Alfapump Direct Sodium Removal (DSR) Feasibility Study

Heart Failure Clinical Trial

— RED DESERT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04116034
• Other study ID #: 2019-CHF-005
• Status: Completed
• Phase: N/A
• Start date: December 26, 2019
• Est. completion date: April 15, 2021

Study information

• Verified date: May 2021
• Source: Sequana Medical N.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: April 15, 2021
• Est. primary completion date: April 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardio-Renal Syndrome
• Cardiorenal Syndrome
• Congestive Heart Failure
• Heart Failure
• Sodium Disorder
• Sodium Excess
• Volume Overload

Intervention

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

Locations

Country	Name	City	State
Belgium	OLV Ziekenhuis	Aalst
Georgia	Tbilisi Heart & Vascular Clinic	Tbilisi

Sponsors (2)

Lead Sponsor	Collaborator
Sequana Medical N.V.	Yale University

Countries where clinical trial is conducted

Belgium,  Georgia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Bioimpedance	Change in bioimpedance from baseline through treatment	At baseline, day 7, 14, and 42
Other	Hemoconcentration markers	Change in hemoglobin versus hematocrit ratio from baseline through treatment	At baseline, day 7, 14, and 42
Other	N-Terminal Prohormone of Brain Natriuretic Peptide (nt-ProBNP)	Change in nt-proBNP from basline through treatment	At baseline, day 7, 14, and 42
Other	Weight	Change in Weight from baseline through treatment	At baseline, day 7, 14, and 42
Other	Glycolated Hemoglobine (HbA1c)	Changes in HBA1c from baseline through treatment	At baseline, day 7, 14, and 42
Other	Sodium balance	Daily sodium balance	Up to day 42
Other	Fluid balance	Daily fluid balance	Up to day 42
Other	6-hour diuretic response	Change in response to 6 hour diuretic challenge from baseline through treatment	At baseline, day 14, day 42
Primary	Safety in-hospital - Device related	Rate of device related serious adverse events	Through Day 14 of treatment period
Primary	Safety in-hospital - therapy related	Rate of therapy related serious adverse events	Through Day 14 of treatment period
Primary	Safety in-hospital - procedure related	Rate of procedure related serious adverse events	Through Day 14 of treatment period
Primary	Safety during treatment period - device related	Rate of device related serious adverse events	through Day 42 of treatment period
Primary	Safety during treatment period - procedure related	Rate of procedure serious adverse events	through Day 42 of treatment period
Primary	Safety during treatment period - therapy related	Rate of therapy related serious adverse events	through Day 42 of treatment period
Secondary	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
Secondary	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