Acute Kidney Injury
Conditions
Brief summary
The SCD PED-02 trial is examining the safety and efficacy of the Selective Cytopheretic Device (SCD) in treating pediatric acute kidney injury (AKI). AKI promotes a systemic inflammatory response syndrome (SIRS) which results in systemic microvascular damage and, if severe, multi-organ dysfunction. Activated circulating leukocytes play a central role in this process. The SCD is a synthetic membrane with the ability to bind activated leukocytes and, when used in a continuous renal replacement therapy (CRRT) extracorporeal circuit in the presence of regional citrate anticoagulation, modulates inflammation. The SCD PED-02 study will test the primary hypothesis that up to ten sequential 24-hour SCD treatments in pediatric patients with AKI will be completed safely and improve survival compared to historical controls who received CRRT alone.
Detailed description
The SCD PED-02 trial is examining the safety and efficacy of the Selective Cytopheretic Device (SCD) in treating pediatric acute kidney injury (AKI). Importantly, acute kidney injury is a highly lethal condition in critically ill patients. Despite improvements in acute medical care and advances in dialysis therapies, the mortality rate during the past four decades of this condition has not improved. Critically ill patients with AKI in hospital ICU settings have mortality rates of approximately 50%, including pediatric patients. AKI promotes a systemic inflammatory response syndrome (SIRS) which results in systemic microvascular damage and, if severe, multi-organ dysfunction. Activated circulating leukocytes play a central role in this process. Leukocytes, especially neutrophils, are major contributors to the pathogenesis and progression of many inflammatory disorders, including SIRS, sepsis, ischemia reperfusion injury, and acute respiratory distress syndrome (ARDS). Many therapeutic approaches are under investigation to limit the activation and tissue accumulation of leukocytes at sites of inflammation to minimize tissue destruction and disease progression. The SCD is comprised of tubing, connectors, and a synthetic membrane cartridge. The device is connected in series to a commercially available Continuous Renal Replacement Therapy (CRRT) device. Blood from the CRRT circuit is diverted after the CRRT hemofilter through to the extra capillary space (ECS) of the SCD. Blood circulates through this space and it is returned to the patient via the venous return line of the CRRT circuit. Regional citrate anticoagulation is used for the entire CRRT and SCD blood circuits. The SCD is a synthetic membrane with the ability to bind activated leukocytes and, when used in a continuous renal replacement therapy (CRRT) extracorporeal circuit in the presence of regional citrate anticoagulation, modulates inflammation. The SCD PED-02 study will test the primary hypothesis that up to ten sequential 24-hour SCD treatments in pediatric patients with AKI will be completed safely and improve survival compared to historical controls who received CRRT alone.
Interventions
SCD in line with CRRT extracorporeal device
Sponsors
University of Michigan
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
1. The patient's parent or legal representative has provided informed consent 2. Must be receiving medical care in an intensive care unit 3. Age less than 18 years. 4. Body weight between ≥10 and ≤ 20 kilograms 5. Intent to receive full supportive care through aggressive management 6. Clinical diagnosis of AKI requiring CRRT 7. At least one non-renal organ failure OR presence of proven/suspected sepsis
Exclusion criteria
1. Threshold blood pressure of 80/40 mmHg 2. Patients with a solid organ transplant or those with a bone marrow or stem cell transplant in the previous 100 days or who have not engrafted 3. Acute or chronic use of circulatory support device, other than extracorporeal membrane oxygenation (ECMO) 4. Presence of preexisting advanced chronic renal failure on chronic renal replacement therapy or with an estimated glomerular filtration rate less than 30 mL/min/1.73m2 5. AKI occurring in the setting of burns, obstructive uropathy, scleroderma renal crisis, atheroembolism, functional or surgical nephrectomy, cyclosporine or tacrolimus nephrotoxicity 6. Metastatic malignancy which is actively being treated or may be treated by chemotherapy or radiation during the subsequent three month period after study therapy 7. Chronic immunosuppression with the exception of corticosteroids up to a dose of 10 mg of prednisone per day 8. Known positive HIV or AIDS or COVID-19 9. Current Do not Attempt Resuscitation (DNAR), Allow Natural Death (AND), or withdrawal of care status, or anticipated change in status within the next 7 days 10. Patient not expected to survive 28 days because of an irreversible medical condition 11. Any medical condition that the Investigator thinks may interfere with the study objectives 12. Treating clinician does not feel it is in the best interest of the patient 13. Platelet count \<15,000/mm3 14. Concurrent enrollment in another interventional clinical trial 15. Use of any other investigational drug or device within the previous 30 days 16. Use of AN-69 hemofilter membrane for CRRT
