Protocolised Natriuresis-Guided Decongestion at Different Diuretic Intensities in Acute Heart Failure

NCT07804654 | Completed

• 1 other identifier: DESTINaTE-AHF
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn how different doses of a water-removing medicine (diuretic) work in adults admitted to hospital with acute heart failure. It will also assess the safety of these treatment approaches. The main questions this study aims to answer are: Does starting with a higher or lower dose of diuretic affect how much sodium and urine the body removes during the first 24 hours? Are there differences in side effects or short-term health outcomes between the treatment approaches? Researchers will compare two treatment approaches that use urine sodium and urine output to guide diuretic treatment with standard care. Participants will receive intravenous diuretic treatment and have their urine sodium, urine output, symptoms, blood tests, and clinical outcomes assessed.

Conditions

Acute Heart Failure (AHF)

Keywords

Acute Heart Failure; Natriuresis; Furosemide; Diuresis; Sodium

Outcome Measures

Primary Outcomes (3)

• 24-Hour Urinary Sodium Excretion

  Total urinary sodium excretion during the first 24 hours after randomisation, calculated from the 24-hour urine collection and expressed in mmol.

  From randomisation to 24 hours

• 24-Hour Urine Volume

  Total urine volume collected during the first 24 hours after randomisation, expressed in litres.

  From randomisation to 24 hours

• Change From Baseline in Breathlessness Likert Score at 24 Hours

  Change in participant-reported breathlessness from baseline to 24 hours, assessed using a 5-point Likert scale. Higher scores indicate greater improvement in breathlessness.

  Baseline and 24 hours after randomisation

Secondary Outcomes (4)

• Length of Stay

  From the date of hospital admission until the date of hospital discharge, assessed up to 30 days.

• Worsening Renal Function at Discharge

  From baseline to hospital discharge, assessed up to 30 days.

• 30-Day Unplanned Heart Failure Rehospitalisation

  From hospital discharge to 30 days after discharge

• All-Cause Mortality Through 30 Days After Hospital Discharge

  From randomisation to 30 days after hospital discharge

Other Outcomes (5)

• Hypotension

  From randomisation to 24 hours

• Worsening Renal Function at 24 Hours

  Baseline and 24 hours after randomisation

• Hypokalaemia at 24 Hours

  At 24 hours after randomisation

Study Arms (3)

HIGH-dose Natriuresis-Guided Therapy

EXPERIMENTAL

Participants received protocolised HIGH-dose natriuresis-guided intravenous furosemide therapy during the first 24 hours.

Drug: Furosemide - HIGH-dose Natriuresis-Guided Strategy

LOW-dose Natriuresis-Guided Therapy

EXPERIMENTAL

Participants received protocolised LOW-dose natriuresis-guided intravenous furosemide therapy during the first 24 hours.

Drug: Furosemide - LOW-dose Natriuresis-Guided Strategy

Standard of Care

ACTIVE COMPARATOR

Participants received intravenous loop diuretic therapy according to the treating clinician's usual practice.

Drug: Loop Diuretic - Standard of Care

Interventions

Furosemide - HIGH-dose Natriuresis-Guided Strategy DRUG

Intravenous furosemide was administered according to a predefined HIGH-dose natriuresis-guided protocol during the first 24 hours. For participants not receiving chronic loop diuretic therapy, the protocol-defined 24-hour dose was 80 mg. For chronic loop diuretic users, the protocol-defined 24-hour dose was calculated as 2.5 times their total home oral daily furosemide-equivalent dose and administered intravenously in divided doses. Urinary sodium at 2 and 6 hours and urine output at 6 hours were used to guide subsequent dosing according to predefined response criteria.

Also known as: HIGH-dose

HIGH-dose Natriuresis-Guided Therapy

Furosemide - LOW-dose Natriuresis-Guided Strategy DRUG

Intravenous furosemide was administered according to a predefined LOW-dose natriuresis-guided protocol during the first 24 hours. For participants not receiving chronic loop diuretic therapy, the protocol-defined 24-hour dose was 60 mg. For chronic loop diuretic users, the protocol-defined 24-hour dose was calculated as 1.5 times their total home oral daily furosemide-equivalent dose and administered intravenously in divided doses. Urinary sodium at 2 and 6 hours and urine output at 6 hours were used to guide subsequent dosing according to predefined response criteria.

Also known as: LOW-dose

LOW-dose Natriuresis-Guided Therapy

Loop Diuretic - Standard of Care DRUG

Intravenous loop diuretic therapy was administered according to the treating clinician's usual practice. The dose and subsequent adjustment of loop diuretic therapy were determined by the treating clinical team without a protocol-mandated dosing or escalation strategy. Urinary sodium and urine output were assessed at the same study time points as in the natriuresis-guided groups, but no protocol-directed treatment adjustment was mandated based on these measurements.

