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
ClinicalTrials.gov Identifier:
NCT01104662
First received: April 2, 2010
Last updated: October 9, 2012
Last verified: October 2012
  Purpose

This is a multicenter, randomized, evaluator-blinded, comparator-controlled study. 1:1 randomization daptomycin or comparator, stratified by degree of renal impairment [creatinine clearance(CLcr) 30 - 50 mL/min and <30 mL/min] and by type of infection [bacteremia and complicated Skin and Skin Structure Infections (cSSSI)] to create 4 cohorts defined as follows:

  1. Bacteremia and CLcr <30 mL/min
  2. Bacteremia and CLcr 30 - 50 mL/min
  3. cSSSI and CLcr <30 mL/min
  4. cSSSI and CLcr 30 - 50 mL/min

Patients will be treated and evaluated for safety, microbiological and clinical efficacy in accordance with their type of infection and degree of renal impairment. Peak and trough samples will be collected to assess exposure to daptomycin for patients on Day 1 and following the 5th dose.


Condition Intervention Phase
Complicated Skin and Skin Structure Infections
S. Aureus Bacteremia
Renal Impairment
Drug: Vancomycin
Drug: Daptomycin 7-14 days moderate renal impairment
Drug: Daptomycin 7 - 14 days severe renal impairment, hemodialysis
Drug: Daptomycin 7 - 14 days severe renal impairment no hemodialysis
Drug: Daptomycin 14 - 42 days, moderate renal impairment
Drug: Daptomycin 14 - 42 days, severe renal impairment on hemodialysis
Drug: Daptomycin 14 - 42 days severe renal impairment, no hemodialysis
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prospective Multicenter Randomized Evaluator-blinded Comparator-controlled Study to Describe the Safety and Efficacy of Daptomycin for the Treatment of cSSSI and Staphylococcus Aureus Bacteremia Among Subjects With Renal Impairment

Resource links provided by NLM:


Further study details as provided by Cubist Pharmaceuticals:

Primary Outcome Measures:
  • Incidence of treatment-emergent Creatine Phosphokinase (CPK)elevations through End of Therapy/Early Termination (EOT/ET) [ Time Frame: average 3 to 6 weeks following first dose of study drug ] [ Designated as safety issue: Yes ]
    Incidence of treatment-emergent CPK elevations >500 U/L above baseline at any time from Day 1 through the EOT/ET visit


Secondary Outcome Measures:
  • Overall therapeutic outcome at Test of Cure (TOC)/Safety Visit [ Time Frame: average 4 to 8 weeks following first dose of study drug ] [ Designated as safety issue: No ]
    Sponsor defined therapeutic outcome at the TOC/Safety visit. Therapeutic outcome is the combined clinical and microbiological response of the subject's infection (e.g. cure, improvement, failure).


Enrollment: 92
Study Start Date: April 2010
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Vancomyin +/- SSP cSSSI
Vancomycin plus or minus semi-synthetic penicillin (SSP) for treatment of complicated skin and skin structure infections
Drug: Vancomycin
vancomycin dosed according to local standard of care for 7-14 days
Experimental: Daptomycin cSSSI
Daptomycin 4 mg/kg for treatment of complicated skin and skin structure infections
Drug: Daptomycin 7-14 days moderate renal impairment
daptomycin 4 mg/kg q24h
Drug: Daptomycin 7 - 14 days severe renal impairment, hemodialysis
daptomycin 4 mg/kg 3X/week
Drug: Daptomycin 7 - 14 days severe renal impairment no hemodialysis
daptomycin 4 mg/kg every 48 hours
Active Comparator: Vancomycin +/- SSP bacteremia
Vancomycin plus or minus Semi-synthetic Penicillin for the treatment of bacteremia
Drug: Vancomycin
Vancomycin dosed according to standard of care for 14-42 days
Experimental: Daptomycin Bacteremia
Daptomycin 6 mg/kg for the treatment of bacteremia
Drug: Daptomycin 14 - 42 days, moderate renal impairment
daptomycin 6 mg/kg every 24 hours
Drug: Daptomycin 14 - 42 days, severe renal impairment on hemodialysis
daptomycin 6 mg/kg 3x/week
Drug: Daptomycin 14 - 42 days severe renal impairment, no hemodialysis
daptomycin 6 mg/kg every 48 hours

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Male or female ≥ 18 years of age
  • Diagnosis of cSSSI or S. aureus bacteremia
  • Renal impairment of CLcr of 30 - 50 mL/min or CLcr <30 mL/min per Cockcroft-Gault equation using actual body weight;
  • Functioning hemodialysis access and on stable regimen for those receiving dialysis;
  • In appropriate health for the study with no acute or chronic illnesses that could adversely impact safety or ability to complete the study.

