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

Trial Summary

What is the purpose of this trial?

The REVERSE-HF study is a randomized controlled trial to evaluate clinical outcomes of adjustable ultrafiltration with the Aquadex System as compared to adjustable IV loop diuretics in patients with worsening heart failure (HF) and fluid overload.

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 data supports the effectiveness of the treatment Aquadex Smartflow® System and loop diuretics for heart failure?

Research shows that torsemide, a type of loop diuretic, may have a slightly lower risk of death and heart failure readmission compared to other diuretics like furosemide and bumetanide. Additionally, the AVOID-HF trial suggests that ultrafiltration, like that used in the Aquadex Smartflow® System, might help delay heart failure events after hospital discharge compared to intravenous diuretics. ^{1 2 3 4 5}

What makes the Aquadex Smartflow System treatment unique for heart failure?

The Aquadex Smartflow System is unique because it uses ultrafiltration, a process that removes excess fluid from the blood, which can be more precise and controlled compared to traditional IV diuretics (medications that help the body get rid of excess fluid through urine). This method can be particularly beneficial for patients who do not respond well to diuretics. ^{6 7 8 9 10}

Research Team

Sean Pinney, MD

Principal Investigator

Mount Sinai Morningside

Maria DeVita, MD, FASN

Principal Investigator

Lenox Hill Hospital

Eligibility Criteria

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 18 years old or older.

I am hospitalized for worsening heart failure.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Comparative Effect of Loop Diuretic Prescription on Mortality and Heart Failure Readmission. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure. [2017]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Torasemide in Hypertension and Heart Failure: Re-inventing Loop Diuretic Therapy? [2021]

4. United States 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. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Torsemide versus furosemide and intermediate-term outcomes in patients with heart failure: an updated meta-analysis. [2019]

6. China 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Novel lumen-apposing metal stent for the drainage of pancreatic fluid collections: An Italian multicentre experience. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Novel and supplementary management of pancreatic fluid collections: Endoscopic ultrasound-guided drainage. [2020]

9. India pubmed.ncbi.nlm.nih.gov

Lumen-apposing metal stents in management of pancreatic fluid collections: The nobody's land of removal timing. [2020]

10. Australia pubmed.ncbi.nlm.nih.gov

Comparative efficacy of stents in endoscopic ultrasonography-guided peripancreatic fluid collection drainage: A systematic review and network meta-analysis. [2020]