Flexible vs. Fixed Diuretic Regimen in the Management of Chronic Heart Failure: A Pilot Study

Heart failure is a major cause of death and hospitalization in Canada. Many of the symptoms experienced by patients with heart failure relate to having fluid accumulate in the lungs causing difficulty breathing, swelling in the legs, and an increase in weight. Thus, one of the cornerstones of managing heart failure includes the use of medications known as diuretics that target the kidneys to reduce fluid accumulation via urination. Deciding on the correct dose of this medication can be quite nuanced as under-dosing can lead to accumulation of fluid, and over-dosing can dehydrate patients and potentially result in lightheadedness/fainting and damage to the kidneys. Currently, options for prescribing diuretics for heart failure include 1) giving patients a regular, fixed dose or 2) having patients monitor their daily weight as a surrogate of their fluid status and then take a dose of diuretic based on a pre-prepared scale. The rationale behind the flexible weight-based diuretic scale is that it can potentially detect early fluid accumulation and thus possibly prevent hospitalization or ED visits, and it also avoids over-dosing and potentially dehydrating patients. Currently, it is not clear whether the flexible diuretic regimen is better than the fixed-dose regimen in preventing ED visits, hospitalizations, kidney damage, or death and as such, this pilot study will directly compare the two commonly used regimens in the management of chronic heart failure patients.

Study Overview

• Status: Recruiting
• Conditions: Heart Diseases; Heart Failure
• Intervention / Treatment: Other: Ambulatory heart failure management with fixed dose furosemide; Other: Ambulatory heart failure management with Flexible Diuretic Regimen with furosemide

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Stuart Smith, MD; Phone Number: (519) 663-3428; Email: stuart.smith@lhsc.on.ca
• Study Contact Backup: Name: Andy Jiang, MD; Email: andy.jiang@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4V2
      • Recruiting
      • St. Joseph's Health Care
      • Contact: Stuart Smith, MD; Phone Number: (519) 663-3428

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Diagnosis of heart failure, either reduced (Left ventricular ejection fraction [LVEF] ≤ 40%) or preserved (LVEF > 40%) ejection fraction as measured by echocardiography performed within the last 2 months
2. Prescribed and tolerating furosemide with a minimum daily dose of 40mg oral daily
3. New York Heart Association (NYHA) Class II or higher symptoms
4. NT-proBNP cutoff of ≥ 1000 pg/mL performed within 30 days prior to randomization
5. Age > 18 years
6. English speaking
7. Access to a scale and ability to weigh themselves daily and reliable telephone access

Exclusion Criteria:

1. Myocardial infarction, coronary artery bypass graft surgery, stent insertion and/or angioplasty within 14 days
2. Pregnancy
3. Inability to follow directions and self-monitor as part of a flexible diuretic regimen as discerned by the clinician
4. Allergic reaction to loop diuretics
5. Unable to provide informed consent

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
Active Comparator: Fixed - dose diuretic; Pre-determined, fixed daily dose of diuretic (furosemide)	Other: Ambulatory heart failure management with fixed dose furosemide; Subjects will be prescribed a fixed daily dose of diuretic (furosemide) as part of the standard of care ambulatory management of chronic heart failure. Follow-up will occur at 90 days with routine bloodwork to monitor renal function.
Experimental: Flexible diuretic regimen; Variable daily dose of diuretic (furosemide) determined based on a pre-specified weight-based scale.	Other: Ambulatory heart failure management with Flexible Diuretic Regimen with furosemide; Subjects will be given a regimen that determines a variable daily dose of diuretic (furosemide) based on daily self-measured weights as part of the standard of care ambulatory management of chronic heart failure. Follow-up will occur at 90 days with routine bloodwork to monitor renal function.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality and morbidity composite outcome	Time to first event of a composite outcome including: ambulatory heart failure visit (clinic or emergency department) requiring intravenous diuretic, an increase in oral diuretic dose greater than or equal to 2.5 times their baseline dose prescribed at time of randomization, or the addition of metolazone; hospitalization for heart failure and/or acute kidney injury defined as a serum creatinine > 1.5 times from baseline at time of randomization; and all-cause death up to 90 days post-randomization	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute kidney injury	Rate of acute kidney injury defined as a serum creatinine increase of >1.5 times from baseline at 90 days from randomization	90 days
Heart Failure Hospitalizations	Total number of hospitalizations due to heart failure (first and recurrent) during the 90 days post-randomization	90 days
All-cause Hospitalizations	Total number of hospitalizations for any cause during the 90 days post-randomization	90 days

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Investigators: Principal Investigator: Stuart Smith, MD, Western University

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2023
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: October 21, 2022
• First Submitted That Met QC Criteria: October 21, 2022
• First Posted (Actual): October 26, 2022

Study Record Updates

• Last Update Posted (Actual): March 13, 2023
• Last Update Submitted That Met QC Criteria: March 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: furosemide; diuretic; flexible diuretic regimen; weight-based
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Failure; Heart Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Sodium Potassium Chloride Symporter Inhibitors; Furosemide; Diuretics
• Other Study ID Numbers: REDA ID: 12724

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
• product manufactured in and exported from the U.S.: Yes