A Multi-Center Study of a SCD for Immunomodulatory Dysregulation in Pediatric AKI

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Multi-Center, Pilot Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device (SCD) for the Treatment of Immunomodulatory Dysregulation Due to Pediatric Acute Kidney Injury (AKI)

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Device: Selective Cytopheretic Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient's parent or legal representative has provided informed consent Must be receiving medical care in an intensive care unit Age less than 18 years. Body weight between ≥10 and ≤ 20 kilograms Intent to receive full supportive care through aggressive management Clinical diagnosis of AKI requiring CRRT At least one non-renal organ failure OR presence of proven/suspected sepsis Exclusion Criteria: Threshold blood pressure of 80/40 mmHg 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 Acute or chronic use of circulatory support device, other than extracorporeal membrane oxygenation (ECMO) 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 AKI occurring in the setting of burns, obstructive uropathy, scleroderma renal crisis, atheroembolism, functional or surgical nephrectomy, cyclosporine or tacrolimus nephrotoxicity Metastatic malignancy which is actively being treated or may be treated by chemotherapy or radiation during the subsequent three month period after study therapy Chronic immunosuppression with the exception of corticosteroids up to a dose of 10 mg of prednisone per day Known positive HIV or AIDS or COVID-19 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 Patient not expected to survive 28 days because of an irreversible medical condition Any medical condition that the Investigator thinks may interfere with the study objectives Treating clinician does not feel it is in the best interest of the patient Platelet count <15,000/mm3 Concurrent enrollment in another interventional clinical trial Use of any other investigational drug or device within the previous 30 days Use of AN-69 hemofilter membrane for CRRT

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: SCD Treatment<br>Pediatric patients receiving SCD + CRRT for up to 10 days | Device: Selective Cytopheretic Device<br>* SCD in line with CRRT extracorporeal device<br>* Other names: SCD-F40;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | From enrollment to Day 60 post treatment | 
| Number of unanticipated adverse device effects (UADE) | Total number of UADEs across all participants treated with the SCD | From enrollment to Day 60 post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Mortality rate as a percent of all participants treated with the SCD | Day 28 and Day 60 post treatment | 
| Renal Recovery | Percent of patients free from chronic dialysis treatments | Day 28 and Day 60 post treatment | 
| Hospital Length of Stay | Total days each participant spends as an inpatient at an acute care facility | From enrollment to Day 60 post treatment | 
| Intensive Care Unit (ICU) Length of Stay | Total days each participant spends in an ICU during the primary admission | From enrollment to Day 60 post treatment |