Safety and Efficacy of Strategy to Prevent Drug-Induced Nephrotoxicity in High-Risk Patients | RxWiki

Safety and Efficacy of Strategy to Prevent Drug-Induced Nephrotoxicity in High-Risk Patients

Overview[ - collapse ][ - ]

Purpose	For more than fifty years, vancomycin has been cited as a nephrotoxic agent. Reports of vancomycin induced kidney injury (a.k.a vancomycin induced nephrotoxicity or VIN), have waxed and waned throughout the years for various reasons. Recently, VIN has reemerged as a clinical concern. This may be due to various reasons, including new dosing recommendations as well as an increased prevalence of risk factors associated with vancomycin induced nephrotoxicity. This study aims to evaluate a strategy which attempts to reduce kidney damage from vancomycin use.
Condition	Health Care Associated Pneumonia Osteomyelitis/Septic Arthritis Endocarditis Bacteremia Acute Bacterial Skin and Skin Structure Infections
Intervention	Drug: Vancomycin Drug: Ceftaroline Drug: Daptomycin Drug: Linezolid
Phase	Phase 4
Sponsor	Henry Ford Health System
Responsible Party	Henry Ford Health System
ClinicalTrials.gov Identifier	NCT01734694
First Received	November 14, 2012
Last Updated	July 8, 2013
Last verified	July 2013

Tracking Information[ + expand ][ + ]

First Received Date	November 14, 2012
Last Updated Date	July 8, 2013
Start Date	October 2011
Estimated Primary Completion Date	Not Provided
Current Primary Outcome Measures	Nephrotoxicity [Time Frame: Day 1 and daily serum creatinine assessment up to date of discharge] [Designated as safety issue: Yes]Increase in SCr of 0.5 mg/dL or 50% above baseline for at least two consecutive days. This measure will be reported as proportion of patients with nephrotoxicity within each group in relation to the number of patients in each group.
Current Secondary Outcome Measures	Acute Kidney Injury Network Modified Definition of Nephrotoxicity [Time Frame: Day 1 and daily serum creatinine assessment up to date of discharge] [Designated as safety issue: Yes]An abrupt (within 48 hour) reduction in kidney function with one or more of the following 1) Increase in SCr ≥ 0.3 mg/dL 2) Increase SCr ≥ 50% or 3) Decreased urine output (< 0.5 ml/kg/hr x 6 hrs). This measure will be reported as proportion of patients with acute kidney injury within each group in relation to the number of patients in each group. Clinical Success [Time Frame: Daily assessment of signs and symptoms of infection] [Designated as safety issue: No]Clinical success is a composite endpoint of those patients with clinical cure or improvement in clinical signs and symptoms of infection (i.e. SIRS criteria, and microbiology). This measure will be reported as the proportion of patients with clinical success in each group compared to the the total number of patients in the group.

Descriptive Information[ + expand ][ + ]

Brief Title	Safety and Efficacy of Strategy to Prevent Drug-Induced Nephrotoxicity in High-Risk Patients
Official Title	Safety and Efficacy of Strategy to Prevent Drug-Induced Nephrotoxicity in High-Risk Patients
Brief Summary	For more than fifty years, vancomycin has been cited as a nephrotoxic agent. Reports of vancomycin induced kidney injury (a.k.a vancomycin induced nephrotoxicity or VIN), have waxed and waned throughout the years for various reasons. Recently, VIN has reemerged as a clinical concern. This may be due to various reasons, including new dosing recommendations as well as an increased prevalence of risk factors associated with vancomycin induced nephrotoxicity. This study aims to evaluate a strategy which attempts to reduce kidney damage from vancomycin use.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 4
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention
Condition	Health Care Associated Pneumonia Osteomyelitis/Septic Arthritis Endocarditis Bacteremia Acute Bacterial Skin and Skin Structure Infections
Intervention	Drug: Vancomycin Dose optimized vancomycin. Target trough: 15 - 20 mg/L for Health Care Associated Pneumonia, Osteomyelitis, Septic Arthritis, Endocarditis and Bacteremia; Target trough: 10 - 20 mg/L for Acute Bacterial Skin and Skin Structure Infections; Drug: Ceftaroline Dose based on package insert labeling CrCL > 50 mL/min: 600 mg IV q12h CrCL 31-50 mL/min: 400 mg q12h CrCL 15-30 mL/min: 300 mg q12h CrCL < 15mL/min: 200 mg q12h; Other Names: TeflaroDrug: Daptomycin Dose based on renal function and literature dosing recommendations CrCL ≥ 30 mL/min: 6 - 10 mg/kg IV q24h CrCL < 30 mL/min: 6 - 10 mg/kg IV q48h Other Names: CubicinDrug: Linezolid 600 mg IV/PO q12h Other Names: Zyvox
Study Arm (s)	Active Comparator: Vancomycin Active Comparator: Comparator

Recruitment Information[ + expand ][ + ]

Recruitment Status	Terminated
Estimated Enrollment	100
Estimated Completion Date	Not Provided
Estimated Primary Completion Date	September 2013
Eligibility Criteria	Inclusion Criteria: - Aged 18 years or older - Receiving intravenous vancomycin for the treatment of healthcare associated pneumonia, osteomyelitis/septic arthritis, endocarditis/bacteremia, or acute bacterial skin and skin structure infections - Expected to receive vancomycin for at least 72 hours and are within the first 72 hours of therapy - Have at least two or more of the following risk factors for drug-induced nephrotoxicity: a) receipt high-dose vancomycin therapy (greater than or equal to four grams per day) b) receipt of vasopressors c) receipt of nephrotoxic drugs (i.e. aminoglycosides, furosemide, acyclovir, amphotericin b, colistin, and intravenous contrast dye) d) pre-existing renal dysfunction (i.e. SCr greater than or equal to 1.5 mg/dL). Exclusion Criteria: - Pregnancy - End-stage renal disease - Receipt of more than 4 grams of vancomycin prior to enrollment on current admission - Absolute neutrophil count < 1000/mm3
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01734694
Other Study ID Numbers	7089
Has Data Monitoring Committee	Not Provided
Information Provided By	Henry Ford Health System
Study Sponsor	Henry Ford Health System
Collaborators	Not Provided
Investigators	Principal Investigator: Jose Vazquez, M.D. Henry Ford Hospital
Verification Date	July 2013

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