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.
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 33
- Locations
- 1
- Primary Endpoint
- Serious adverse event rate through end of treatment period
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
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).
Intervention: Direct Sodium Removal Infusate 2.0 (Drug)
Outcomes
Primary Outcomes
Serious adverse event rate through end of treatment period
Time Frame: from Day 1 to day 28 (treatment period)
Safety
Adverse event rate through end of treatment period
Time Frame: from Day 1 to day 28 (treatment period)
Safety
Secondary Outcomes
- Change in Urine sodium output from baseline to end of treatment period(from Day 1 to day 28 (treatment period))