Alfapump Direct Sodium Removal (DSR) Feasibility Study

NCT ID: NCT04116034

Last Updated: 2021-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-26
• Study Completion Date: 2021-04-15

Brief 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.

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.

Conditions

Heart Failure; Congestive Heart Failure; Cardiorenal Syndrome; Volume Overload; Sodium Excess; Sodium Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DEVICE_FEASIBILITY
• Blinding Strategy: NONE

Study Groups

DSR

Up to 10 subjects will be treated with alfapump DSR system for a total treatment period of 59 days post-implantation

Group Type: EXPERIMENTAL

alfapump DSR system

Intervention Type: DEVICE

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

Interventions

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

Intervention Type: DEVICE

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: collaborator

Sequana Medical N.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jozef Bartunek, MD

Role: PRINCIPAL_INVESTIGATOR

Onze Lieve Vrouw Hospital Aalst, Belgium

Locations

OLV Ziekenhuis

Aalst, , Belgium

Tbilisi Heart & Vascular Clinic

Tbilisi, , Georgia

Countries

Belgium; Georgia

References

Rao VS, Ivey-Miranda JB, Cox ZL, Moreno-Villagomez J, Ramos-Mastache D, Neville D, Balkcom N, Asher JL, Bellumkonda L, Bigvava T, Shaburishvili T, Bartunek J, Wilson FP, Finkelstein F, Maulion C, Turner JM, Testani JM. Serial direct sodium removal in patients with heart failure and diuretic resistance. Eur J Heart Fail. 2024 May;26(5):1215-1230. doi: 10.1002/ejhf.3196. Epub 2024 Mar 31.

Reference Type: DERIVED

PMID: 38556717 (View on PubMed)

Other Identifiers

2019-CHF-005

Identifier Type: -

Identifier Source: org_study_id