Critical Illness, Drug Toxicity, Infections, Sepsis
Conditions
Brief summary
The purpose of Opt Vanc is to evaluate the feasibility of Bayesian dose adaptation, based on a previously-developed population pharmacokinetic (PK) model and a single optimally timed PK sample, to predict vancomycin area under the curve (AUC) in critically ill children.
Detailed description
Opt Vanc is an observational study of critically ill children prescribed IV vancomycin for a suspected infection at the Children's Hospital of Philadelphia. This study will evaluate how well Bayesian dose adaptation, based on a previously-developed population pharmacokinetic (PK) model for vancomycin and a single optimally timed vancomycin concentration, can predict vancomycin area under the curve (AUC) in critically ill children. Eligible subjects will be prescribed vancomycin and undergo routine therapeutic drug monitoring (TDM) per standard of care. At the time of TDM, each subject will have a vancomycin concentration obtained at the most informative sampling time to estimate AUC, as determined by the multiple-model optimal sampling function in PMetrics (population PK modeling program). Investigators will then compare the AUC determined using Bayesian estimation and the subject's optimally timed vancomycin concentration to the AUC determined using Bayesian estimation with all available concentrations (TDM samples plus the optimally timed sample). Investigators will also examine how AUC estimation compares to AUC calculated using standard-of-care methods (ie, log-linear equations). Further, Investigators will evaluate how well the population PK model, along with a subject's measured covariates and the optimally timed PK sample, can predict a subject's future vancomycin AUC.
Interventions
None listed
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Children's Hospital of Philadelphia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Administered intravenous vancomycin via intermittent infusion, * Eligible for vancomycin AUC monitoring, per the subject's clinical team, and * Parental/guardian permission (informed consent).
Exclusion criteria
* Receipt of renal replacement therapy, plasmapheresis, or extracorporeal membrane oxygenation (ECMO), or * Unable to provide urine and blood samples.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Vancomycin Area Under the Curve (AUC) From Optimally Timed Concentration | within 24-48 hours following enrollment | This 24-hour vancomycin area under the curve (AUC) will be estimated using Bayesian estimation based on the population pharmacokinetic (PK) model, a subject's measured covariates and the optimally timed vancomycin concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Vancomycin Area Under the Curve (AUC) Estimated Using All Available Vancomycin Concentrations | within 24-48 hours following enrollment | This 24-hour vancomycin area under the curve (AUC) will be estimated using Bayesian estimation based on the population pharmacokinetic (PK) model, a subject's measured covariates and all available measured vancomycin concentrations |
| 24-hour Vancomycin Area Under the Curve (AUC) Calculated Using Standard-of-care Methods | within 24-48 hours following enrollment | This 24-hour vancomycin area under the curve (AUC) will be calculated using standard clinical methods (Zaske-Sawchuk method) |
| Visit 2 Vancomycin Area Under the Curve (AUC) Using Optimally Timed Concentration | 24-72 hours after visit 1 | The predicted 24-hour vancomycin area under the curve (AUC) at visit 2 will be estimated using Bayesian estimation based on the population pharmacokinetic (PK) model, a subject's measured covariates and the optimally timed vancomycin concentration at visit 1 |
| Visit 2 Vancomycin Area Under the Curve (AUC) Using All Available Vancomycin Concentrations | 24-72 hours after visit 1 | The predicted 24-hour vancomycin area under the curve (AUC) at visit 2 will be estimated using Bayesian estimation based on the population pharmacokinetic (PK) model, a subject's measured covariates and all available vancomycin concentrations |
| Visit 2 Vancomycin Area Under the Curve (AUC) Calculated Using Standard-of-care Methods | 24-72 hours after visit 1 | This 24-hour vancomycin area under the curve (AUC) will be calculated using standard clinical methods (Zaske-Sawchuk method) based on measured concentrations at visit 2 |
Countries
United States
Participant flow
Recruitment details
Participants were recruited based on clinical receipt of IV vancomycin for a suspected infection and plans for therapeutic drug monitoring.
