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

Official title

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

Overview

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.

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.

Interventions

• 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 Standard care
  Participants will receive usual clinical management of loop diuretics at the discretion of the treating physician, without natriuresis-guided adjustment.
• 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 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.

Primary outcome measures

• Change in Clinical Congestion Score (Group 1) [Time frame: 90 Days]
• Successful Down-Titration of Loop Diuretics (Group 2) [Time frame: 90 Days]

Secondary outcome measures (12)

• Dyspnea Visual Analogue Scale (VAS) Area Under the Curve [Time frame: 90 Days]
• Change in Kansas City Cardiomyopathy Questionnaire (KCCQ-12) Score [Time frame: 90 Days]
• Change in New York Heart Association Functional (NYHA) Functional Classification [Time frame: Baseline, 30 days, 90 days]
• Signs of Volume Overload [Time frame: Proportion of participants with clinical signs of volume overload.]
• Change in Body Weight [Time frame: 90 Days]
• Loop Diuretic Use and Dose [Time frame: Baseline, 30 days, 90 days]
• Guideline-Directed Medical Therapy (GDMT) Use [Time frame: 90 days]
• NT-proBNP Concentration [Time frame: 90 days]
• Hemoconcentration [Time frame: 90 days]
• Change in Creatinine and BUN [Time frame: 90 days]
• Worsening Renal Function [Time frame: 90 days]
• Hypokalemia [Time frame: 90 Days]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 1 center

• Vancouver General Hospital — Vancouver

Identifiers

NCT: NCT07369856 · H25-01581

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