Ultrafiltration vs IV Diuretics for Heart Failure

(REVERSE-HF Trial)

Recruiting at 13 trial locations

Overseen By Megan Cotts

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Nuwellis, Inc.

Must be taking: Loop diuretics, SGLT2 inhibitors, MRAs

Disqualifiers: New heart failure, Acute coronary, Sepsis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

372 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare two treatments for individuals with worsening heart failure and fluid buildup. One group will use the Aquadex Smartflow® System, a device that removes excess fluid from the body, while the other will receive IV loop diuretics, a common medication for fluid reduction. The goal is to determine which method better alleviates symptoms and improves outcomes. Individuals hospitalized for acute heart failure and experiencing fluid overload might be suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for heart failure.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should be on certain medications like oral loop diuretics, SGLT2 inhibitors, or MRAs before joining, so you might need to continue those.

What prior data suggests that the Aquadex Smartflow® System is safe for heart failure patients?

Research has shown that the Aquadex Smartflow System is safe for patients. The FDA has approved it to remove excess fluid in individuals with fluid overload, a common issue in heart failure. Studies have tested it on many heart failure patients, and it has been researched more than other similar systems, confirming its safety.

IV loop diuretics, standard treatments for heart failure, have been used for many years. They help the body remove extra salt and water, and their safety is well-established.

Overall, both treatments in this trial, the Aquadex System and IV loop diuretics, have demonstrated safety for people with heart failure. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Aquadex ultrafiltration therapy for heart failure because it offers a unique approach compared to the standard use of IV loop diuretics. Unlike diuretics that remove excess fluid by increasing urine production through the kidneys, Aquadex uses a mechanical process to directly filter excess fluid from the blood, potentially providing more controlled and efficient fluid removal. This method could be especially beneficial for patients who do not respond well to diuretics, offering a new hope for managing heart failure symptoms more effectively.

What evidence suggests that this trial's treatments could be effective for heart failure?

This trial will compare Aquadex ultrafiltration therapy with IV loop diuretics for managing fluid overload in heart failure patients. Research has shown that the Aquadex Smartflow System can assist heart failure patients with excess fluid. Studies found that this system results in greater weight and fluid loss than traditional diuretics. Specifically, patients using the Aquadex system had a 53% lower chance of hospital readmission. This treatment has improved symptoms and reduced the frequency of hospital visits for heart failure patients. Overall, these findings suggest that the Aquadex Smartflow System may be a promising alternative to IV loop diuretics for managing fluid overload in heart failure. ^{1 2 4 5 6}

Who Is on the Research Team?

Sean Pinney, MD

Principal Investigator

Mount Sinai Morningside

Maria DeVita, MD, FASN

Principal Investigator

Lenox Hill Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with worsening heart failure who are hospitalized, have been on oral loop diuretics, and show signs of fluid overload like edema. It's not for those with severe diseases expected to affect survival within 90 days, conditions preventing follow-up, contraindications to blood thinners, new heart failure diagnosis, recent heart attacks or infections.

Inclusion Criteria

Provide written informed consent

I am hospitalized for worsening heart failure.

I am on prescribed medication for heart or kidney issues.

Exclusion Criteria

I cannot take blood thinners due to health reasons.

I have inflammation of the heart muscle.

I do not have an ongoing infection or sepsis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either adjustable ultrafiltration with the Aquadex System or adjustable IV loop diuretics

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aquadex Smartflow® System
• IV Loop Diuretics

Trial Overview The REVERSE-HF study compares two treatments in patients with worsening heart failure: the Aquadex Smartflow® System which removes excess fluid from the body through ultrafiltration and traditional IV loop diuretics that help eliminate fluid via urine.

How Is the Trial Designed?