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of SCD-related Adverse Events (AE) | From enrollment to Day 60 post treatment | Total number of AEs across all participants that are considered to be at least possibly related to SCD therapy per the site investigator |
| Number of Unanticipated Adverse Device Effects (UADE) | From enrollment to Day 60 post treatment | Total number of UADEs across all participants treated with the SCD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | Day 28 post treatment | Mortality rate as a percent of all participants treated with the SCD |
| Renal Recovery | Day 28 post treatment | Percent of patients free from chronic dialysis treatments |
| Hospital Length of Stay | From enrollment to Day 60 post treatment | Total days each participant spends as an inpatient at an acute care facility |
| Intensive Care Unit (ICU) Length of Stay | From enrollment to Day 60 post treatment | Total days each participant spends in an ICU during the primary admission |
Countries
United States
Participant flow
Pre-assignment details
After consent was obtained, participants entered the screening period. If their clinical status changed and the investigator believed that they no longer met eligibility criteria, the participant would be recorded as a screen failure. Criteria this may impact included resuscitation status, hypotension, platelet count, medical condition that the investigator thought would interfere with study objectives. or treating physician believed it was not longer in the patient's best interest.
Participants by arm
| Arm | Count |
|---|---|
| SCD Treatment Pediatric patients receiving SCD + CRRT for up to 10 days
Selective Cytopheretic Device: SCD in line with CRRT extracorporeal device | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| SCD Treatment Period (up to 10 Days) | Death | 1 |
| Screening | Physician Decision | 1 |
Baseline characteristics
| Characteristic | SCD Treatment |
|---|---|
| Age, Continuous | 2.05 years |
| Body Weight, Continuous | 13.4 kilograms |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Pediatric Risk of Mortality II Score | 16.5 Scores on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 1 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 6 |
| other Total, other adverse events | 5 / 6 |
| serious Total, serious adverse events | 2 / 6 |
Outcome results
Primary
Number of SCD-related Adverse Events (AE)
Total number of AEs across all participants that are considered to be at least possibly related to SCD therapy per the site investigator
Time frame: From enrollment to Day 60 post treatment
Population: Participants who received treatment with the SCD
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SCD Treatment | Number of SCD-related Adverse Events (AE) | 1 Events |
Primary
Number of Unanticipated Adverse Device Effects (UADE)
Total number of UADEs across all participants treated with the SCD
Time frame: From enrollment to Day 60 post treatment
Population: Participants who received treatment with the SCD
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SCD Treatment | Number of Unanticipated Adverse Device Effects (UADE) | 0 Events |
Secondary
Hospital Length of Stay
Total days each participant spends as an inpatient at an acute care facility
Time frame: From enrollment to Day 60 post treatment
Population: Participants who received treatment with SCD, survived to hospital discharge, and were discharged prior to the last study visit (Day 60)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCD Treatment | Hospital Length of Stay | 24 Days |
Secondary
Intensive Care Unit (ICU) Length of Stay
Total days each participant spends in an ICU during the primary admission
Time frame: From enrollment to Day 60 post treatment
Population: Participants who received treatment with the SCD, survived to Day 60, and were ICU discharged by the last study visit (Day 60)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SCD Treatment | Intensive Care Unit (ICU) Length of Stay | 11.5 Days |
Secondary
Mortality
Mortality rate as a percent of all participants treated with the SCD
Time frame: Day 28 post treatment
Population: Participants who received treatment with the SCD
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SCD Treatment | Mortality | 1 Participants |
Secondary
Mortality
Mortality rate as a percent of all participants treated with the SCD
Time frame: Day 60 post treatment
Population: Participants who received treatment with the SCD
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SCD Treatment | Mortality | 1 Participants |
Secondary
Renal Recovery
Percent of patients free from chronic dialysis treatments
Time frame: Day 28 post treatment
Population: Participants who received treatment with the SCD and who survived to Day 28 post treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SCD Treatment | Renal Recovery | 5 Participants |
Secondary
Renal Recovery
Percent of patients free from chronic dialysis treatments
Time frame: Day 60 post treatment
Population: Participants who received treatment with the SCD and who survived to Day 60 post treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SCD Treatment | Renal Recovery | 5 Participants |