Alfapump Direct Sodium Removal (DSR) Feasibility Study

Study Overview
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Brief Summary
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First in Human feasibility and sfafety study of the alfapump DSR system in the treatment of Heart failure subects resistant to diuretic therapy. Up to 10 subjects will be enrolled in up to 3 centres in Belgium and Georgia and will be iplanted with the alfapump DSR system. Subjects will undergo DSR titration during a 2 week hospitalisation period, and will continue titrated DSR therapy as outpatients for 4 more weeks.

Detailed Description
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Up to 10 subjects diagnosed with stable chronic heart failure (CHF) on high oral diuretic dose and an MDRD eGFR > 30ml/min/1.73m2 will undergo subcutaneous implantation of the alfapump DSR system (Day-13) and portacath system and participate in a 6 week interventional study. Prior to an inpatient study period, the subject will undergo a 40mg IV furosemide (or 1 mg IV bumetanide) diuretic challenge with timed biospecimen collection. On day 14 post-implant (Day 0), the subject will be admitted for a 14-day period in which diuretics will be withheld and subjects will be on a strict low-sodium (3g/day) diet with strict intake/output and all urine collected and samples saved for analysis. During the first 7 days (Day 0 - 6) subjects will be treated with 1000ml of DSR Infusate Monday, Wednesday, Friday administered to the peritoneal cavity through the subcutaneous peritoneal catheter. The infusate will remain in the peritoneal cavity for a 2 hour dwell time, then all fluid will be removed from the peritoneal cavity to the urinary bladder using the alfapump DSR system over the subsequent 8 hours. On day 7, subjects will be transitioned to a moderate to high salt diet given as the same low-sodium (3g/day) diet with supplementation with sodium chloride tablets (2g/day) (5g/day total sodium), as this will likely represent their typical home sodium intake. During this time, the optimal treatment protocol (frequency of administration and volume of DSR infusate administered) for individual subjects based on daily sodium balance, weight changes, and blood pressure will be created and tested over the next seven days in hospital (Day 7 - 13). Following the inpatient period, a second diuretic challenge will be conducted. Over the subsequent 28 days, diuretics will continue to be withheld with preferential maintenance of euvolemia through DSR and subjects will come into the clinic based on their tailored therapy schedule and undergo supervised DSR infusate administration. Addition of diuretic treatment will only be allowed if maximal DSR therapy has been instituted (DSR 7 days per week (i.e., including weekends) at 1.5L per session with dwell time of 4 hours) and/or holding diuretics until additional DSR can be utilized would represent a risk to the subject, as described in the CIP diuretic algorithm. After the completion of the study period, the alfapump DSR therapy is halted and the subject undergoes a third diuretic challenge to quantify diuretic response. At this point oral diuretic therapy will be resumed. At the end of the study the alfapump can remain implanted and set to 'dormant' state after discussion and agreement between subject and investigator, and if there are no clinical, ethical or other reasons indicating explanation of the alfapump. Alternatively, the subject may elect to enroll into a low intensity follow-on study.

Official Title
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Alfapump DSR System in the Treatment of Diuretic Resistant Heart Failure Subjects

Conditions
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Heart Failure, Congestive Heart Failure, Cardiorenal Syndrome, Volume Overload, Sodium Excess, Sodium Disorder

Intervention / Treatment
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* Device: alfapump DSR system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects > 18 years of age eGFR > 30ml/min/14.73m2 Diagnosis of heart failure with one of the following: a. nt-proBNP > 400 pg/ml (or BNP > 100 pg/mp) and oral diuretic dose ≥ 80mg furosemide (or 20mg torsemide or 1mg bumetanide) OR b. Oral diuretic dose ≥ 120mg furosemide (or 30 mg torsemide or 1.5 mg bumetanide) Stable diuretic dose for 30 days Systolic blood pressure ≥ 100 mmHg Determined by treating provider to be at optimal volume status Exclusion Criteria: Candidates for participation will be ineligible for the study if any of the following exclusion criteria apply: Proteinuria > 1g/day BMI > 40 History of abdominal surgery or peritonitis Anemia with hemoglobin < 8g/dL Serum sodium < 135 mEq/L Severe hyperkalemia or baseline plasma potassium > 4.5 mEq/L Significant other organ disease or comorbidities Hospitalization within 90 days Cirrhosis Hemodynamically significant stenotic valvular disease Active or recurrent urinary tract infection or history of renal transplant History of significant bladder dysfunction expected to interfere with ability of subject to tolerate DSR pumping into bladder Uncontrolled diabetes with frequent hyperglycemia or Type 1 diabetes Subject is currently participating in another clinical trial Subject is unable to comply with all required study follow-up procedures

Ages Eligible for Study
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Minimum Age: 18 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: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: up to 10 subjects will be enrolled to evaluate feasibility and safety of thealfapump DSR system
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DSR<br>Up to 10 subjects will be treated with alfapump DSR system for a total treatment period of 59 days post-implantation | Device: alfapump DSR system<br>* Infusion of sodium free Dextrose 10% into peritoneal cavity to remove sodium and fluid using principles of peritoneal dialysis, sodium and ultrafiltrate will be evacuated to the bladder by the alfapump<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety in-hospital - Device related | Rate of device related serious adverse events | Through Day 14 of treatment period | 
| Safety in-hospital - therapy related | Rate of therapy related serious adverse events | Through Day 14 of treatment period | 
| Safety in-hospital - procedure related | Rate of procedure related serious adverse events | Through Day 14 of treatment period | 
| Safety during treatment period - device related | Rate of device related serious adverse events | through Day 42 of treatment period | 
| Safety during treatment period - procedure related | Rate of procedure serious adverse events | through Day 42 of treatment period | 
| Safety during treatment period - therapy related | Rate of therapy related serious adverse events | through Day 42 of treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibiity endpoint sodium balance in-hospital | Number of patients with neutral sodium balance (sodium intake equal to sodium output) in the absence of diuretic therapy during hospitalization period | through Day 14 of DSR therapy | 
| Feasibility endpoint sodium balance during treatment period | Number of patients with neutral sodium balance (sodium intake equal to sodium output) in the absence of diuretic therapy in a titrated schedule during treatment period | Through Day 42 of DSR Therapy |