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

Phase 4

Terminated

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

Interventions: Drug: Vancomycin
Drug: Ceftaroline
Drug: Daptomycin
Drug: Linezolid

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.

Recruitment & Eligibility

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

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Proportion of Individuals With Nephrotoxicity	Day 1 and daily serum creatinine assessment up to date of discharge from hospital, and a median of 7 days.	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.

Secondary Outcome Measures

Name	Time	Method
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.	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.
Proportion of Individuals With Clinical Success	Daily assessment of signs and symptoms of infection, and a median of 7 days.	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.