Direct Sodium Removal Treatment for Heart Failure

(MOJAVE Trial)

Overseen By Oliver Goedje

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sequana Medical N.V.

Must be taking: Diuretics

Must not be taking: SGLT2 inhibitors

Disqualifiers: Diabetes, Cirrhosis, Anemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Infusate 2.0, a direct sodium removal therapy, to determine its safety and effectiveness for people with heart failure who don't respond to usual diuretics. The goal is to assist those with persistent fluid build-up, which can cause breathing difficulties and swelling. Individuals with heart failure experiencing frequent swelling or fluid overload, despite regular diuretics, might be suitable for this trial. Participants will either receive the new treatment or continue with optimized standard care for comparison. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on stable doses of guideline-directed medical therapy (standard heart failure treatments) to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Direct Sodium Removal (DSR) therapy with Infusate 2.0 is generally safe for heart failure patients who do not respond well to diuretics, which help remove extra fluid. In earlier studies, patients handled this treatment well. These studies indicated that using Infusate 2.0 while stopping diuretics was possible and did not lead to major safety problems. Early results from other research also support that DSR therapy is safe and well-tolerated, making it a promising option for managing excess fluid in heart failure patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for heart failure, which often rely on loop diuretics to help the body remove excess fluid, the Direct Sodium Removal (DSR) Infusate 2.0 takes a novel approach by directly removing sodium through a technique similar to dialysis. This method uses a peritoneal dialysis catheter to clear sodium from the body, potentially reducing fluid overload without the reliance on diuretics. Researchers are excited about this treatment because it may offer a new way to manage heart failure symptoms more effectively and with fewer side effects than current options.

What evidence suggests that Direct Sodium Removal treatment might be effective for heart failure?

This trial will compare Direct Sodium Removal (DSR) therapy using the Infusate 2.0 solution with optimized usual care for heart failure. Research has shown that DSR may help treat heart failure in patients who do not respond to standard diuretics. Studies have found that DSR can safely remove extra sodium from the body through the abdominal lining, potentially improving heart failure symptoms. In previous patients, DSR allowed them to stop using diuretics while still managing excess fluid. This method has proven both practical and safe, which is crucial for those who struggle with regular treatments. These findings suggest that DSR could be a helpful option for managing heart failure in certain patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Marath Fudim, MD MHS

Principal Investigator

Duke University

Jeffrey Turner, MD

Principal Investigator

Yale Universtiry

Are You a Good Fit for This Trial?

Adults over 18 with heart failure and fluid overload who are resistant to diuretics, weigh at least 110 lbs, have a certain level of kidney function, and experience persistent swelling or elevated heart pressures. They must be on stable heart medications and not pregnant or planning pregnancy without using effective contraception.

Inclusion Criteria

You weigh at least 110 pounds at the screening.

Your systolic blood pressure should be between 90 and 180 mmHg.

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

I am on blood thinners that cannot be stopped for the trial.

I haven't had any major heart or stroke events in the last 3 months.

Pregnancy or lactation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observation

Participants undergo a 14-day observation period before starting treatment

2 weeks

1 visit (in-person)

Treatment

Participants receive DSR Infusate 2.0 treatment for 4 weeks, with adjustments based on treatment effect and tolerability

4 weeks

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Monthly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Infusate 2.0

Trial Overview The trial is testing the safety and effectiveness of Direct Sodium Removal (DSR) therapy using Infusate 2.0 in patients with stubborn fluid overload despite taking diuretics. Participants will either receive this new treatment or continue their usual care.

How Is the Trial Designed?

Group I: Direct Sodium Removal (DSR) Infusate 2.0 Experimental Treatment 1 Intervention

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).

Group II: Optimized Usual Care for HF Active Control 1 Intervention

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).

Infusate 2.0 is already approved in United States, European Union for the following indications:

Approved in United States as Infusate 2.0 for:

• Management of volume overload in heart failure patients with diuretic resistance

Approved in European Union as Infusate 2.0 for:

• Management of volume overload in heart failure patients with diuretic resistance

Who Is Running the Clinical Trial?

Sequana Medical N.V.

Lead Sponsor

Trials

16

Recruited

820+

Published Research Related to This Trial

The SODIUM-HF trial, involving heart failure patients, demonstrated that reducing dietary sodium intake to less than 100 mmol per day can lead to significant improvements in heart failure symptoms and overall health outcomes.

This international, open-label, randomized controlled trial provides strong evidence supporting sodium reduction as a safe and effective dietary intervention for managing heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced dietary sodium did not reduce clinical events in heart failure. Alvarado, F., Borzak, S.[2022]

In a study of 902 heart failure patients followed for a median of 36 months, sodium restriction (<2,500 mg/d) was linked to a significantly higher risk of death or hospitalization due to heart failure, with a hazard ratio of 1.85, indicating that sodium restriction may worsen outcomes for these patients.

