Heart Failure, Volume Overload
Conditions
Keywords
Direct Sodium Removal
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).
Interventions
DRUGDirect 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.
Sponsors
Sequana Medical N.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse event rate through end of treatment period | from Day 1 to day 28 (treatment period) | Safety |
| Serious adverse event rate through end of treatment period | from Day 1 to day 28 (treatment period) | Safety |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urine sodium output from baseline to end of treatment period | from Day 1 to day 28 (treatment period) | Efficacy |
Countries
United States
Contacts
Primary ContactJeroen Capel
Backup ContactOliver Goedje
Outcome results
None listed