Treatment for heart failure patients with fluid overload using a new infusion method

A Prospective, Randomized Study of Infusate 2.0 Direct Sodium Removal (DSR) Treatment in Subjects With Chronic Heart Failure (CHF) Induced Persistent Congestion, Resistant to Loop Diuretic Treatment.

This study is testing a new way to help heart failure patients who have trouble getting rid of extra fluid by using a special treatment called Direct Sodium Removal therapy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sequana Medical N.V. (Industry-sponsored)
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT05965934 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of Direct Sodium Removal (DSR) therapy using the Infusate 2.0 solution in patients with heart failure who are resistant to diuretics and experiencing persistent volume overload. Initially, a non-randomized cohort will receive the treatment alongside their usual care, followed by a randomized phase where participants will be assigned to either the DSR treatment or optimized usual care. The treatment involves the implantation of a peritoneal dialysis catheter to administer the infusate, which will be adjusted based on individual response and tolerability over a four-week period. After treatment, participants will be monitored for safety for an additional three months.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with symptomatic heart failure, persistent volume overload, and a history of diuretic resistance.

Not a fit: Patients who do not have heart failure or those with severe renal impairment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve fluid management in heart failure patients who do not respond to standard diuretics.

How similar studies have performed: While similar approaches have been explored, this specific method of DSR therapy using Infusate 2.0 is novel and has not been extensively tested in prior studies.

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

Where this trial is running

New Haven, Connecticut

• Yale University — New Haven, Connecticut, United States (Recruiting)

Study contacts

• Principal investigator: Jeffrey Turner, MD — Yale Universtiry
• Study coordinator: Jeroen Capel

Conditions Heart Failure; Volume Overload; Direct Sodium Removal