MOJAVE: Management of Volume Overload HF Patients by Individual DSR Treatment adJustment-a clinicAl inVestigation of InfusatE2.0
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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.
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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.
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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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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). |
Drug: Direct 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.
Other Names:
|
| No Intervention: 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). Participants then enter enter a 3 month safety follow-up period (D29-D120) until the end of study (D120). |
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Change in Urine sodium output from baseline to end of treatment period [from Day 1 to day 28 (treatment period)]
Efficacy
Eligibility Criteria
Criteria
Inclusion Criteria:
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Aged ≥18 years at screening
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Weight at screening ≥50 kg (110 lbs)
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Creatinine-based estimated glomerular filtration rate (eGFR) (CKD-EPI] 2021 formula) ≥30 mL/min/1.73m² at screening
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6-hour cumulative urine sodium excretion <100 mmol to 40 mg IV furosemide on diuretic challenge
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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
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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
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Systolic blood pressure ≥90 mmHg and <180 mmHg
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Receiving maximally tolerated stable doses of guideline-directed medical therapy (GDMT)
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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
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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:
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Reversible cause of persistent decompensation or diuretic resistance
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Contraindications for peritoneal dialysis (PD) or PD catheter placement
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Known contraindication to icodextrin use
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Known contraindication or intolerance or allergy to SGLT2 inhibitors
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Current diagnosis of severe bladder dysfunction
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Imminent need for hospitalization
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Current or prior (past 6 months) use of renal replacement therapy
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Anemia with hemoglobin <8 g/dL
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Serum sodium <130 mEq/L
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Severe albuminuria (urinary albumin/creatinine ratio >1 at screening)
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Severe cardiac cachexia
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Clinically significant cirrhosis or history of clinically significant ascites (i.e., prior large volume paracentesis) or large volume ascites on imaging or exam
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Type 1 diabetes, uncontrolled Type 2 diabetes, "brittle" diabetes or frequent hypoglycemia or severe hyperglycemic episodes requiring emergent intervention in the last 6 months
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Known or suspected low output HF
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Prior or planned heart transplant or mechanical cardiac support implantation (LVAD)
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History of severe hyperkalemia > 5.5 mEq/L (past 6 months) or screening plasma potassium >4.5 mEq/L
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Significant non-cardiac disease or comorbidities expected to reduce life expectancy to <1 year or to interfere with safety or conduct of the study
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Severe restrictive or obstructive HF or hemodynamically significant, severe uncorrected stenotic valvular disease
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Receiving anticoagulation or antiplatelet treatment, which cannot be withheld (bridging therapy allowed)
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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)
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Received treatment with other investigational products or devices within 30 days of screening or 5 halflives of the previous investigational product
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Pregnancy or lactation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Yale University | New Haven | Connecticut | United States | 06510 |
Sponsors and Collaborators
- Sequana Medical N.V.
Investigators
- Principal Investigator: Jeffrey Turner, MD, Yale Universtiry
- Principal Investigator: Marath Fudim, MD MHS, Duke University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2022-CHF-012