The increased risk associated with sodium restriction was particularly notable in patients not receiving certain heart medications, suggesting that sodium intake guidelines may need to be reconsidered for specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Dietary Sodium Restriction on Heart Failure Outcomes. Doukky, R., Avery, E., Mangla, A., et al.[2018]

A pilot study involving 50 patients with heart failure with reduced ejection fraction (HFREF) found that a low sodium-potassium enriched salt substitute was safe to use compared to regular salt over a 12-week period, with no significant differences in vital signs or kidney function.

The study also showed a small but significant improvement in exercise capacity (measured by the 6-minute walk distance) in patients using the salt substitute, suggesting potential benefits that warrant further randomized clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of salt substitution with a low sodium-potassium enriched dietary salt in patients with heart failure with reduced ejection fraction: A pilot study. Bistola, V., Arfaras-Melainis, A., Trogkanis, E., et al.[2021]

In a study of 51 hospitalized patients with severe heart failure, supplying additional sodium chloride effectively corrected hyponatremia, with 98% of patients showing improved symptoms upon discharge.

The treatment was safe, as no cases of heart failure exacerbation or hypernatremia were observed, indicating that additional sodium chloride can be a beneficial intervention in managing hyponatremia in heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical experience of supplying sodium chloride for the treatment of patients with severe heart failure]. He, LX., Sun, LL., Yang, YJ., et al.[2015]

In a pilot study involving 83 heart failure patients, a 12-week trial of 1500-mg sodium meals showed improved quality of life compared to 3000-mg meals, indicating that lower sodium intake may benefit patients' well-being.

Both sodium diets effectively reduced urinary sodium levels without significant adverse effects, suggesting that further research on dietary sodium in heart failure patients is warranted, despite challenges in participant compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low- Versus Moderate-Sodium Diet in Patients With Recent Hospitalization for Heart Failure: The PROHIBIT (Prevent Adverse Outcomes in Heart Failure by Limiting Sodium) Pilot Study. Kalogeropoulos, A., Papadimitriou, L., Georgiopoulou, VV., et al.[2021]

In a study of 342 heart failure patients who received left ventricular assist devices (LVADs), serum sodium levels significantly improved after implantation, indicating a positive response to the treatment.

However, hyponatremia (low sodium levels) at 3 months post-implantation was linked to a much higher risk of all-cause mortality (3.69 times greater) and recurrent heart failure hospitalizations, suggesting it may reflect ongoing heart failure severity or neurohormonal activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyponatremia Is a Powerful Predictor of Poor Prognosis in Left Ventricular Assist Device Patients. Tibrewala, A., Wehbe, RM., Wu, T., et al.[2023]

In a study of 107 patients with refractory congestive heart failure (CHF), the combination of high-dose furosemide and hypertonic saline solution (HSS) significantly improved diuresis and serum sodium levels compared to furosemide alone, indicating enhanced efficacy in managing fluid retention.

Patients receiving the furosemide and HSS combination had a lower readmission rate and better survival outcomes over a follow-up period of approximately 31 months, with a mortality rate of 22% compared to 44% in the furosemide-only group, suggesting a potential long-term benefit of this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects. Licata, G., Di Pasquale, P., Parrinello, G., et al.[2013]

In patients with mild heart failure, there is a significant Na+ retention response to high salt intake, with a cumulative Na+ balance exceeding that of normal subjects by 110 mmol, indicating impaired renal Na+ handling.

Treatment with enalapril effectively normalizes Na+ balance and improves renal Na+ delivery mechanisms, suggesting that early intervention can reverse renal dysfunction associated with mild heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrarenal determinants of sodium retention in mild heart failure: effects of angiotensin-converting enzyme inhibition. Volpe, M., Magri, P., Rao, MA., et al.[2019]

Citations

1. sequanamedical.com sequanamedical.com/press-releases/publication-in-kidney-medicine-highlights-benefits-of-dsr-2-0-for-sequana-medicals-direct-sodium-removal-heart-failure-program-and-board-composition-update/

Publication in Kidney Medicine Highlights Benefits of DSR ... These results build on clinical proof of concept published in European Journal of Heart Failure for DSR as a potential drug therapy for diuretic ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05965934

Management of Volume Overload HF Patients by Individual ... 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 ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/ejhf.3196

Serial direct sodium removal in patients with heart failure ... In patients with HF and diuretic resistance, serial direct sodium removal (DSR) therapy with loop diuretic withdrawal was feasible and safe.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38556717/

Serial direct sodium removal in patients with heart failure ... Direct sodium removal (DSR) using the peritoneal membrane, in conjunction with complete diuretic withdrawal, may improve CRS and diuretic resistance.

5. withpower.com withpower.com/trial/phase-2-heart-failure-6-2023-addf4

Direct Sodium Removal Treatment for Heart Failure A study found that using a low sodium-potassium enriched salt substitute can be safe and potentially effective for heart failure patients, suggesting that ...

6. sequanamedical.com sequanamedical.com/press-releases/strong-data-from-dsr-proof-of-concept-studies-in-heart-failure-published-in-european-journal-of-heart-failure/

Strong data from DSR® proof-of-concept studies in heart ... Initial data from the non-randomized cohort in the US MOJAVE study support these findings and indicated that DSR is safe and well tolerated, ...