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

NCT01734694 | Terminated Phase 4 Results

• 1 other identifier: 7089
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Health Care Associated Pneumonia; Osteomyelitis/Septic Arthritis; Endocarditis; Bacteremia; Acute Bacterial Skin and Skin Structure Infections

Outcome Measures

Primary Outcomes (1)

• Proportion of Individuals With Nephrotoxicity

  Increase in SCr of 0.5 mg/dL or 50% above baseline for at least two consecutive days while on the study drug and through discharge from hospital. This measure will be reported as proportion of patients with nephrotoxicity within each group in relation to the number of patients in each group.

  Day 1 and daily serum creatinine assessment up to date of discharge from hospital, and a median of 7 days.

Secondary Outcomes (2)

• Proportion of Individuals With Acute Kidney Injury Network Modified Definition of Nephrotoxicity

  Day 1 and daily serum creatinine assessment up to date of discharge, and a median of 7 days.

• Proportion of Individuals With Clinical Success

  Daily assessment of signs and symptoms of infection, and a median of 7 days.

Study Arms (2)

Vancomycin

ACTIVE COMPARATOR

Drug: Vancomycin

Comparator

ACTIVE COMPARATOR

Drug: Ceftaroline; Drug: Daptomycin; Drug: Linezolid

Interventions

Vancomycin DRUG

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;

Vancomycin

Ceftaroline DRUG

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;

Also known as: Teflaro

Comparator

Daptomycin DRUG

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

Also known as: Cubicin

Comparator

Linezolid DRUG

600 mg IV/PO q12h

Also known as: Zyvox

Comparator

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• Pregnancy
• End-stage renal disease
• Receipt of more than 4 grams of vancomycin prior to enrollment on current admission
• Absolute neutrophil count \< 1000/mm3

Sponsors & Collaborators

• Henry Ford Health System: lead

Study Sites (1)

Henry Ford Hospital

Detroit, Michigan, 48208, United States

Location

MeSH Terms

Conditions

Osteomyelitis; Arthritis, Infectious; Endocarditis; Bacteremia

Interventions

Vancomycin; Ceftaroline; Daptomycin; Linezolid

Condition Hierarchy (Ancestors)

Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Heart Diseases; Cardiovascular Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Acetamides; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Jose Vazquez
• Organization: Augusta University

JVAZQUEZ@augusta.edu

(706) 723-0105

Study Officials

• Jose Vazquez, M.D.

  Henry Ford Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: November 14, 2012
• First Posted: November 28, 2012
• Study Start: October 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: May 3, 2023
• Results First Posted: May 3, 2023

Record last verified: 2023-04

Locations

US (1)