Acute Kidney Injury in Pediatric Patients
Conditions
Keywords
Acute Kidney Injury, Continuous Renal Replacement Therapy, Blood Urea Nitrogen (BUN), Prismaflex, Pediatric
Brief summary
The primary objective of this study is to evaluate the efficacy of the Gambro Prismaflex® HF20 Set based on testing the hypothesis that it delivers sufficient renal replacement therapy to effectively treat acute kidney injury (AKI) in pediatric patients by reducing blood urea nitrogen (BUN).
Interventions
DEVICEPrismaflex HF20 CRRT Filter
DEVICEPrismaflex® System 7.10 and 7.20
Sponsors
Baxter Healthcare Corporation
Vantive Health LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Patients with a hospital admission body weight ≥8 and \<20 kg (ie, ≥17.6 and \<44.09 lbs). 2. Patients with AKI defined as either 1) AKI by the Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury Guideline serum creatinine criteria, which is a \>50% rise in serum creatinine over baseline or a 0.3 mg/dL SCr rise in 48 hours OR 2) as AKI by the Pediatric modified Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE) criteria which is a 25% reduction in estimated creatinine clearance,16 OR 3) a serum creatinine \>1.2 mg/dL. OR Patients with severe fluid overload, defined as a \>10% fluid accumulation relative to the ICU admission. 3. Patients who have received RRT previously can be included in the study if \>24 hours have elapsed since their previous RRT treatment. 4. Provide written informed consent from one or both parents, as required by the local IRB or legal guardians, unless one parent is deceased, unknown, incompetent or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child per 21 CFR Part 50.55(e).
Exclusion criteria
1. Patients a) weighing 8.0-20.0 kg with a hemoglobin of \<7.0 g/dL, b) weighing 8.0-12.0 kg with a hemoglobin of \<8.0 g/dL (unless blood prime used), and c) weighing 12.1-20.0 kg with a hemoglobin of \<7.5 g/dL (unless blood prime used). 2. Children who are wards of the state.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in BUN (mg/dL) at 24 Hours Following Initiation of CRRT | 24 hours from CRRT initiation | Blood Urea Nitrogen (BUN) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Creatinine (Umol/L) at 24 Hours Following Initiation of CRRT | 24 hours from CRRT initiation | — |
| Percent Change From Baseline in Bicarbonate (mmol/L) at 24 Hours Following Initiation of CRRT | 24 hours from CRRT initiation | — |
| HF20 Set Filter Survival Time | Up to 72 Hours after Initiation | Filters that were replaced any time CRRT was stopped for reasons other than the failure to mediate the two alarms specified were censored at their current duration of usage (filter clotted and TMP excessive). Only filters that were replaced due to the two alarms were considered events for this survival analysis. A total of 34 filters were used in the study and 22 filters were censored, leaving data from only 12 filters to complete the survival estimate. Due to the small amount of filter data available, only the 25th percentile survival estimate was used since the 50th and 75th percentiles were not reached. Filter life of filters were analyzed using a Kaplan Meier survival curve with quartile survival times after the start of CRRT. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing at Least One Prismaflex Alarms Related to Fluid Balance and Extracorpeal Life | Up to 72 hours from CRRT initiation | The end of the extracorporeal circuit life will be defined by the occurrence of one or both of the following Prismaflex ® System alarms, after which CRRT will be terminated and the extracorporeal circuit replaced: * Warning: Filter is Clotted, and/or * Caution: TMP (Trans Membrane Pressure) Excessive Alarms from Prismaflex ® System 7.10 related to fluid balance will be noted and recorded for the following alarms: * Caution: Flow Problem * Caution: Gain Limit Reached * Caution: Loss Limit Reached |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prismaflex HF20 CRRT Patients included in this arm will be treated for a minimum period of 24 hours and up to 72 hours with each Prismaflex® HF 20 Set being measured for statistical analysis at 12 hour intervals during CRRT treatment. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
| Overall Study | Two filter changes required within the first 24 hours. | 4 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Prismaflex HF20 CRRT |
|---|---|
| Age, Continuous | 40.6 months STANDARD_DEVIATION 21.47 |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 16 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 23 |
| other Total, other adverse events | 16 / 23 |
| serious Total, serious adverse events | 5 / 23 |
