Study of Daptomycin Safety and Efficacy for Complicated Skin and Skin Structure Infections (cSSSI) and Bacteremia in Renal Impairment (RENSE)

This study has been terminated.
(Cubist has reached an agreement with the FDA that enrollment in the DAP-RENSE-08-05 study can stop.)
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals Holdings LLC ( Cubist Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01104662
First received: April 2, 2010
Last updated: April 28, 2015
Last verified: April 2015
Results First Received: April 28, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Single Blind (Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Complicated Skin and Skin Structure Infections
S. Aureus Bacteremia
Renal Impairment
Interventions: Drug: Vancomycin
Drug: Daptomycin
Drug: Semi-Synthetic Penicillin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Daptomycin, Bacteremia, Severe Renal Impairment Cohort 1. Daptomycin was given intravenously 6 milligrams per kilogram (mg/kg) per administration. For bacteremia participants with Creatinine Clearance (CLcr) below 30 milliliters per minute (mL/min) and currently receiving hemodialysis, daptomycin was administered immediately following each hemodialysis session (3 per week) for 14 to 42 days based on disease resolution or Investigator discretion. For participants not receiving dialysis, daptomycin was administered every 48 hours for 14 to 42 days based on disease resolution or Investigator discretion.
Vancomycin or SSP, Bacteremia, Severe Renal Impairment Cohort 1. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin/semi-synthetic penicillin (SSP; for example, nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by Methicillin-Susceptible Staphylococcus Aureus (MSSA) could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator’s discretion. All treatments were dosed per investigator’s discretion and were administered intravenously until end of antibiotic therapy for bacteremia or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Daptomycin, Bacteremia, Moderate Renal Impairment Cohort 2. Daptomycin was given intravenously 6 milligrams per kilogram (mg/kg) per administration. For bacteremia participants with CLcr values between 30 and 50 mL/min not receiving dialysis, daptomycin was administered every 24 hours for 14 to 42 days based on disease resolution or Investigator discretion.
Vancomycin or SSP, Bacteremia, Moderate Renal Impairment Cohort 2. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by MSSA could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator’s discretion. All treatments were dosed per investigator’s discretion and were administered IV until end of antibiotic therapy for bacteremia or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Daptomycin, cSSSI, Severe Renal Impairment Cohort 3. Daptomycin was given intravenously 4 milligrams per kilogram (mg/kg) per administration. For complicated skin and skin structure infections (cSSSI) participants with CLcr below 30 mL/min and currently receiving hemodialysis, daptomycin was administered immediately following each hemodialysis session (3 per week) for 7 to 14 days based on disease resolution or Investigator discretion. For participants not receiving dialysis, daptomycin was administered every 48 hours for 7 to 14 days based on disease resolution or Investigator discretion.
Vancomycin or SSP, cSSSI, Severe Renal Impairment Cohort 3. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by MSSA could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator’s discretion. All treatments were dosed per investigator’s discretion and were administered IV until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Daptomycin, cSSSI, Moderate Renal Impairment Cohort 4. Daptomycin was given intravenously 4 milligrams per kilogram (mg/kg) per administration. For cSSSI participants with CLcr values between 30 and 50 mL/min not receiving dialysis, daptomycin was administered every 24 hours for 7 to 14 days based on disease resolution or Investigator discretion.
Vancomycin or SSP, cSSSI, Moderate Renal Impairment Cohort 4. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by MSSA could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator’s discretion. All treatments were dosed per investigator’s discretion and were administered IV until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.

Participant Flow:   Overall Study
    Daptomycin, Bacteremia, Severe Renal Impairment     Vancomycin or SSP, Bacteremia, Severe Renal Impairment     Daptomycin, Bacteremia, Moderate Renal Impairment     Vancomycin or SSP, Bacteremia, Moderate Renal Impairment     Daptomycin, cSSSI, Severe Renal Impairment     Vancomycin or SSP, cSSSI, Severe Renal Impairment     Daptomycin, cSSSI, Moderate Renal Impairment     Vancomycin or SSP, cSSSI, Moderate Renal Impairment  
STARTED     20     21     5     4     15     16     5     6  
Received at Least 1 Dose of Study Drug     17     17     4     4     15     15     5     6  
COMPLETED     10     11     4     3     14     12     5     6  
NOT COMPLETED     10     10     1     1     1     4     0     0  
Adverse Event                 2                 2                 0                 1                 1                 1                 0                 0  
Clinical Failure                 1                 0                 0                 0                 0                 1                 0                 0  
Participant left investigator’s care                 1                 1                 0                 0                 0                 0                 0                 0  
Reason not specified                 3                 3                 0                 0                 0                 1                 0                 0  
Randomized but not treated                 3                 4                 1                 0                 0                 1                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least 1 dose of study drug.

