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

This study has been terminated.
(Independent biostatistician recommended early termination of the trial due to low probability of success.)
Sponsor:
Information provided by (Responsible Party):
Jose Vazquez, Henry Ford Health System
ClinicalTrials.gov Identifier:
NCT01734694
First received: November 14, 2012
Last updated: July 8, 2013
Last verified: July 2013
  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:


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.



Enrollment: 100
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

  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
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: NCT01734694

Locations
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48208
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: July 8, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Arthritis
Arthritis, Infectious
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 July 28, 2014