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

• 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