The Selective Cytopheretic Device (SCD) for Acute Kidney Injury (AKI) and Hepatorenal Syndrome (HRS) Type I

Study Overview
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Brief Summary
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This research study is being done to learn what effect 7 days of treatment with the Selective Cytopheretic Device (SCD) will have on these white blood cells in the bloodstream of patients with hepatorenal syndrome and to learn whether it has any effect on the blood circulation and kidney function.

Official Title
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Investigator Initiated Pilot Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device (SCD) to Treat ICU Patients With Acute Kidney Injury (AKI) and Hepatorenal Syndrome (HRS) Type I

Conditions
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Acute Kidney Injury, Hepatorenal Syndrome

Intervention / Treatment
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* Device: Selective Cytopheretic Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cirrhosis with ascites. Not currently listed for liver transplant. Worsening renal failure most likely due to Hepatorenal Syndrome Type I with low glomerular filtration rate (GFR). No sustained improvement in renal function after diuretic withdrawal and expansion of plasma volume with 1.5 liters of plasma expander. No sustained improvement in renal function or intolerant to treatment with octreotide and /or midodrine. Able to tolerate regional citrate anticoagulation and continuous renal replacement therapy (CRRT) for 24 hours or greater. Intent to deliver full supportive care through aggressive management utilizing all available therapies for a minimum of 96 hours. Receiving medical care in an intensive care unit. Absence of shock, ongoing bacterial infection and fluid losses, and current treatment with nephrotoxic medications, hepatocellular carcinoma. Females of child bearing potential who are not pregnant (confirmed by a negative serum pregnancy test) and not lactating if recently post-partum. Two (2) consecutive intra-circuit Ionized Calcium (iCa) levels <0.40 Millimoles per liter (mmol/L), at least 30 minutes apart. Exclusion Criteria: Evidence of chronic kidney disease Stage 4. Patients with Model for End-Stage Liver Disease (MELD) score > 40 (since these patients are unlikely to survive a 90-day follow-up period). Acute or chronic use of circulatory support device. Mechanical ventilation for greater than 7 consecutive days. AKI occurring in the setting of burns, obstructive uropathy, allergic interstitial nephritis, acute or rapidly progressive glomerulonephritis, vasculitis, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP), malignant hypertension, scleroderma renal crisis, atheroembolism, functional or surgical nephrectomy, cyclosporine or tacrolimus nephrotoxicity. No evidence of intrinsic parenchymal renal disorder, ultrasonic evidence of obstructive uropathy or proteinuria greater than 500 mg/day. Presence of any organ transplant at any time. Metastatic malignancy which is actively being treated or may be treated by chemotherapy or radiation during the subsequent three-month period after study protocol therapy. Severe, uncontrolled cardiac disease. Chronic immunosuppression. Medical history of HIV or AIDS. 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 is moribund or chronically debilitated for whom full supportive care is not indicated. Dry weight >150 kg. Platelet count <30,000/mm3. Concurrent enrollment in another interventional clinical trial. Patients enrolled in clinical studies where only measurements and/or samples are taken (i.e., no test device or test drug used) are allowed to participate Use of any other investigational drug or device within the previous 30 days Patient is a prisoner.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Experimental: Selective Cytopheretic Device<br>Subjects will be placed on Selective Cytopheretic Device (SCD) for planned daily 24 hour therapy for up to 7 consecutive days. | Device: Selective Cytopheretic Device<br>* The Selective Cytopheretic Device (SCD) treatment will be delivered using a two-cartridge system using a type of dialysis equipment commonly used for conventional hemodialysis therapy. The SCD cartridge will be added immediately post-hemofilter to the circuit of a standard hemodialysis system, and treatment will be delivered for 24 hours. Blood exchange will occur using a dialysis catheter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of serious adverse events related to selective cytopheretic device (SCD) |  | Up to 90 days | 
| Number of deaths related to selective cytopheretic device |  | Up to 90 days | 
| Number of events of significant clotting within the device as assessed by visual inspection | Source documentation will record either present, absent, or not-assessed | Up to 7 days | 
| Number of unforeseen malfunction(s) that results in the need for discontinuation |  | Up to 7 days | 
| Number if events with evidence of leakage (i.e., cracking/breakage of a port, connector, SCD casing cartridge or tubing). |  | Up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dialysis independence | Dialysis independence at days 1-5 post SCD, and at days 30 and 90 (+/- 7 days). Dialysis independence will be assessed using the medical record. | Up to 90 (+/- 7 days) | 
| Change in renal function | As measured by serum creatinine from baseline (prior to dialysis initiation) at days 1-5 post SCD and at days 30 and 90 (among survivors and those free from dialysis). | Baseline (prior to dialysis), days 1-5 post SCD, days 30 and 90 (among survivors and those free from dialysis) (+/- 7 days) | 
| Change in liver function | Measured by blood tests of liver function parameters such as AST, ALT, alkaline phosphatase | Baseline, at days 1-5 post SCD or until ICU discharge (if earlier than 5 days) and at days 30 and 90 (among survivors) | 
| Change in liver function | Measured by blood test of bilirubin | Baseline (prior to dialysis), Days 1-5 post SCD or until ICU discharge (if earlier than 5 days) and at days 30 and 90 (among survivors) (+/- 7 days). | 
| Change in coagulation parameters | Coagulation parameters include Prothrombin Time (PT), Activated Partial Thromboplastin Time (PTT), and International Normalized Ratio (INR) all reported in seconds | Baseline (prior to dialysis), Days 1-5 post SCD or until ICU discharge (if earlier than 5 days) and at days 30 and 90 (among survivors) (+/- 7 days). | 
| Change in model for end-stage liver disease (MELD) score | MELD score is a number that ranges from 6 (least sick) to 40 (most sick) based on blood tests which ranks the degree of sickness from liver disease. | Baseline (prior to dialysis), Days 1-5 post SCD or until ICU discharge (if earlier than 5 days) and at days 30 and 90 (among survivors) (+/- 7 days). |