Spot Analysis of Natriuresis to Guide up- or Down-titration of Diuretic Therapy in Ambulatory Patients With Chronic Heart Failure (SAND-HF)

Spot Analysis of Natriuresis to Guide up- or Down-titration of Diuretic Therapy in Ambulatory Patients With Chronic Heart Failure (SAND-HF)

Heart failure is a chronic condition that causes congestion and frequent hospitalizations. Diuretic doses are usually adjusted based on clinical judgment without an objective measure of response. This study will test the feasibility of using point-of-care urine sodium measurements to guide up-titration or down-titration of loop diuretics in ambulatory patients with heart failure.

Participants will be assigned to one of three groups based on congestion status. Groups 1 and 2 will be randomized 1:1 to natriuresis-guided therapy or standard care. Group 3 will be observational. The 90-day pilot trial will evaluate feasibility, clinical outcomes, and usability of a urine sodium-guided titration strategy.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Diuretics
• Intervention / Treatment: Behavioral: Natriuresis-Guided Up-Titration; Other: Standard care; Behavioral: Natriuresis-Guided Down-Titration; Other: Observational Follow-up

Detailed Description

Heart failure is commonly associated with sodium retention and congestion. Loop diuretics are used to relieve congestion but are typically adjusted based on symptoms and clinical judgment. Spot urine sodium concentration is an objective measure of diuretic response that may help personalize treatment. A point-of-care urine sodium sensor provides rapid results and may support effective decongestion or safe reduction of diuretics when appropriate.

This prospective, two-center pilot study includes three clinical groups:

Group 1: Up-titration cohort Patients with clinical congestion or objective evidence of congestion. These participants will be randomized 1:1 to natriuresis-guided up-titration or standard care.

Group 2: Down-titration cohort Stable, euvolemic patients who may safely reduce diuretic therapy. These participants will be randomized 1:1 to natriuresis-guided down-titration or standard care.

Group 3: Observational cohort The first 100 screened patients who do not meet criteria for Groups 1 or 2. These participants will undergo baseline assessments and routine follow-up without intervention.

Urine sodium will be measured at baseline and follow-up visits. Randomized participants will have diuretic doses adjusted based on predefined algorithms. Standard care participants will receive usual clinical management.

The primary aim is to assess feasibility, including recruitment, retention, adherence to sampling procedures, and workflow implementation. Secondary analyses will describe clinical, laboratory, and symptom-based outcomes to inform development of a larger definitive trial.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Natalie Bloch, MD; Phone Number: 66065 604-875-4111; Email: natalie.blochisenberg@vch.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Recruiting
      • Vancouver General Hospital
      • Principal Investigator: Nathaniel Hawkins, MD
      • Contact: Amitai Segev, MD; Phone Number: 66065 604-875-4111; Email: asegev@yahoo.com
      • Sub-Investigator: Amitai Segev, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Diagnosis of heart failure according to the Universal Definition
• Use of loop diuretics
• Residing in VCH or PHC regions

Group-specific inclusion:

Group 1: Congestion score ≥5 OR objective congestion; stable furosemide ≥1 week Group 2: NYHA I-II; congestion score <5; no recent HF hospitalization; stable furosemide ≥1 month Group 3: First 100 eligible patients not meeting criteria for Groups 1 or 2

Exclusion Criteria:

• eGFR <20 mL/min/1.73m²
• Renal replacement therapy
• High-risk clinical status requiring hospitalization
• Inability to consent or perform required urine sampling