Pre-assignment details
Of 29 enrolled participants, 22 met inclusion criteria and had optimal sampling time determination performed.
Participants by arm
| Arm | Count |
|---|---|
| Study Cohort Recipients of vancomycin | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | vancomycin discontinued by clinical team | 2 |
| Overall Study | vancomycin levels not evaluable | 2 |
Baseline characteristics
| Characteristic | Study Cohort |
|---|---|
| Age, Categorical <=18 years | 18 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 6.1 years |
| Estimated glomerular filtration rate (GFR) | 136 mL/min/1.73m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 7 Participants |
| Weight | 20 kilograms |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
24-hour Vancomycin Area Under the Curve (AUC) From Optimally Timed Concentration
This 24-hour vancomycin area under the curve (AUC) will be estimated using Bayesian estimation based on the population pharmacokinetic (PK) model, a subject's measured covariates and the optimally timed vancomycin concentration
Time frame: within 24-48 hours following enrollment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Study Cohort | 24-hour Vancomycin Area Under the Curve (AUC) From Optimally Timed Concentration | 494 mg*hr/L |
Secondary
24-hour Vancomycin Area Under the Curve (AUC) Calculated Using Standard-of-care Methods
This 24-hour vancomycin area under the curve (AUC) will be calculated using standard clinical methods (Zaske-Sawchuk method)
Time frame: within 24-48 hours following enrollment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Study Cohort | 24-hour Vancomycin Area Under the Curve (AUC) Calculated Using Standard-of-care Methods | 526 mg*hr/L |
Secondary
24-hour Vancomycin Area Under the Curve (AUC) Estimated Using All Available Vancomycin Concentrations
This 24-hour vancomycin area under the curve (AUC) will be estimated using Bayesian estimation based on the population pharmacokinetic (PK) model, a subject's measured covariates and all available measured vancomycin concentrations
Time frame: within 24-48 hours following enrollment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Study Cohort | 24-hour Vancomycin Area Under the Curve (AUC) Estimated Using All Available Vancomycin Concentrations | 495 mg*hr/L |
Secondary
Visit 2 Vancomycin Area Under the Curve (AUC) Calculated Using Standard-of-care Methods
This 24-hour vancomycin area under the curve (AUC) will be calculated using standard clinical methods (Zaske-Sawchuk method) based on measured concentrations at visit 2
Time frame: 24-72 hours after visit 1
Population: Given the short timeframe, only 7 subjects had data available for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Study Cohort | Visit 2 Vancomycin Area Under the Curve (AUC) Calculated Using Standard-of-care Methods | 486 mg*hr/L |
Secondary
Visit 2 Vancomycin Area Under the Curve (AUC) Using All Available Vancomycin Concentrations
The predicted 24-hour vancomycin area under the curve (AUC) at visit 2 will be estimated using Bayesian estimation based on the population pharmacokinetic (PK) model, a subject's measured covariates and all available vancomycin concentrations
Time frame: 24-72 hours after visit 1
Population: Given the short timeframe, only 11 subjects had data available for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Study Cohort | Visit 2 Vancomycin Area Under the Curve (AUC) Using All Available Vancomycin Concentrations | 502 mg*hr/L |
Secondary
Visit 2 Vancomycin Area Under the Curve (AUC) Using Optimally Timed Concentration
The predicted 24-hour vancomycin area under the curve (AUC) at visit 2 will be estimated using Bayesian estimation based on the population pharmacokinetic (PK) model, a subject's measured covariates and the optimally timed vancomycin concentration at visit 1
Time frame: 24-72 hours after visit 1
Population: Given the short timeframe, only 11 subjects had data available for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Study Cohort | Visit 2 Vancomycin Area Under the Curve (AUC) Using Optimally Timed Concentration | 500 mg*hr/L |