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

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	Intervention	Phase
Health Care Associated Pneumonia Osteomyelitis/Septic Arthritis Endocarditis Bacteremia Acute Bacterial Skin and Skin Structure Infections	Drug: Vancomycin Drug: Ceftaroline Drug: Daptomycin Drug: Linezolid	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: Prevention
Official Title:	Safety and Efficacy of Strategy to Prevent Drug-Induced Nephrotoxicity in High-Risk Patients

Resource links provided by NLM:

MedlinePlus related topics: Endocarditis Pneumonia

Drug Information available for: Vancomycin Vancomycin hydrochloride Daptomycin Linezolid Ceftaroline Ceftaroline fosamil

U.S. FDA Resources

Further study details as provided by Henry Ford Health System:

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.

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.

Estimated Enrollment:	130
Study Start Date:	October 2011
Estimated Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Vancomycin	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;
Active Comparator: Comparator	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 Name: Teflaro Drug: 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 Name: Cubicin Drug: Linezolid 600 mg IV/PO q12h Other Name: Zyvox

Arms

Assigned Interventions

Active Comparator: Vancomycin

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;

Active Comparator: Comparator

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 Name: Teflaro

Drug: 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 Name: Cubicin

Drug: Linezolid

600 mg IV/PO q12h

Other Name: Zyvox

Eligibility

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01734694

Contacts

Contact: Joseph Carreno, Pharm.D.

313-916-1088

jcarren1@hfhs.org

Locations

United States, Michigan
Henry Ford Hospital	Recruiting
Detroit, Michigan, United States, 48208
Principal Investigator: Jose Vazquez, M.D.
Sub-Investigator: Joseph Carreno, Pharm.D.
Sub-Investigator: Susan Davis, Pharm.D.
Sub-Investigator: Rachel Chambers, Pharm.D.

Sponsors and Collaborators

Henry Ford Health System

Investigators

Principal Investigator:

Jose Vazquez, M.D.

Henry Ford Hospital

More Information

No publications provided

Responsible Party:	Jose Vazquez, M.D., Henry Ford Health System
ClinicalTrials.gov Identifier:	NCT01734694 History of Changes
Other Study ID Numbers:	7089
Study First Received:	November 14, 2012
Last Updated:	November 21, 2012
Health Authority:	United States: Federal Government United States: Food and Drug Administration United States: Institutional Review Board

Additional relevant MeSH terms:

Arthritis, Infectious
Arthritis
Bacteremia
Endocarditis
Osteomyelitis
Pneumonia
Joint Diseases
Musculoskeletal Diseases
Infection
Bacterial Infections
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Heart Diseases

Cardiovascular Diseases
Bone Diseases, Infectious
Bone Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Vancomycin
Daptomycin
Linezolid
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on June 17, 2013

Safety and Efficacy of Strategy to Prevent Drug-Induced Nephrotoxicity in High-Risk Patients (STOP-NT)