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 - Natriuresis-Guided Up-Titration; Loop diuretic doses will be up-titrated based on post-diuretic urine sodium concentration measured using a point-of-care sensor. Insufficient natriuresis (<80 mmol/L) will prompt dose escalation according to a predefined algorithm.	Behavioral: Natriuresis-Guided Up-Titration; Diuretic dose and regimen will be increased based on post-diuretic urine sodium concentration measured by a point-of-care sensor. Insufficient natriuresis (<80 mmol/L) will prompt dose escalation using a predefined algorithm.
Other: Group 1 Standard of Care (Up-Titration Control); Participants will receive usual clinical management of diuretics at the discretion of their treating physician without access to urine sodium-guided titration.	Other: Standard care; Participants will receive usual clinical management of loop diuretics at the discretion of the treating physician, without natriuresis-guided adjustment.
Experimental: Group 2 Natriuresis-Guided Down-Titration; Loop diuretic doses will be reduced based on urine sodium levels. If urine sodium ≥80 mmol/L, the current dose will be maintained; if <80 mmol/L, dose will be reduced according to a predefined algorithm. Re-titration criteria include symptomatic weight gain >2 kg in one week.	Behavioral: Natriuresis-Guided Down-Titration; Loop diuretic doses will be reduced based on urine sodium levels. If urine sodium ≥80 mmol/L, the current dose will be maintained; if <80 mmol/L, dose will be reduced according to a predefined algorithm. Re-titration criteria include symptomatic weight gain >2 kg in one week.
Other: Group 2 Standard Care (Down-Titration Control); Participants will receive usual care without urine sodium-guided adjustments.	Other: Standard care; Participants will receive usual clinical management of loop diuretics at the discretion of the treating physician, without natriuresis-guided adjustment.
Other: Group 3 Observational Cohort; Participants who do not meet inclusion criteria for Groups 1 or 2 will undergo baseline urine sodium assessment and routine clinical follow-up. No study-directed titration will occur.	Other: Observational Follow-up; Participants who do not meet inclusion criteria for Groups 1 or 2 will undergo baseline urine sodium assessment and routine clinical follow-up. No study-directed titration will occur.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful Down-Titration of Loop Diuretics (Group 2)	Proportion of Group 2 participants who maintain a reduced loop diuretic dose without needing up-titration during follow-up.	90 Days
Change in Clinical Congestion Score (Group 1)	Change in clinical congestion score among Group 1 participants. Minimum Value: 1 Maximum Value: 22 A higher score indicates a worse outcome.	90 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dyspnea Visual Analogue Scale (VAS) Area Under the Curve	Change in dyspnea over time measured using serial VAS assessments.	90 Days
Signs of Volume Overload	90 Days	Proportion of participants with clinical signs of volume overload.
Change in Body Weight	Change in Body weight	90 Days
Loop Diuretic Use and Dose	Loop Diuretic Use and Dose at different timepoints	Baseline, 30 days, 90 days
Guideline-Directed Medical Therapy (GDMT) Use	Guideline-Directed Medical Therapy (GDMT) Use	90 days
NT-proBNP Concentration	NT-proBNP Concentration changes	90 days
Hemoconcentration	Changes in hemoglobin and hematocrit.	90 days
Change in Creatinine and BUN	Change in Creatinine and BUN	90 days
Worsening Renal Function	Creatinine increase ≥100% from baseline.	90 days
Hypokalemia	Frequency of potassium <3.5 mEq/L.	90 Days
Urine Sodium ≥80 mmol/L (Group 1)	Proportion of follow-up urine samples ≥80 mmol/L.	90 Days
Point-of-Care vs Laboratory Sodium Measurement Agreement	Correlation between point-of-care and laboratory urine sodium measurements.	Baseline to 90 days
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ-12) Score	Change in heart-failure related quality of life using the KCCQ-12. 12-item version. Minimum Value: 0 Maximum Value: 100 Outcome Meaning: A higher score indicates a better outcome.	90 Days
Change in New York Heart Association Functional (NYHA) Functional Classification	Change in New York Heart Association functional classification. Minimum Value: 1 Maximum Value: 4 Outcome Meaning: A higher class indicates a worse outcome.	Baseline, 30 days, 90 days
System Usability Scale	Usability of the natriuresis-guided process. Minimum Value: 0 Maximum Value: 100 Outcome Meaning: A higher score indicates a better outcome.	90 Days

Collaborators and Investigators

• Sponsor: Cardiology Research UBC

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: January 18, 2026
• First Submitted That Met QC Criteria: January 18, 2026
• First Posted (Actual): January 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: heart failure; diuretics; management
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: H25-01581

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pilot feasibility study; data not intended for reuse.

Drug and device information, study documents

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