Ultrafiltration Versus IV Diuretics in Worsening Heart Failure (REVERSE-HF)

A Randomized Controlled Study to Evaluate the Safety and Effectiveness of the Aquadex System in Patients With Heart Failure and Fluid Overload

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.

Study Overview

• Status: Terminated
• Conditions: Heart Failure; Fluid Overload; Heart Failure (for Example, Fluid Overload)
• Intervention / Treatment: Device: Aquadex Smartflow® System; Drug: IV Loop Diuretics

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85721
      • Banner Health
  • California
    • Long Beach, California, United States, 90806
      • MemorialCare, Long Beach Medical Center
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital, San Diego Cardiac Center
  • Florida
    • Clearwater, Florida, United States, 33756
      • BayCare Medical Group, Morton Plant
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health
  • New York
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital
    • New York, New York, United States, 10075
      • Northwell Health
    • New York, New York, United States, 10025
      • Mount Sinai Morningside
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Columbus, Ohio, United States, 43215
      • The Ohio State University
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Jefferson Health
  • Tennessee
    • Jackson, Tennessee, United States, 38301
      • Jackson Madison County General Hospital
  • Texas
    • Dallas, Texas, United States, 75207
      • Baylor Scott & White Research Institute
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Heart Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years or older
• Man, or non-pregnant woman
• Admitted to the hospital with a diagnosis of acute decompensated heart failure
• On regularly prescribed oral loop diuretics, Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors or a Mineralcorticoid Receptor Antagonists (MRA) prior to admission
• Fluid overload manifested by at least three clinical indications (e.g., edema, an excess of at least 10 pounds of fluid, etc.)
• Provide written informed consent

Exclusion Criteria:

• New diagnosis of heart failure
• Acute coronary syndromes
• Creatinine ≥ 3.0 mg/dl or planned renal replacement therapies at the time of enrollment
• Contraindications to systemic anticoagulation
• Severe concomitant disease expected to prolong hospitalization or cause death in less than 90 days
• Sepsis or ongoing systemic infection
• Active myocarditis
• Constrictive pericarditis or restrictive cardiomyopathy
• Severe aortic stenosis
• Any condition in the opinion of the investigator that would prevent the patient from follow-up/survival

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aquadex ultrafiltration therapy	Device: Aquadex Smartflow® System; ultrafiltration
Active Comparator: IV loop diuretics	Drug: IV Loop Diuretics; diuretics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first heart failure (HF) event	Heart Failure (HF) event defined as any HF rehospitalization or unplanned use of IV loop diuretics, vasoactive medications or Aquadex therapy in any outpatient setting.	within 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Win ratio analysis	Win ratio analysis of cardiovascular (CV) mortality, HF events and quality of life	within 30 days

Collaborators and Investigators

• Sponsor: Nuwellis, Inc.
• Investigators: Principal Investigator: Maria DeVita, MD, FASN, Lenox Hill Hospital; Principal Investigator: Sean Pinney, MD, Mount Sinai Morningside

Publications and helpful links

General Publications

• McCallum W, Sarnak MJ. Cardiorenal Syndrome in the Hospital. Clin J Am Soc Nephrol. 2023 Jul 1;18(7):933-945. doi: 10.2215/CJN.0000000000000064. Epub 2023 Jan 13.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Actual): October 6, 2025
• Study Completion (Actual): April 7, 2026

Study Registration Dates

• First Submitted: March 10, 2022
• First Submitted That Met QC Criteria: March 31, 2022
• First Posted (Actual): April 8, 2022

Study Record Updates

• Last Update Posted (Actual): June 25, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Heart failure; Fluid overload
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Heart Failure; Edema; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Diuretics; Natriuretic Agents; Pharmacologic Actions; Chemical Actions and Uses; Sodium Potassium Chloride Symporter Inhibitors
• Other Study ID Numbers: CLIN07687

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes