Alfapump Direct Sodium Removal (DSR) Feasibility Study (RED DESERT)

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Congestive Heart Failure; Sodium Excess; Sodium Disorder; Cardiorenal Syndrome; Volume Overload
• Intervention / Treatment: Device: alfapump DSR system

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • OLV Ziekenhuis
• Georgia
  • Tbilisi, Georgia
    • Tbilisi Heart & Vascular Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects > 18 years of age
2. eGFR > 30ml/min/14.73m2
3. 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)
4. Stable diuretic dose for 30 days
5. Systolic blood pressure ≥ 100 mmHg
6. 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:

1. Proteinuria > 1g/day
2. BMI > 40
3. History of abdominal surgery or peritonitis
4. Anemia with hemoglobin < 8g/dL
5. Serum sodium < 135 mEq/L
6. Severe hyperkalemia or baseline plasma potassium > 4.5 mEq/L
7. Significant other organ disease or comorbidities
8. Hospitalization within 90 days
9. Cirrhosis
10. Hemodynamically significant stenotic valvular disease
11. Active or recurrent urinary tract infection or history of renal transplant
12. History of significant bladder dysfunction expected to interfere with ability of subject to tolerate DSR pumping into bladder
13. Uncontrolled diabetes with frequent hyperglycemia or Type 1 diabetes
14. Subject is currently participating in another clinical trial
15. Subject is unable to comply with all required study follow-up procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DEVICE_FEASIBILITY
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DSR; 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; 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bioimpedance	Change in bioimpedance from baseline through treatment	At baseline, day 7, 14, and 42
Hemoconcentration markers	Change in hemoglobin versus hematocrit ratio from baseline through treatment	At baseline, day 7, 14, and 42
N-Terminal Prohormone of Brain Natriuretic Peptide (nt-ProBNP)	Change in nt-proBNP from basline through treatment	At baseline, day 7, 14, and 42
Weight	Change in Weight from baseline through treatment	At baseline, day 7, 14, and 42
Glycolated Hemoglobine (HbA1c)	Changes in HBA1c from baseline through treatment	At baseline, day 7, 14, and 42
Sodium balance	Daily sodium balance	Up to day 42
Fluid balance	Daily fluid balance	Up to day 42
6-hour diuretic response	Change in response to 6 hour diuretic challenge from baseline through treatment	At baseline, day 14, day 42

Collaborators and Investigators

• Sponsor: Sequana Medical N.V.
• Collaborators: Yale University
• Investigators: Principal Investigator: Jozef Bartunek, MD, Onze Lieve Vrouw Hospital Aalst, Belgium

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 26, 2019
• Primary Completion (ACTUAL): April 15, 2021
• Study Completion (ACTUAL): April 15, 2021

Study Registration Dates

• First Submitted: October 1, 2019
• First Submitted That Met QC Criteria: October 2, 2019
• First Posted (ACTUAL): October 4, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 28, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Heart Failure; Cardio-Renal Syndrome
• Other Study ID Numbers: 2019-CHF-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD data will be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No