Management of Volume Overload HF Patients by Individual DSR Treatment adJustment-a clinicAl inVestigation of InfusatE2.0

NCT ID: NCT05965934

Last Updated: 2023-07-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-07
• Study Completion Date: 2025-06-30

Brief Summary

This study is a multi-center, prospective, randomized (2:1), open-label study to evaluate the safety and efficacy of DSR therapy using the Infusate 2.0 peritoneal solution (composed of 30% icodextrin and 10% dextrose) in diuretic resistant patients with HF and persistent volume overload.

Detailed Description

The study will start with a non-randomized cohort in which 3 eligible subjects will be treated with Infusate 2.0 on top of their usual care while all loop diuretic treatment is stopped. A Peritoneal Dialysis (PD) catheter will be implanted to administer the infusate 14 days post-PD catheter implantation. The infusate will be drained via the same route after up to 24 hr dwell time. This DSR process will be repeated up to daily over a treatment period of 4 weeks (D1-D28). The quantity of infusate and the duration of dwell time will be adjusted based on treatment effect and tolerability.

After the treatment period, the PD catheter is removed and a 3 month safety follow-up period starts to the end of study (D29-D120).

After Data and Safety Monitoring Board (DSMB) review of 30 days follow-up data (D58) of the non-randomized cohort and DSMB approval to proceed, the 2:1 randomized enrollment of up to 30 additional subjects will be opened.

• DSR Group (N = 20) Treatment: DSR Infusate 2.0 DSR is to be started 14 days post-PD catheter implantation (= D1) for a period of 4 weeks (D28) on top of optimized usual care for HF, while loop diuretic treatment is suspended.
• Control Group (N = 10) Treatment: Optimized usual care for HF IV loop diuretic treatment is to be started (or continued) after a 14 days observation period (= D1) and can be continued for up to 4 weeks (D28).

All subjects should then enter the 3 month safety follow-up period (D29-D120) until the end of study (D120).

Conditions

Heart Failure; Volume Overload

Keywords

Direct Sodium Removal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Direct Sodium Removal (DSR) Infusate 2.0

Participants will receive a peritoneal dialysis catheter implant. DSR is to be started 14 days after catheter implantation (= D1) for a period of 4 weeks (D28) on top of optimized usual care for HF, while loop diuretic treatment is suspended. Participants then enter enter a 3 month safety follow-up period (D29-D120) until the end of study (D120).

Group Type: EXPERIMENTAL

Direct Sodium Removal Infusate 2.0

Intervention Type: DRUG

Direct Sodium Removal via peritoneal ultrafiltration using Infusate 2.0 (30% icodextrin, 10% dextrose). Patients (if not yet on SGLT-2 inhibitors) will receive SGLT-2 inhibitors.

Optimized Usual Care for HF

IV loop diuretic treatment is to be started (or continued) after a 14 days observation period (= D1) and can be continued for up to 4 weeks (D28). Participants then enter enter a 3 month safety follow-up period (D29-D120) until the end of study (D120).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Direct Sodium Removal Infusate 2.0

Direct Sodium Removal via peritoneal ultrafiltration using Infusate 2.0 (30% icodextrin, 10% dextrose). Patients (if not yet on SGLT-2 inhibitors) will receive SGLT-2 inhibitors.

Intervention Type: DRUG

Other Intervention Names

SGLT-2 inhibitor (dapagliflozin)