Reporting Groups
  Description
Daptomycin, Bacteremia, Severe Renal Impairment Cohort 1. Daptomycin was given intravenously 6 milligrams per kilogram (mg/kg) per administration. For bacteremia participants with Creatinine Clearance (CLcr) below 30 milliliters per minute (mL/min) and currently receiving hemodialysis, daptomycin was administered immediately following each hemodialysis session (3 per week) for 14 to 42 days based on disease resolution or Investigator discretion. For participants not receiving dialysis, daptomycin was administered every 48 hours for 14 to 42 days based on disease resolution or Investigator discretion.
Vancomycin or SSP, Bacteremia, Severe Renal Impairment Cohort 1. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by Methicillin-Susceptible Staphylococcus Aureus (MSSA) could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator’s discretion. All treatments were dosed per Investigator’s discretion and were administered intravenously until end of antibiotic therapy for bacteremia or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Daptomycin, Bacteremia, Moderate Renal Impairment Cohort 2. Daptomycin was given intravenously 6 milligrams per kilogram (mg/kg) per administration. For bacteremia participants with CLcr values between 30 and 50 mL/min not receiving dialysis, daptomycin was administered every 24 hours for 14 to 42 days based on disease resolution or Investigator discretion.
Vancomycin or SSP, Bacteremia, Moderate Renal Impairment Cohort 2. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by MSSA could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator’s discretion. All treatments were dosed per Investigator’s discretion and were administered IV until end of antibiotic therapy for bacteremia or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Daptomycin, cSSSI, Severe Renal Impairment Cohort 3. Daptomycin was given intravenously 4 milligrams per kilogram (mg/kg) per administration. For cSSSI participants with CLcr below 30 mL/min and currently receiving hemodialysis, daptomycin was administered immediately following each hemodialysis session (3 per week) for 7 to 14 days based on disease resolution or Investigator discretion. For participants not receiving dialysis, daptomycin was administered every 48 hours for 7 to 14 days based on disease resolution or Investigator discretion.
Vancomycin or SSP, cSSSI, Severe Renal Impairment Cohort 3. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by MSSA could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator’s discretion. All treatments were dosed per Investigator’s discretion and were administered IV until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Daptomycin, cSSSI, Moderate Renal Impairment Cohort 4. Daptomycin was given intravenously 4 milligrams per kilogram (mg/kg) per administration. For cSSSI participants with CLcr values between 30 and 50 mL/min not receiving dialysis, daptomycin was administered every 24 hours for 7 to 14 days based on disease resolution or Investigator discretion.
Vancomycin or SSP, cSSSI, Moderate Renal Impairment Cohort 4. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by MSSA could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator’s discretion. All treatments were dosed per Investigator’s discretion and were administered IV until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.
Total Total of all reporting groups

Baseline Measures
    Daptomycin, Bacteremia, Severe Renal Impairment     Vancomycin or SSP, Bacteremia, Severe Renal Impairment     Daptomycin, Bacteremia, Moderate Renal Impairment     Vancomycin or SSP, Bacteremia, Moderate Renal Impairment     Daptomycin, cSSSI, Severe Renal Impairment     Vancomycin or SSP, cSSSI, Severe Renal Impairment     Daptomycin, cSSSI, Moderate Renal Impairment     Vancomycin or SSP, cSSSI, Moderate Renal Impairment     Total  
Number of Participants  
[units: participants]
  17     17     4     4     15     15     5     6     83  
Age  
[units: participants]
                 
<=18 years     0     0     0     0     0     0     0     0     0  
Between 18 and 65 years     14     12     1     3     11     11     1     3     56  
>=65 years     3     5     3     1     4     4     4     3     27  
Gender  
[units: participants]
                 
Female     7     5     2     2     5     3     3     1     28  
Male     10     12     2     2     10     12     2     5     55  



  Outcome Measures
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1.  Primary:   Number of Participants With Treatment-emergent Creatine Phosphokinase (CPK) Elevations Through End of Therapy/Early Termination (EOT/ET)   [ Time Frame: Baseline through EOT/ET ]

2.  Secondary:   Overall Therapeutic Outcome at Test of Cure (TOC)/Safety Visit   [ Time Frame: Baseline through TOC/Safety Visit ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Vice President, Clinical Research
Organization: Cubist Pharmaceuticals, Inc.
phone: 1.781.860.8660


No publications provided


Responsible Party: Cubist Pharmaceuticals Holdings LLC ( Cubist Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01104662     History of Changes
Other Study ID Numbers: DAP-RENSE-08-05
Study First Received: April 2, 2010
Results First Received: April 28, 2015
Last Updated: April 28, 2015
Health Authority: United States: Food and Drug Administration