
Arm/Group Title Daptomycin 10 mg/kg Vancomycin High-dose
Hide Arm/Group Description:
Daptomycin 10 mg/kg Intravenously (IV) every 24 hours
Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Overall Number of Participants Analyzed 19 17
Measure Type: Number
Unit of Measure: participants
0 4
3.Secondary Outcome
Title Number of Participants With Treatment Cure at End of Therapy (EOT) Visit
Hide Description 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.
Time Frame End of Therapy (median day 12 and 6.5 in daptomycin and vancomycin modified intent-to treat population, respectively)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients who met the continuation criteria (modified intent-to-treat) and had a EOT assessment of clinical outcome.
Arm/Group Title Daptomycin 10 mg/kg Vancomycin High-dose
Hide Arm/Group Description:
Daptomycin 10 mg/kg Intravenously (IV) every 24 hours
Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Overall Number of Participants Analyzed 7 4
Measure Type: Number
Unit of Measure: participants
6 3
4.Secondary Outcome
Title Number of Participants With Treatment Cure at Test of Cure (TOC)/Safety Visit
Hide Description 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.
Time Frame Test of Cure (TOC) Visit (35 to 49 days post-therapy, approximately week 8)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Subset of modified intent-to-treat population who completed TOC/Safety visit
Arm/Group Title Daptomycin 10 mg/kg Vancomycin High-dose
Hide Arm/Group Description:
Daptomycin 10 mg/kg Intravenously (IV) every 24 hours
Vancomycin 15 mg/kg IV, dosed to maintain trough serum concentrations of 15 to 20 μg/mL
Overall Number of Participants Analyzed 5 3
Measure Type: Number
Unit of Measure: participants
5 3
Time Frame Safety assessments were performed throughout the study (an average of 8 weeks). Safety assessments were conducted at the EOT/Early Termination visit (on the day of or within 3 days after therapy was stopped) and TOC visit (35 to 49 days post-therapy).
Adverse Event Reporting Description On therapy safety assessments included maximum daily temperature, vital signs, physical examination and clinical laboratory tests. Investigators were required to report lab abnormalities (e.g. CPK, serum creatinine) as adverse events only when he/she considered the abnormality clinically significant.
 
Arm/Group Title Daptomycin Vancomycin
Hide Arm/Group Description Daptomycin 10 mg/kg i.v.q24hr Vancomycin 15 mg/kg i.v., dosed to maintain trough serum concentrations of 15 to 20 ug/mL
All-Cause Mortality
Daptomycin Vancomycin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Daptomycin Vancomycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/19 (15.79%)      4/17 (23.53%)    
Cardiac disorders     
Atrioventricular block complete  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Congenital, familial and genetic disorders     
Atrial septal defect  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Diarrhoea  1  2/19 (10.53%)  2 0/17 (0.00%)  0
Nausea  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Pancreatitis acute  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Vomiting  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Infections and infestations     
Endocarditis bacterial  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Osteomyelitis  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Renal and urinary disorders     
Renal failure  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Renal failure acute  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Daptomycin Vancomycin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/19 (31.58%)      10/17 (58.82%)    
Eye disorders     
Diplopia  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Photophobia  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Gastrointestinal disorders     
Abdominal discomfort  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Constipation  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Diarrhoea  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Nausea  1  0/19 (0.00%)  0 1/17 (5.88%)  1
General disorders     
Catheter related complication  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Catheter site discharge  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Catheter site erythema  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Catheter site haemorrhage  1  1/19 (5.26%)  2 0/17 (0.00%)  0
Catheter site oedema  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Catheter site pain  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Catheter site related reaction  1  1/19 (5.26%)  3 0/17 (0.00%)  0
Pain  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Infections and infestations     
Pneumonia bacterial  1  0/19 (0.00%)  0 1/17 (5.88%)  2
Urinary tract infection bacterial  1  0/19 (0.00%)  0 1/17 (5.88%)  2
Vulvovaginal mycotic infection  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Investigations     
Blood creatine phosphokinase increased  1  2/19 (10.53%)  2 0/17 (0.00%)  0
Metabolism and nutrition disorders     
Hyperphosphataemia  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Hypocalcaemia  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Hypoglycaemia  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Hypomagnesaemia  1  1/19 (5.26%)  1 2/17 (11.76%)  2
Musculoskeletal and connective tissue disorders     
Back pain  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Neck pain  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Pain in extremity  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Nervous system disorders     
Headache  1  1/19 (5.26%)  1 1/17 (5.88%)  1
Hypoaesthesia  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Paraesthesia  1  1/19 (5.26%)  1 0/17 (0.00%)  0
Renal and urinary disorders     
Renal failure acute  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Skin and subcutaneous tissue disorders     
Pruritus  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Rash  1  0/19 (0.00%)  0 2/17 (11.76%)  2
Skin exfoliation  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Vascular disorders     
Hypertension  1  0/19 (0.00%)  0 1/17 (5.88%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first publication is initiated by Cubist. If first publication not published within 1 year of study conclusion or termination, Investigator has right to publish and disclose the data. Prior to any submission for publication, presentation, or communication of results or information arising from the study, Investigator shall provide Cubist at least 90 days for review and comment upon the manuscript or other material for such publication or presentation.
Results Point of Contact
Name/Title: Medical Director
Organization: Cubist Pharmaceuticals
Responsible Party: Cubist Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT00695903     History of Changes
Other Study ID Numbers: 3009-013
DAP-HDSAB-07-05 ( Other Identifier: Cubist Study Number )
First Submitted: June 10, 2008
First Posted: June 12, 2008
Results First Submitted: August 23, 2011
Results First Posted: December 6, 2011
Last Update Posted: March 24, 2017