Specific inclusion criteria for cSSSI:

  • Presence of a wound infection, major abscess, severe carbunculosis, infected ulcers, dialysis access site infection, or other type of infection in presence of complicating factor.
  • At least 3 of the following symptoms, signs, or laboratory values of a skin infection: elevated temperature; elevated white blood cell (WBC) count; Pain; Tenderness; Swelling; Erythema greater than 1 cm beyond wound edge; Induration; Pus formation;
  • Evidence of a Gram-positive infecting pathogen as indicated by positive Gram stain or culture obtained within 48 hours prior to study drug administration
  • Infection of sufficient severity to require parenteral antimicrobial therapy.

Specific inclusion criteria for S. aureus bacteremia:

  • Documented S. aureus bacteremia defined as at least one positive blood culture for S. aureus obtained within 96 hours prior to the first dose of study medication

Exclusion Criteria:

  • Pregnant or lactating females, or unwilling to practice barrier methods of birth control
  • Received an investigational drug (including experimental biologic agents) within 30 days of study entry;
  • Unable to discontinue use of HMG-CoA reductase inhibitor therapy while on study;
  • Known allergy or intolerance to daptomycin, penicillin, or vancomycin;
  • Active I.V. drug abuse;
  • Confirmed or suspected osteomyelitis, septic arthritis, meningitis, epidural abscess, intra-abdominal infection, pneumonia, or infective endocarditis;
  • Required use of non-study systemic antibacterial agent with activity against target pathogen;
  • History of muscular disease;
  • Neurological disease except stroke >6 months prior to study entry;
  • Intramuscular injection within 7 days of study drug administration;
  • Moribund clinical condition (high likelihood of death during next 3 days);
  • Shock or hypotension (supine systolic blood pressure <80 mmHg);
  • Body mass index (BMI) <18 or >40 kg/m2 [BMI = weight (kg)/height (m2)]
  • Known HIV infection with CD4 count ≤200 cells/mm3;
  • Neutropenic subjects with an absolute neutrophil count ≤500 cells/mm3;
  • Anticipated to develop neutropenia absolute neutrophil count ≤500 due to prior or planned chemotherapy;
  • Alanine aminotransferase (ALT) value >3 × upper limit of normal (ULN);
  • Aspartate aminotransferase (AST) value >3 × ULN;
  • Total bilirubin values ≥ 1.5 x ULN associated with ALT values >3 x ULN;
  • Creatine phosphokinase (CPK) value >2 × ULN;
  • Hemoglobin <8 gm/dL;
  • Unlikely to comply with study procedures or to return for evaluations;
  • History of rhabdomyolysis;
  • Prior enrollment into this study;
  • Infections caused by Gram-positive pathogens known to be resistant to daptomycin or selected comparator agent.

Specific exclusion criteria for cSSSI:

  • Minor or superficial skin infections as the primary site of infection;
  • Cellulitis or erysipelas not associated with complicating factor as primary site of infection;
  • Perirectal abscess, hidradenitis suppurativa, concomitant gangrene, myositis, multiple infected ulcers at distant sites, necrotizing fasciitis, or infected third-degree burn wounds;
  • Infections requiring emergency surgery;
  • Infections suspected or documented to be due exclusively to gram-negative, anaerobic, or fungal organism;
  • Confirmed or suspected disorder that could interfere with the evaluations (e.g., primary skin disorders);
  • Use of a topical antibiotic at the site of the infection;
  • Use of systemic antibacterial therapy for the infection for >24 hours within 48 hours prior to start of study drug unless (a) infecting Gram-positive pathogen resistant to therapy or (b) therapy administered for 3 or more days with worsening or no improvement;
  • Planned surgical treatment that is considered curative of the infection.

Specific exclusion criteria for S. aureus bacteremia:

  • Has intravascular foreign material at the time the positive blood culture was drawn (e.g., intracardiac pacemaker wires, percutaneous or implanted venous catheters, vascular grafts) unless material removed within 4 days after first dose of study medication or approval of medical monitor (exceptions: vascular stents in place for > 6 months, permanent pacemaker attached via epicardial leads, or any dialysis access device unless this material is felt to be infected);
  • Prosthetic heart valve;
  • Cardiac decompensation or valve damage or both with high likelihood of valve surgery in the 3 days after randomization;
  • Polymicrobial blood infection.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01104662

Locations
United States, California
Azusa, California, United States
Los Angeles, California, United States
Torrance, California, United States
United States, District of Columbia
Washington, District of Columbia, United States
United States, Georgia
Decatur, Georgia, United States
United States, New Jersey
Somers Point, New Jersey, United States
United States, North Carolina
Winston-Salem, North Carolina, United States
United States, Ohio
Columbus, Ohio, United States
United States, Pennsylvania
West Reading, Pennsylvania, United States
United States, Texas
Mission, Texas, United States
Sponsors and Collaborators
Cubist Pharmaceuticals
Investigators
Study Director: Ellie Hershberger, Pharm.D. Cubist Pharmaceuticals
  More Information

No publications provided

Responsible Party: Cubist Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01104662     History of Changes
Other Study ID Numbers: DAP-RENSE-08-05
Study First Received: April 2, 2010
Last Updated: October 9, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Daptomycin
Infection
Communicable Diseases
Renal Insufficiency
Bacteremia
Kidney Diseases
Urologic Diseases
Bacterial Infections
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014