Also known as: Standard of Care

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older
• Malaysian nationality
• Hospitalised with acute heart failure, either de novo acute heart failure or acute decompensated chronic heart failure
• Clinical evidence of congestion requiring intravenous loop diuretic therapy, with at least one of the following: peripheral oedema, orthopnoea, paroxysmal nocturnal dyspnoea, pulmonary crepitations, elevated jugular venous pressure, ascites, or congestive hepatomegaly
• Able to provide informed consent

You may not qualify if:

• End-stage renal disease requiring chronic dialysis
• Requirement or anticipated requirement for invasive mechanical ventilation
• Requirement or anticipated requirement for inotropic or vasopressor support
• Requirement or anticipated requirement for renal replacement therapy
• Cardiogenic shock or systolic blood pressure below 100 mmHg
• Pregnancy or breastfeeding
• Known hypersensitivity to furosemide

Sponsors & Collaborators

• Universiti Teknologi Mara: lead

Study Sites (1)

Hospital Al-Sultan Abdullah, Universiti Teknologi MARA

Shah Alam, Selangor, 42300, Malaysia

Location

Related Publications (12)

• Al-Shammari AS, Hamzah KA, Masanabadi M, Asif M, Budhiraja M, Shafi N, Hamed BM, Kurmasha YH, Shweliya MA, Sattar Y. Urinary sodium-guided diuretic therapy in acute decompensated heart failure: A grade assessed systematic review and meta-analysis with trial sequential analysis. Curr Probl Cardiol. 2026 May;51(5):103272. doi: 10.1016/j.cpcardiol.2026.103272. Epub 2026 Jan 20.

  PMID: 41571219 BACKGROUND

• Meekers E, Dauw J, Ter Maaten JM, Martens P, Nijst P, Verbrugge FH, Van Es M, Erzeel J, Damman K, Trullas JC, Dupont M, Mullens W. Urinary sodium analysis: The key to effective diuretic titration? European Journal of Heart Failure expert consensus document. Eur J Heart Fail. 2025 Jun;27(6):940-949. doi: 10.1002/ejhf.3632. Epub 2025 Feb 27.

  PMID: 40017142 BACKGROUND

• ter Maaten JM, Valente MA, Damman K, Hillege HL, Navis G, Voors AA. Diuretic response in acute heart failure-pathophysiology, evaluation, and therapy. Nat Rev Cardiol. 2015 Mar;12(3):184-92. doi: 10.1038/nrcardio.2014.215. Epub 2015 Jan 6.

  PMID: 25560378 BACKGROUND

• Wan Ahmad WA, Abdul Ghapar AK, Zainal Abidin HA, Karthikesan D, Ross NT, S K Abdul Kader MA, Loch A, Mahendran K, Ramli AW, Ong TK, Mohd Amin NH, Lee CY, Che Hassan HH, Zainal Abidin SK, Liew HB, Ho WS, Mohd Ghazi A. Characteristics of patients admitted with heart failure: Insights from the first Malaysian Heart Failure Registry. ESC Heart Fail. 2024 Apr;11(2):727-736. doi: 10.1002/ehf2.14608. Epub 2023 Dec 22.

  PMID: 38131217 BACKGROUND

• Damman K, Ter Maaten JM, Coster JE, Krikken JA, van Deursen VM, Krijnen HK, Hofman M, Nieuwland W, van Veldhuisen DJ, Voors AA, van der Meer P. Clinical importance of urinary sodium excretion in acute heart failure. Eur J Heart Fail. 2020 Aug;22(8):1438-1447. doi: 10.1002/ejhf.1753. Epub 2020 Feb 22.

  PMID: 32086996 BACKGROUND

• 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 Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.

  PMID: 34447992 BACKGROUND

• Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1.

  PMID: 35363499 BACKGROUND

• Felker GM, Ellison DH, Mullens W, Cox ZL, Testani JM. Diuretic Therapy for Patients With Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Mar 17;75(10):1178-1195. doi: 10.1016/j.jacc.2019.12.059.

  PMID: 32164892 BACKGROUND

• 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. Epub 2019 Jan 1.

  PMID: 30600580 BACKGROUND

• Dauw J, Charaya K, Lelonek M, Zegri-Reiriz I, Nasr S, Paredes-Paucar CP, Borbely A, Erdal F, Benkouar R, Cobo-Marcos M, Barge-Caballero G, George V, Zara C, Ross NT, Barker D, Lekhakul A, Frea S, Ghazi AM, Knappe D, Doghmi N, Klincheva M, Fialho I, Bovolo V, Findeisen H, Alhaddad IA, Galluzzo A, de la Espriella R, Tabbalat R, Miro O, Singh JS, Nijst P, Dupont M, Martens P, Mullens W. Protocolized Natriuresis-Guided Decongestion Improves Diuretic Response: The Multicenter ENACT-HF Study. Circ Heart Fail. 2024 Jan;17(1):e011105. doi: 10.1161/CIRCHEARTFAILURE.123.011105. Epub 2024 Jan 5.

  PMID: 38179728 BACKGROUND

• Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419.

  PMID: 21366472 BACKGROUND

• Ter Maaten JM, Beldhuis IE, van der Meer P, Krikken JA, Postmus D, Coster JE, Nieuwland W, van Veldhuisen DJ, Voors AA, Damman K. Natriuresis-guided diuretic therapy in acute heart failure: a pragmatic randomized trial. Nat Med. 2023 Oct;29(10):2625-2632. doi: 10.1038/s41591-023-02532-z. Epub 2023 Aug 28.

  PMID: 37640861 BACKGROUND

MeSH Terms

Interventions

Contraceptives, Oral; Standard of Care

Intervention Hierarchy (Ancestors)

Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Nor Afiqah Mohd Sebri, MB BCh BAO

  Universiti Teknologi Mara

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Officer and MMed Internal Medicine Postgraduate Student

Study Record Dates

• First Submitted: August 27, 2026
• First Posted: September 4, 2026
• Study Start: January 1, 2026
• Primary Completion: July 1, 2026
• Study Completion: July 31, 2026
• Last Updated: September 4, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)