Outcome results
Primary
Percent Change From Baseline in BUN (mg/dL) at 24 Hours Following Initiation of CRRT
Blood Urea Nitrogen (BUN)
Time frame: 24 hours from CRRT initiation
Population: The full analysis set (FAS) was based on the intent-to-treat (ITT) principle and includes any patient who received CRRT on the Prismaflex HF20 Set for any period of time. Number of subjects (n=17) with evaluable data is shown, which is a subset of FAS (N=23).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prismaflex HF20 CRRT | Percent Change From Baseline in BUN (mg/dL) at 24 Hours Following Initiation of CRRT | -58.118 Percent Change | Standard Deviation 20.0848 |
Comparison: P Value is from a one sample t-test compared against the null hypothesis value. No adjustments were made for multiple comparisons/multiplicity in this study, since there was only one primary endpoint, one arm, and one pre-specified primary null hypothesis.p-value: 0.0008t-test, 1 sided
Secondary
HF20 Set Filter Survival Time
Filters that were replaced any time CRRT was stopped for reasons other than the failure to mediate the two alarms specified were censored at their current duration of usage (filter clotted and TMP excessive). Only filters that were replaced due to the two alarms were considered events for this survival analysis. A total of 34 filters were used in the study and 22 filters were censored, leaving data from only 12 filters to complete the survival estimate. Due to the small amount of filter data available, only the 25th percentile survival estimate was used since the 50th and 75th percentiles were not reached. Filter life of filters were analyzed using a Kaplan Meier survival curve with quartile survival times after the start of CRRT.
Time frame: Up to 72 Hours after Initiation
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prismaflex HF20 CRRT | HF20 Set Filter Survival Time | 25th Percentile | 11.79 hours |
| Prismaflex HF20 CRRT | HF20 Set Filter Survival Time | 50th Percentile | NA hours |
| Prismaflex HF20 CRRT | HF20 Set Filter Survival Time | 75th Percentile | NA hours |
Secondary
Percent Change From Baseline in Bicarbonate (mmol/L) at 24 Hours Following Initiation of CRRT
Time frame: 24 hours from CRRT initiation
Population: FAS. Number of subjects (n) with evaluable data is shown.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prismaflex HF20 CRRT | Percent Change From Baseline in Bicarbonate (mmol/L) at 24 Hours Following Initiation of CRRT | 38.287 Percent Change | Standard Deviation 29.6885 |
Secondary
Percent Change From Baseline in Creatinine (Umol/L) at 24 Hours Following Initiation of CRRT
Time frame: 24 hours from CRRT initiation
Population: FAS. Number of subjects (n) with evaluable data is shown.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prismaflex HF20 CRRT | Percent Change From Baseline in Creatinine (Umol/L) at 24 Hours Following Initiation of CRRT | -45.687 Percent Change | Standard Deviation 19.8848 |
Other Pre-specified
Number of Participants Experiencing at Least One Prismaflex Alarms Related to Fluid Balance and Extracorpeal Life
The end of the extracorporeal circuit life will be defined by the occurrence of one or both of the following Prismaflex ® System alarms, after which CRRT will be terminated and the extracorporeal circuit replaced: * Warning: Filter is Clotted, and/or * Caution: TMP (Trans Membrane Pressure) Excessive Alarms from Prismaflex ® System 7.10 related to fluid balance will be noted and recorded for the following alarms: * Caution: Flow Problem * Caution: Gain Limit Reached * Caution: Loss Limit Reached
Time frame: Up to 72 hours from CRRT initiation
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prismaflex HF20 CRRT | Number of Participants Experiencing at Least One Prismaflex Alarms Related to Fluid Balance and Extracorpeal Life | Alarm: Warning Filter Clotted | 7 participants |
| Prismaflex HF20 CRRT | Number of Participants Experiencing at Least One Prismaflex Alarms Related to Fluid Balance and Extracorpeal Life | Alarm: Caution TMP Excessive | 1 participants |
| Prismaflex HF20 CRRT | Number of Participants Experiencing at Least One Prismaflex Alarms Related to Fluid Balance and Extracorpeal Life | Alarm: Caution Flow Problem | 13 participants |
| Prismaflex HF20 CRRT | Number of Participants Experiencing at Least One Prismaflex Alarms Related to Fluid Balance and Extracorpeal Life | Alarm: Warning Loss Limit Reached | 0 participants |
| Prismaflex HF20 CRRT | Number of Participants Experiencing at Least One Prismaflex Alarms Related to Fluid Balance and Extracorpeal Life | Alarm: Warning Gain Limit Reached | 0 participants |