Eligibility Criteria

Inclusion Criteria

• Aged ≥18 years at screening
• Weight at screening ≥50 kg (110 lbs)
• Creatinine-based estimated glomerular filtration rate (eGFR) (CKD-EPI] 2021 formula) ≥30 mL/min/1.73m² at screening
• 6-hour cumulative urine sodium excretion <100 mmol to 40 mg IV furosemide on diuretic challenge
• Diagnosis of symptomatic heart failure with NYHA class III or IV AND daily diuretic dose ≥80 mg furosemide (or ≥20 mg torsemide or ≥1 mg bumetanide) for ≥14 days prior to screening AND NT-proBNP >2000 pg/mL (or BNP >400 pg/mL) OR oral daily diuretic dose ≥160 mg furosemide (or ≥40 mg torsemide or ≥2 mg bumetanide) over the previous 14 days AND ≥2 HF volume overload events within the last 6 months prior to screening or 2 HF volume overload-related hospitalizations within the last 12 months prior to screening
• Persistent mild to moderate volume overload with ≥2,3 kg (5 lbs) of excess hypervolemia AND more than trace peripheral edema AND/OR jugular venous distention AND/OR elevated filling pressure on chronic remote pressure monitoring device
• Systolic blood pressure ≥90 mmHg and <180 mmHg
• Receiving maximally tolerated stable doses of guideline-directed medical therapy (GDMT)
• For participants of childbearing potential: negative pregnancy test and agreement to use highly effective contraception for ≥1 month prior to screening and until ≥3 months after last exposure to investigational medicinal product
• For participants with intimate partners of childbearing potential: agreement to use highly effective contraception for ≥1 month prior to screening and until ≥3 months after last exposure to investigational medicinal product

Exclusion Criteria

• Reversible cause of persistent decompensation or diuretic resistance
• Contraindications for peritoneal dialysis (PD) or PD catheter placement
• Known contraindication to icodextrin use
• Known contraindication or intolerance or allergy to SGLT2 inhibitors
• Current diagnosis of severe bladder dysfunction
• Imminent need for hospitalization
• Current or prior (past 6 months) use of renal replacement therapy
• Anemia with hemoglobin <8 g/dL
• Serum sodium <130 mEq/L
• Severe albuminuria (urinary albumin/creatinine ratio >1 at screening)
• Severe cardiac cachexia
• Clinically significant cirrhosis or history of clinically significant ascites (i.e., prior large volume paracentesis) or large volume ascites on imaging or exam
• Type 1 diabetes, uncontrolled Type 2 diabetes, "brittle" diabetes or frequent hypoglycemia or severe hyperglycemic episodes requiring emergent intervention in the last 6 months
• Known or suspected low output HF
• Prior or planned heart transplant or mechanical cardiac support implantation (LVAD)
• History of severe hyperkalemia > 5.5 mEq/L (past 6 months) or screening plasma potassium >4.5 mEq/L
• Significant non-cardiac disease or comorbidities expected to reduce life expectancy to <1 year or to interfere with safety or conduct of the study
• Severe restrictive or obstructive HF or hemodynamically significant, severe uncorrected stenotic valvular disease
• Receiving anticoagulation or antiplatelet treatment, which cannot be withheld (bridging therapy allowed)
• Recent myocardial infarction, cerebrovascular accident, transient ischemic attack, coronary revascularization, arrhythmia ablation, cardiac resynchronization therapy, or surgical or transcatheter valve intervention (within 90 days prior to screening)
• Received treatment with other investigational products or devices within 30 days of screening or 5 halflives of the previous investigational product
• Pregnancy or lactation

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

Sponsors

Sequana Medical N.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Turner, MD

Role: PRINCIPAL_INVESTIGATOR

Yale Universtiry

Marath Fudim, MD MHS

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Yale University

New Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jeroen Capel

Role: CONTACT

Phone: +41 444 03 55 12

Email: Jeroen.capel@sequanamedical.com

Oliver Goedje

Role: CONTACT

Phone: +32 9 292 80 65

Email: oliver.goedje@sequanamedical.com

Facility Contacts

Jeffrey Turner, MD

Role: primary

References

McIntyre CW. Update on Hemodialysis-Induced Multiorgan Ischemia: Brains and Beyond. J Am Soc Nephrol. 2024 May 1;35(5):653-664. doi: 10.1681/ASN.0000000000000299. Epub 2024 Jan 26.

Reference Type: DERIVED

PMID: 38273436 (View on PubMed)

Other Identifiers

2022-CHF-012

Identifier Type: -

Identifier Source: org_study_id