SURE-HF: Urinary Sodium-Guided Diuretic Therapy in Heart Failure

Official title

Urinary Sodium-Guided Optimization of Diuretic Therapy in Patients With Worsening Heart Failure: Rationale and Design of a Pragmatic Randomized Controlled Trial (SURE-HF Trial)

Overview

The SURE-HF trial is a pragmatic, multicentre, randomized controlled study evaluating natriuresis-guided optimization of intravenous loop diuretic therapy in patients hospitalized with worsening heart failure (WHF). The study aims to determine whether serial urinary sodium assessment combined with a structured decongestive treatment algorithm improves decongestion, reduces the need for therapy escalation, and enhances discharge readiness compared with standard care. Participants will be randomized to standard urine output-guided therapy or natriuresis-guided decongestive strategies using different intravenous loop diuretic administration regimens. The study integrates bedside diagnostic tools including lung ultrasound, inferior vena cava assessment, focused echocardiography, and serial clinical congestion monitoring. The primary endpoint is a hierarchical composite outcome including escalation of heart failure therapy, persistent congestion at discharge, inability to transition to oral loop diuretics by Day 5, and residual ultrasound congestion. The findings of the SURE-HF trial may support implementation of urinary sodium-guided and ultrasound-assisted decongestive therapy in routine heart failure management.

Interventions

• Drug Furosemide
  Intravenous loop diuretic therapy administered according to predefined treatment algorithms, including intermittent bolus administration, continuous infusion, or prolonged intermittent infusion with protocol-driven dose titration.
• Device Horiba LAQUAtwin B-722
  Portable point-of-care urinary sodium analyzer used for serial spot urinary sodium measurements to guide decongestive therapy.

Primary outcome measures

• Hierarchical Composite Endpoint of Unsuccessful Decongestion [Time frame: From randomization through hospital discharge, assessed up to 14 days.]

Secondary outcome measures (6)

• Total and Time-Specific Urinary Sodium Excretion [Time frame: 6, 24, 48, and 72 hours after initiation of intravenous loop diuretic therapy.]
• Time to Clinical Decongestion [Time frame: From initiation of intravenous loop diuretic therapy until clinical decongestion, assessed up to 14 days.]
• Length of Hospital Stay [Time frame: From hospital admission to hospital discharge, assessed up to 30 days.]
• Death or Heart Failure Rehospitalization Within 30 Days After Discharge [Time frame: From hospital discharge through 30 days after discharge.]
• Cumulative Urine Output [Time frame: From initiation of intravenous loop diuretic therapy through hospital discharge, assessed up to 14 days.]
• Proportion of Patients Achieving Predefined Natriuresis Targets [Time frame: Within 72 hours after initiation of intravenous loop diuretic therapy.]

Eligibility criteria

Inclusion criteria

• Age ≥18 years.
• Confirmed diagnosis of worsening heart failure (WHF), characterized by symptoms and signs of acute decompensation requiring hospitalization for intensification of intravenous diuretic therapy.
• Previous intake of a loop diuretic (torasemide or furosemide) in any dose for at least 2 days before hospitalization.
• Presence of clinical signs and symptoms of congestion (e.g., dyspnea, orthopnea, peripheral edema, pulmonary congestion).
• Provision of written informed consent.

Exclusion criteria

• Acute coronary syndrome within the previous 30 days.
• Acute heart failure requiring urgent invasive intervention, including cardiogenic shock or mechanical circulatory support.
• Current admission to an intensive care unit.
• Systolic blood pressure ≤90 mmHg or requirement for inotropic/vasopressor support.
• Recent use (≤48 hours) of inotropic agents affecting fluid and electrolyte balance.
• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² or requirement for renal replacement therapy.
• Hypokalemia (<3.5 mmol/L) or hyperkalemia (≥5.5 mmol/L).
• Clinically significant hyponatremia (<130 mmol/L) or hypernatremia (>150 mmol/L).
• Significant comorbidities affecting sodium-water balance (e.g., liver cirrhosis with ascites, nephrotic syndrome, severe infection or sepsis).
• Pregnancy or breastfeeding.
• Active malignancy.
• Inability to comply with the study protocol or participation in another interventional clinical trial.

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

Kazakhstan · 1 center

• West Kazakhstan Marat Ospanov Medical University — Aktobe

Publications

• Ter Maaten JM, Beldhuis IE, van der Meer P, Krikken JA, Coster JE, Nieuwland W, van Veldhuisen DJ, Voors AA, Damman K. Natriuresis-guided therapy in acute heart failure: rationale and design of the Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) trial. Eur J Heart Fail. 2022 Feb;24(2):385-392. doi: 10.1002/ejhf.2385. Epub 2022 Jan 6. PMID 34791756
• Mullens W, Damman K, Harjola VP, Mebazaa A, Brunner-La Rocca HP, Martens P, Testani JM, Tang WHW, Orso F, Rossignol P, Metra M, Filippatos G, Seferovic PM, Ruschitzka F, Coats AJ. The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019 Feb;21(2):137-155. doi: 10.1002/ejhf.1369. Epu PMID 30600580
• McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Gro PMID 34447992

Identifiers

NCT: NCT07631780 · 13/2-19-38-7 · Order №13/2-19-38-7

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