Group I: Aquadex ultrafiltration therapy Experimental Treatment 1 Intervention

Group II: IV loop diuretics Active Control 1 Intervention

Aquadex Smartflow® System is already approved in United States, European Union for the following indications:

Approved in United States as Aquadex SmartFlow System for:

• Fluid overload in patients with heart failure
• Fluid overload in pediatric patients weighing 20 kg or more
• Fluid overload in critical care patients

Approved in European Union as Aquadex SmartFlow System for:

• Temporary or extended use in adult and pediatric patients weighing 20 kg or more whose fluid overload is unresponsive to medical management, including diuretics

Who Is Running the Clinical Trial?

Nuwellis, Inc.

Lead Sponsor

Trials

11

Recruited

1,200+

Published Research Related to This Trial

Endoscopic ultrasound (EUS)-guided transmural drainage using fully covered self-expanding lumen-apposing metal stents (LAMS) is now the preferred first-line treatment for pancreatic fluid collections (PFCs) due to its safety and effectiveness, showing high clinical success and lower risks of complications compared to traditional methods.

While LAMS have advantages over plastic stents, there is still limited information on the optimal timing for their removal and the potential complications associated with this process, highlighting a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lumen-apposing metal stents in management of pancreatic fluid collections: The nobody's land of removal timing. De Angelis, CG., Venezia, L., Cortegoso Valdivia, P., et al.[2020]

In a study of 36 patients with pancreatic fluid collections, both endoscopic ultrasound (EUS)-guided drainage and surgical drainage were found to be effective, with success rates of 86% and 95% respectively.

The EUS-guided approach had lower costs and shorter hospital stays, making it suitable for mild cases, but it also had higher recurrence and complication rates compared to surgery, which is recommended for more severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel and supplementary management of pancreatic fluid collections: Endoscopic ultrasound-guided drainage. Hao, SJ., Xu, WJ., Di, Y., et al.[2020]

Loop diuretics, particularly torasemide, are recommended by European guidelines for managing heart failure, as they help reduce hospitalizations and improve symptoms and exercise capacity in patients with congestion.

For the first time, torasemide is also recommended for hypertensive patients, highlighting its expanding role in managing both heart failure and high blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Torasemide in Hypertension and Heart Failure: Re-inventing Loop Diuretic Therapy? Manolis, A., Kallistratos, M., Doumas, M.[2021]

The study found that using lumen-apposing fully covered self-expanding metal stents (LAMS) for draining pancreatic fluid collections (PFCs) is highly effective, with a technical success rate of 98.7% across 80 patients, regardless of whether the procedure was done on an inpatient or outpatient basis.

Outpatient procedures had similar rates of PFC resolution (91% vs. 87% for inpatients) but required more procedures for resolution and had higher procedure-related adverse events, indicating that while outpatient LAMS placement is safe, it may involve more follow-up compared to inpatient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placement of lumen-apposing metal stents to drain pseudocysts and walled-off pancreatic necrosis can be safely performed on an outpatient basis: A multicenter study. Adler, DG., Shah, J., Nieto, J., et al.[2022]

In a study of over 66,000 heart failure patients, torsemide was associated with the lowest 6-month all-cause mortality risk (13.2%) compared to furosemide (14.5%) and bumetanide (15.6%), suggesting it may be a more effective option for managing heart failure post-hospitalization.

The study also found that torsemide had a lower risk of composite outcomes (HF readmission or all-cause mortality) at 21.4%, compared to 24.7% for furosemide and 24.9% for bumetanide, indicating that the choice of loop diuretic can significantly impact patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effect of Loop Diuretic Prescription on Mortality and Heart Failure Readmission. Virkud, AV., Chang, PP., Funk, MJ., et al.[2023]

In a review of 14 studies involving 8127 patients with chronic heart failure, torsemide was found to significantly reduce the risk of heart failure readmissions compared to furosemide, with an odds ratio of 2.16, indicating a higher likelihood of readmission for those on furosemide.

Patients taking torsemide also showed greater improvement in their New York Heart Association class, suggesting better functional status, while there was no significant difference in mortality rates between the two diuretics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Torsemide versus furosemide and intermediate-term outcomes in patients with heart failure: an updated meta-analysis. Miles, JA., Hanumanthu, BK., Patel, K., et al.[2019]

In a meta-analysis of 15 studies involving 1746 patients, fully covered self-expanding metal stents (FCSEMS) demonstrated superior clinical success compared to double pigtail plastic stents (DPPS) for EUS-guided drainage of peripancreatic fluid collections.

