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

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.

Study Overview

• Status: Terminated
• Conditions: Bacteremia; Endocarditis; Acute Bacterial Skin and Skin Structure Infections; Health Care Associated Pneumonia; Osteomyelitis/Septic Arthritis
• Intervention / Treatment: Drug: Vancomycin; Drug: Ceftaroline; Drug: Daptomycin; Drug: Linezolid

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48208
      • Henry Ford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: Cubicin; Drug: Linezolid; 600 mg IV/PO q12h; Other Names: Zyvox
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;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Individuals With Acute Kidney Injury Network Modified Definition of Nephrotoxicity	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) while on the study drug. 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.	Day 1 and daily serum creatinine assessment up to date of discharge, and a median of 7 days.
Proportion of Individuals With Clinical Success	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) while on the study drug. 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.	Daily assessment of signs and symptoms of infection, and a median of 7 days.

Collaborators and Investigators

• Sponsor: Henry Ford Health System

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2011
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: November 14, 2012
• First Submitted That Met QC Criteria: November 21, 2012
• First Posted (Estimate): November 28, 2012

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Joint Diseases; Musculoskeletal Diseases; Arthritis; Bacterial Infections; Bacterial Infections and Mycoses; Cross Infection; Iatrogenic Disease; Sepsis; Bone Diseases; Bone Diseases, Infectious; Healthcare-Associated Pneumonia; Bacteremia; Arthritis, Infectious; Endocarditis; Osteomyelitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Vancomycin; Linezolid; Daptomycin; Ceftaroline fosamil
• Other Study ID Numbers: 7089