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

NCT05965934 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 2022-CHF-012
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure; Volume Overload

Keywords

Direct Sodium Removal

Outcome Measures

Primary Outcomes (2)

• Adverse event rate through end of treatment period

  Safety

  from Day 1 to day 28 (treatment period)

• Serious adverse event rate through end of treatment period

  Safety

  from Day 1 to day 28 (treatment period)

Secondary Outcomes (1)

• Change in Urine sodium output from baseline to end of treatment period

  from Day 1 to day 28 (treatment period)

Study Arms (2)

Direct Sodium Removal (DSR) Infusate 2.0

EXPERIMENTAL

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).

Drug: Direct Sodium Removal Infusate 2.0

Optimized Usual Care for HF

NO INTERVENTION

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).

Interventions

Direct Sodium Removal Infusate 2.0 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.

Also known as: SGLT-2 inhibitor (dapagliflozin)

Direct Sodium Removal (DSR) Infusate 2.0

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Sequana Medical N.V.: lead

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 38273436 DERIVED

MeSH Terms

Conditions

Heart Failure; Edema

Interventions

Sodium-Glucose Transporter 2 Inhibitors; dapagliflozin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Study Officials

• Jeffrey Turner, MD

  Yale Universtiry

  PRINCIPAL INVESTIGATOR

• Marath Fudim, MD MHS

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeroen Capel

CONTACT

+41 444 03 55 12; Jeroen.capel@sequanamedical.com

Oliver Goedje

CONTACT

+32 9 292 80 65; oliver.goedje@sequanamedical.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2023
• First Posted: July 28, 2023
• Study Start: July 7, 2023
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: July 28, 2023

Record last verified: 2023-07

Locations

US (1)