Lumen-apposing metal stents (LAMS) did not show significant superiority over DPPS and were associated with a higher risk of bleeding compared to FCSEMS, indicating a need for careful consideration of stent choice based on efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of stents in endoscopic ultrasonography-guided peripancreatic fluid collection drainage: A systematic review and network meta-analysis. Park, CH., Park, SW., Nam, E., et al.[2020]

In a study involving 11 advanced heart failure patients, the System 100 UF device was used for ultrafiltration, successfully removing significant amounts of fluid in 41% of treatments, with no major complications reported.

However, 45% of patients experienced worsening renal function during treatment, highlighting the need for controlled studies to better understand the safety and efficacy of ultrafiltration in high-risk heart failure populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a novel ultrafiltration device as a treatment strategy for diuretic resistant, refractory heart failure: initial clinical experience in a single center. Liang, KV., Hiniker, AR., Williams, AW., et al.[2013]

The Nagi lumen-apposing fully covered self-expandable metal stent (LAMS) demonstrated high technical success (98.5%) and clinical success (94%) in draining pancreatic fluid collections (PFCs) in a study of 67 patients.

While the procedure is generally safe, there was a 24.2% adverse event rate, primarily due to stent migration and occlusion, particularly in patients with walled-off pancreatic necrosis (WOPN).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel lumen-apposing metal stent for the drainage of pancreatic fluid collections: An Italian multicentre experience. Petrone, MC., Archibugi, L., Forti, E., et al.[2022]

The AVOID-HF trial, which included 224 hospitalized heart failure patients, suggested that adjustable ultrafiltration (AUF) may lead to a longer time to the first heart failure event compared to adjustable intravenous loop diuretics (ALD), although the results were not statistically significant (p = 0.106).

While AUF showed a trend towards fewer heart failure and cardiovascular events at 30 days, it was associated with a higher incidence of adverse effects, indicating a need for further investigation into its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure. Costanzo, MR., Negoianu, D., Jaski, BE., et al.[2017]

Citations

1. nuwellis.com nuwellis.com/our-solutions/aquadex-smartflow/

Aquadex SmartFlow System Aquadex® therapy has been shown to have no significant clinical impact on blood pressure, heart rate, or the balance of electrolytes (e.g., sodium, potassium, ...

2. nuwellis.com nuwellis.com/healthcare-professionals/clinical-evidence/heart-failure/

Ultrafiltration Data for Heart Failure Patients UF demonstrated significantly greater weight and fluid loss than diuretics · 53% reduction in risk of readmissions with UF.

3. ir.chf-solutions.com ir.chf-solutions.com/news-releases/news-release-details/acc-2021-presentation-adds-body-evidence-supporting-nuwellis

ACC 2021 Presentation Adds to Body of Evidence Supporting ... Treatment with Aquadex therapy showed significant weight decrease, clinical symptom improvement and decreased readmissions among heart failure patients.

4. ir.nuwellis.com ir.nuwellis.com/node/17271/pdf

Nuwellis Announces Data Supporting Lower Heart Failure ... The Aquadex SmartFlow system delivers clinically proven therapy ... The Aquadex FlexFlow, which was the specific. Aquadex model used in ...

5. bcbsm.com bcbsm.com/amslibs/content/dam/public/mpr/mprsearch/pdf/104489.pdf

ULTRAFILTRATION IN DECOMPENSATED HEART ... Ultrafiltration is a technique being evaluated for removal of excess fluid from patients with volume overload and heart failure.

6. ir.chf-solutions.com ir.chf-solutions.com/node/15731/pdf

CHF Solutions Announces Data Demonstrating Benefit of ... “We are pleased with the results of these two studies confirming the benefits of Aquadex therapy in the treatment of heart failure patients, as.