Health Care Associated Pneumonia, Osteomyelitis/Septic Arthritis, Endocarditis, Bacteremia, Acute Bacterial Skin and Skin Structure Infections
Conditions
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.
Interventions
DRUGVancomycin
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;
DRUGCeftaroline
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;
DRUGDaptomycin
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
DRUGLinezolid
600 mg IV/PO q12h
Sponsors
Henry Ford Health System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vancomycin 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; | 51 |
| Comparator 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;
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
Linezolid: 600 mg IV/PO q12h | 49 |
| Total | 100 |
Baseline characteristics
| Characteristic | Vancomycin | Comparator | Total |
|---|---|---|---|
| Age, Continuous | 60 years | 60 years | 60 years |
| Race/Ethnicity, Customized African American | 32 Participants | 32 Participants | 64 Participants |
| Race/Ethnicity, Customized Caucasian | 17 Participants | 16 Participants | 33 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 51 participants | 49 participants | 100 participants |
| Sex: Female, Male Female | 17 Participants | 20 Participants | 37 Participants |
| Sex: Female, Male Male | 34 Participants | 29 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 51 | 0 / 49 |
| serious Total, serious adverse events | 16 / 51 | 16 / 49 |
Outcome results
Primary
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.
Time frame: Day 1 and daily serum creatinine assessment up to date of discharge from hospital, and a median of 7 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vancomycin | Proportion of Individuals With Nephrotoxicity | 5 Participants |
| Comparator | Proportion of Individuals With Nephrotoxicity | 3 Participants |
Secondary
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.
Time frame: Day 1 and daily serum creatinine assessment up to date of discharge, and a median of 7 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vancomycin | Proportion of Individuals With Acute Kidney Injury Network Modified Definition of Nephrotoxicity | 16 Participants |
| Comparator | Proportion of Individuals With Acute Kidney Injury Network Modified Definition of Nephrotoxicity | 16 Participants |
Secondary
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.
Time frame: Daily assessment of signs and symptoms of infection, and a median of 7 days.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vancomycin | Proportion of Individuals With Clinical Success | Clinical Success | 42 Participants |
| Vancomycin | Proportion of Individuals With Clinical Success | Indeterminate | 4 Participants |
| Vancomycin | Proportion of Individuals With Clinical Success | Clinical Failure | 5 Participants |
| Comparator | Proportion of Individuals With Clinical Success | Clinical Success | 44 Participants |
| Comparator | Proportion of Individuals With Clinical Success | Indeterminate | 3 Participants |
| Comparator | Proportion of Individuals With Clinical Success | Clinical Failure | 2 Participants |