Trial Outcomes & Findings for Safety and Efficacy of Strategy to Prevent Drug-Induced Nephrotoxicity in High-Risk Patients (NCT NCT01734694)
NCT ID: NCT01734694
Last Updated: 2023-05-03
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
100 participants
Primary outcome timeframe
Day 1 and daily serum creatinine assessment up to date of discharge from hospital, and a median of 7 days.
Results posted on
2023-05-03
Participant Flow
Participant milestones
| Measure |
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;
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
51
|
49
|
|
Overall Study
COMPLETED
|
51
|
49
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Efficacy of Strategy to Prevent Drug-Induced Nephrotoxicity in High-Risk Patients
Baseline characteristics by cohort
| Measure |
Vancomycin
n=51 Participants
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;
|
Comparator
n=49 Participants
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
|
Total
n=100 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60 years
n=5 Participants
|
60 years
n=7 Participants
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
17 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American
|
32 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
64 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
51 participants
n=5 Participants
|
49 participants
n=7 Participants
|
100 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Vancomycin
n=51 Participants
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;
|
Comparator
n=49 Participants
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
|
|---|---|---|
|
Proportion of Individuals With Nephrotoxicity
|
5 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Vancomycin
n=51 Participants
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;
|
Comparator
n=49 Participants
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
|
|---|---|---|
|
Proportion of Individuals With Acute Kidney Injury Network Modified Definition of Nephrotoxicity
|
16 Participants
|
16 Participants
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Vancomycin
n=51 Participants
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;
|
Comparator
n=49 Participants
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
|
|---|---|---|
|
Proportion of Individuals With Clinical Success
Clinical Success
|
42 Participants
|
44 Participants
|
|
Proportion of Individuals With Clinical Success
Indeterminate
|
4 Participants
|
3 Participants
|
|
Proportion of Individuals With Clinical Success
Clinical Failure
|
5 Participants
|
2 Participants
|
Adverse Events
Vancomycin
Serious events: 16 serious events
Other events: 0 other events
Deaths: 0 deaths
Comparator
Serious events: 16 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vancomycin
n=51 participants at risk
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;
|
Comparator
n=49 participants at risk
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
|
|---|---|---|
|
Renal and urinary disorders
Nephrotoxicity
|
9.8%
5/51
|
6.1%
3/49
|
|
Renal and urinary disorders
Acute Kidney Injury
|
31.4%
16/51
|
32.7%
16/49
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place