Furoscix in Heart Failure Patients With Diuretic Resistance (RESISTANCE-HF)

Efficacy of Furoscix in Heart Failure Patients With Diuretic Resistance

This will be a randomized, open-label pilot study of 70 patients with and without diuretic resistance who were recently admitted and discharged for acute decompensated heart failure with and oral diuretic regimen testing whether Furoscix is more effective at achieving post-discharge outpatient diuresis than standard of care. Diuretic resistance will be identified using the BAN-ADHF (BUN, creAtinine, NP-levels, Age, Diabetes and DBP, HF hospitalization, and atrial Fibrillation) score which has been integrated into the electronic health record. The score is integer-based with a score of ≥ 12 indicating diuretic resistance with high likelihood of poor outcomes. The primary outcome is diuretic efficacy as measured by volume of urine produced 8 hours after treatment and urine sodium levels (assessed hourly or per urination episode within 8 hours of treatment).

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Combination product: Furoscix; Drug: Diuretic Therapy

Detailed Description

Heart failure is one of the leading causes of hospitalization in the United States, contributing to over 1 million emergency department visits and nearly 1 million hospitalizations for HF annually. The estimated mean cost for HF was $11,552 in 2014, totaling an estimated $11 billion. Thus, strategies to reduce the burden of acute care use for patients with heart failure are necessary. Acute decompensation of heart failure is characterized by volume overload and is primarily treated with intravenous diuretics. However, inefficient and ineffective diuresis both during hospitalization and in the post-discharge environment predispose patients to frequent readmission and a worse prognosis. Importantly, there is heterogeneity in patient response to intravenous diuresis, with an estimated 20-50% of patients having poor response to initial IV diuretic therapy. Patients who are resistant to intravenous diuresis have increased risk of rehospitalization and mortality. Importantly, our group recently derived an integer-based risk score (BAN-ADHF score) to predict patients with low diuretic efficiency.

The investigators will screen eligible patients in the inpatient setting and schedule a research appointment within 14 days after discharge. At the research appointment, patients will be consented and undergo stratified randomization based on BAN-ADHF score (≥ 12 vs. <=11). Within each stratum, patients will be randomized in a 1:1 ratio (intervention: control). The intervention arm (Furoscix over 5 hours at 8mg/mL) will be compared to a usual care group (home oral diuretic dose prescribed by discharge physician). Patients will be monitored for 8 hours in the Clinical Research Unit post-drug administration for clinical safety and to measure clinical response. This study will take place at the Clinical Research Unit in the Aston Building at UT Southwestern Medical Center.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• English-speaking patients discharged after ward hospitalization for acute decompensated heart failure
• Able to be screened and enrolled within 14 days of hospitalization
• Recent echocardiogram (6 months or less)
• Discharged with home diuretic regimen

Exclusion Criteria:

• Chronic kidney disease stage 5 (eGFR<20) or End Stage Kidney Disease
• Systolic blood pressure <100
• ICU hospitalization within 3 months
• Inotrope use within last 3 months
• Home inotropes
• Electrolyte abnormalities on discharge
• Inadequate data for BAN-ADHF score
• Pregnant
• Prior heart transplantation or left ventricular assist device
• Low-output heart failure
• Concurrent use of non-loop diuretic
• Advanced liver disease
• Severe malnutrition
• Skin/Soft tissue condition precluding Furoscix
• Inability to collect urine

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: <= 11 BAN-ADHF, Furoscix; Patients without diuretic resistance as determined by BAN-ADHF score <= 11 will receive Furoscix over 5 hours at 8 mg/mL.	Combination product: Furoscix; Study Drug: Furoscix®, (Furosemide Injection), 80 mg/10 mL is a proprietary furosemide formulation that is buffered to a neutral pH to enable subcutaneous administration and contained in a prefilled Crystal Zenith® (CZ) cartridge. Study Device: The Infusor is a compact, ethylene oxide (EtO) sterilized, single-use, electro-mechanical (battery powered, micro-processor controlled), on-body subcutaneous delivery system based on the SmartDose® Gen II 10 mL (West Pharmaceutical Services). The Furoscix Infusor is an investigational drug-device combination product. The Infusor is applied to the abdomen via a medical grade adhesive and delivers a subcutaneous infusion of Furoscix through a pre-programmed, biphasic delivery profile with 30 mg (3.75 mL) administered over the first hour, followed by 12.5 mg (1.56 mL) per hour for the subsequent 4 hours (Total dose is 80 mg (10 mL) over 5 hours).; Other Names: subcutaneous furosemide
Active Comparator: <= 11 BAN-ADHF, control; Patients without diuretic resistance as determined by BAN-ADHF score <= 11 will receive home dose oral diuretic	Drug: Diuretic Therapy; Patients will receive home dose oral furosemide or oral furosemide per standard of care.
Experimental: ≥ 12 BAN-ADHF, Furoscix; Patients with diuretic resistance as determined by a BAN-ADHF score ≥ 12 will receive Furoscix over 5 hours at 8 mg/mL.	Combination product: Furoscix; Study Drug: Furoscix®, (Furosemide Injection), 80 mg/10 mL is a proprietary furosemide formulation that is buffered to a neutral pH to enable subcutaneous administration and contained in a prefilled Crystal Zenith® (CZ) cartridge. Study Device: The Infusor is a compact, ethylene oxide (EtO) sterilized, single-use, electro-mechanical (battery powered, micro-processor controlled), on-body subcutaneous delivery system based on the SmartDose® Gen II 10 mL (West Pharmaceutical Services). The Furoscix Infusor is an investigational drug-device combination product. The Infusor is applied to the abdomen via a medical grade adhesive and delivers a subcutaneous infusion of Furoscix through a pre-programmed, biphasic delivery profile with 30 mg (3.75 mL) administered over the first hour, followed by 12.5 mg (1.56 mL) per hour for the subsequent 4 hours (Total dose is 80 mg (10 mL) over 5 hours).; Other Names: subcutaneous furosemide
Active Comparator: ≥ 12 BAN-ADHF, control; Patients with diuretic resistance as determined by a BAN-ADHF score ≥ 12 will receive home dose oral diuretic.	Drug: Diuretic Therapy; Patients will receive home dose oral furosemide or oral furosemide per standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-treatment Urine Output as Measured by Cumulative Urine Output Within 1 Day.	Post-treatment diuretic efficiency is measured by cumulative urine output in mL per mg of treatment, observed hourly through 8 hours following the administration of study therapy (Furoscix vs. oral furosemide).	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-treatment Peak Spot Urine Sodium Levels in 1 Day	Post-treatment peak spot urine sodium levels assessed hourly over 8 hours post-treatment.	1 day

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: scPharmaceuticals, Inc.
• Investigators: Principal Investigator: Ambarish Pandey, MD, MSCS, UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2023
• Primary Completion (Actual): April 22, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: August 31, 2022
• First Submitted That Met QC Criteria: September 2, 2022
• First Posted (Actual): September 6, 2022

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Natriuretic Agents; Sodium Potassium Chloride Symporter Inhibitors; Furosemide; Diuretics
• Other Study ID Numbers: STU-2022-0768

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No