Neutrophil and Monocyte Deactivation Via the SeLective CytopheretIc Device - A Randomized Clinical Trial in Acute Kidney Injury

Study Overview
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Brief Summary
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This randomized, controlled, pivotal study is intended to determine whether up to ten sequential 24-hour treatments with the Selective Cytopheretic Device (SCD) will improve survival in patients with Acute Kidney Injury (AKI) requiring continuous kidney replacement therapy (CKRT) when compared to CKRT alone (standard of care). This study is further intended to determine whether SCD therapy will reduce the duration of maintenance dialysis secondary to AKI. This study will enroll approximately 200 subjects across 30 US sites. Participants will be patients in an intensive care unit (ICU) setting with a diagnosis of AKI requiring CKRT.

Official Title
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A Multi-Center, Randomized, Controlled, Pivotal Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device in Patients With Acute Kidney Injury Requiring Continuous Kidney Replacement Therapy

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Device: Selective Cytopheretic Device
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to an ICU requiring CKRT: Must have AKI stage 2 or greater at the time of CKRT initiation. Must have been on CKRT for at least 12 hours but no greater than 48 hours at the time of enrollment. At least 18 years of age but not older than 80 at the time of enrollment. One additional life-threatening organ dysfunction present. Acceptable vascular access for CKRT to include adequate lumen size (at least 11.5 Fr for IJ, 13.5 Fr for femoral), and length of catheters (15cm for IJ, 24cm for femoral sites). Initial (non-binding) commitment to maintaining current level of care for at least 96 hours. C-Reactive Protein >3.5 mg/dl. Exclusion Criteria: Not expected to survive next 24 hours. Anticipated transition to comfort measures or hospice in next 4 days. Terminal condition whereby the patient is not expected to survive 28 days or any condition in which therapy is regarded as futile by the PI. Malignancy which is actively being treated or may be treated by chemotherapy or radiation. Hospitalization >14 days during this hospital admission and/or prior transfer from an outside hospital at the time of screening. Active COVID-19 infection with a primary admission diagnosis of COVID-19. Acute or chronic use of ventricular assist devices. ESRD requiring chronic kidney replacement therapy. History of CKD (greater than Stage 3). AKI stage 0 or stage 1 at the time of CKRT initiation. Non-ATN AKI diagnosis. We intend on relying on local nephrology subspecialty expertise to reasonably exclude non-ATN diagnoses based on clinical suspicions combined with prespecified objective criteria. If there is a reasonable suspicion that the subject has non-ATN AKI based on this, they will be excluded from the trial. Acute coronary syndromes, acute stroke, or acute major vascular compromise requiring medical or surgical interventions within 48 hours of randomization. Active hemorrhage requiring blood transfusions at the time of screening. Acute on Chronic Liver Failure. Suspicion of hepato-renal syndrome. Presence of any solid organ transplant at any time prior to admission. Severe burns >45% total body surface area. Bone marrow transplant within the last year. Chronic immunosuppression. Individuals who have a history of primary or secondary immune disorders including, but not limited to, HIV or AIDS. Dry weight of >150kg. Platelet count <15,000/mm3. Patient is a prisoner or member of a vulnerable population. Patient is pregnant or breast feeding. Concurrent enrollment in another interventional clinical trial. Use of any other investigational drug or device within the previous 30 days. Requiring plasmapheresis for any reason during the hospitalization.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCD + CKRT Arm<br>In addition to standard of care CKRT therapy for these subjects, these subjects will have up to ten sequential 24-hour treatments with the Selective Cytopheretic Device (SCD) in-line with their existing CKRT circuit. | Device: Selective Cytopheretic Device<br>* The Selective Cytopheretic Device (SCD) is comprised of tubing, connectors, and a synthetic hollow fiber membrane cartridge. The device is connected in series to a commercially available CKRT hemofilter. Blood from the CKRT circuit is diverted after the CKRT hemofilter through to the extracapillary space (ECS) of the SCD cartridge. Blood circulates through the SCD ECS and then it is returned to the patient via the venous return line of the CKRT circuit. Regional citrate anticoagulation is used for the entire CKRT and SCD blood circuit. The SCD cartridge incorporates a synthetic hollow fiber membrane with the ability to bind activated leukocytes to its extracapillary surface; and when used in a CKRT extracorporeal circuit in the presence of regional citrate anticoagulation, the SCD modulates inflammation.<br>* Other names: SCD;|
| Other: CKRT Alone Arm (standard of care)<br>This arm will receive standard of care CKRT therapy for their condition as appropriate. | Other: Standard of Care<br>* Standard of care CKRT for the subject's condition, as appropriate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite endpoint of mortality or dialysis dependency at 90 days | The composite of death or requiring kidney replacement therapy at 90 days post randomization | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MAKE90 | Major adverse kidney events at day 90 is a composite of death, need for KRT, or persistent renal dysfunction (final serum creatinine concentration, ≥200% of the baseline value) at the 90 day follow up period | 90 days | 
| Dialysis dependence | Need for any form of kidney replacement therapy at one year | 1 year | 
| ICU free days in the first 28 days | The number of days alive and requiring ICU level of care in the 28 days after randomization for at least 24 hours | 28 days | 
| Mortality at 28 days | Death by day 28 post randomization | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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organ failure, continuous kidney replacement therapy, continuous renal replacement therapy, acute kidney injury, inflammation, dialysis, acute tubular necrosis