SGLT-2 Inhibitor and High-Dose Furosemide Plus Small-Volume Hypertonic Saline Solution in Acute HF

NCT06442280 | Not Yet Recruiting Phase 4

• 1 other identifier: UPalermo7
• Study Type: interventional
• Target: 544
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the current investigation is to demonstrate the efficacy of high-dose furosemide plus small-volume hypertonic saline solution and a Sodium-Glucose cotransporter-2 (SGLT-2) inhibitor among patients admitted for acute exacerbation of heart failure, in determining a significant increase in diuresis and natriuresis. It is also accompanied by a rapid reduction in body weight and a substantial decrease in hospitalization length without compromising renal function.

Conditions

Heart Failure Acute; Diabetes Type 2; Heart Failure With Reduced Ejection Fraction; Heart Failure With Preserved Ejection Fraction

Keywords

Acute Heart Failure; Diabetes Type 2; SGLT-2 inhibitors; Furosemide; Hypertonic Solution

Outcome Measures

Primary Outcomes (3)

• Diuresis from the baseline and up to 1 week

  Daily urinary volume (mL) are detected by chemiluminescence immunoassay.

  an average of 1 week

• Natriuresis from the baseline and up to 1 week

  Daily natriuresis (mEq/L) are detected by chemiluminescence immunoassay.

  an average of 1 week

• Length of hospital stay

  Duration of hospital stay in days.

  immediately after the intervention

Secondary Outcomes (1)

• Kidney function during treatment

  an average of 1 week

Study Arms (4)

Dapa-Tonic

EXPERIMENTAL

This group will undergo a 15-minute intravenous infusion of furosemide combined with hypertonic saline solutions (100 mL) twice daily, severe water restriction (\< 500 mL), and SGLT2 inhibitors (Dapagliflozin).

Drug: Dapagliflozin tablet; Drug: Hypertonic Saline Solution, 1 Ml

Tonic-Placebo

PLACEBO COMPARATOR

This group will undergo a 15-minute intravenous infusion of furosemide combined with hypertonic saline solutions (100 mL) twice daily along with severe water restriction (\< 500 mL).

Drug: Hypertonic Saline Solution, 1 Ml

Furosemide-Placebo

PLACEBO COMPARATOR

This group will undergo intravenous furosemide twice daily and severe water restriction (\< 500 mL) without hypertonic saline solutions.

Drug: Furosemide Injection

Dapa-Furo

ACTIVE COMPARATOR

This group will undergo intravenous furosemide without hypertonic saline solutions twice daily, severe water restriction (\< 500 mL), and SGLT2 inhibitors (Dapagliflozin).

Drug: Dapagliflozin tablet; Drug: Furosemide Injection

Interventions

Dapagliflozin tablet DRUG

Dapagliflozin 10 mg 1 tablet once daily

Also known as: SGLT2 inhibitor

Dapa-Furo; Dapa-Tonic

Hypertonic Saline Solution, 1 Ml DRUG

Intravenous infusion of furosemide combined with hypertonic saline solutions (100 mL) twice daily

Also known as: Hypertonic Solution, Saline

Dapa-Tonic; Tonic-Placebo

Furosemide Injection DRUG

Furosemide 20 mg

Also known as: FUROSEMIDE

Dapa-Furo; Furosemide-Placebo

Eligibility Criteria

• Age: 40 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• acute heart failure;
• diabetes type 2.

You may not qualify if:

• low estimated glomerular filtration rate;
• hypernatremia;
• diabetes type 1;
• non-cardiac causes of dyspnea;
• cardiogenic shock;
• recent occurrence of Acute Coronary Syndrome;
• ketoacidosis;
• hyperosmolar hyperglycemic syndrome.

Sponsors & Collaborators

• University of Palermo: lead

Related Publications (12)

• 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 RESULT

• Liszkowski M, Nohria A. Rubbing salt into wounds: hypertonic saline to assist with volume removal in heart failure. Curr Heart Fail Rep. 2010 Sep;7(3):134-9. doi: 10.1007/s11897-010-0018-4.

  PMID: 20607462 RESULT

• Arrigo M, Jessup M, Mullens W, Reza N, Shah AM, Sliwa K, Mebazaa A. Acute heart failure. Nat Rev Dis Primers. 2020 Mar 5;6(1):16. doi: 10.1038/s41572-020-0151-7.

  PMID: 32139695 RESULT

• Parrinello G, Di Pasquale P, Torres D, Cardillo M, Schimmenti C, Lupo U, Iatrino R, Petrantoni R, Montaina C, Giambanco S, Paterna S. Troponin I release after intravenous treatment with high furosemide doses plus hypertonic saline solution in decompensated heart failure trial (Tra-HSS-Fur). Am Heart J. 2012 Sep;164(3):351-7. doi: 10.1016/j.ahj.2012.05.025. Epub 2012 Aug 17.

  PMID: 22980301 RESULT

• Parrinello G, Paterna S, Di Pasquale P, Torres D, Mezzero M, Cardillo M, Fasullo S, La Rocca G, Licata G. Changes in estimating echocardiography pulmonary capillary wedge pressure after hypersaline plus furosemide versus furosemide alone in decompensated heart failure. J Card Fail. 2011 Apr;17(4):331-9. doi: 10.1016/j.cardfail.2010.11.003. Epub 2010 Dec 24.

  PMID: 21440872 RESULT

• Paterna S, Di Pasquale P, Parrinello G, Fornaciari E, Di Gaudio F, Fasullo S, Giammanco M, Sarullo FM, Licata G. Changes in brain natriuretic peptide levels and bioelectrical impedance measurements after treatment with high-dose furosemide and hypertonic saline solution versus high-dose furosemide alone in refractory congestive heart failure: a double-blind study. J Am Coll Cardiol. 2005 Jun 21;45(12):1997-2003. doi: 10.1016/j.jacc.2005.01.059.

  PMID: 15963399 RESULT

• Xie Y, Wei Y, Li D, Pu J, Ding H, Zhang X. Mechanisms of SGLT2 Inhibitors in Heart Failure and Their Clinical Value. J Cardiovasc Pharmacol. 2023 Jan 1;81(1):4-14. doi: 10.1097/FJC.0000000000001380.

  PMID: 36607775 RESULT

• Solomon SD, Vaduganathan M, Claggett BL, de Boer RA, DeMets D, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CSP, Martinez F, Shah SJ, Belohlavek J, Chiang CE, Willem Borleffs CJ, Comin-Colet J, Dobreanu D, Drozdz J, Fang JC, Alcocer Gamba MA, Al Habeeb W, Han Y, Cabrera Honorio JW, Janssens SP, Katova T, Kitakaze M, Merkely B, O'Meara E, Kerr Saraiva JF, Tereschenko SN, Thierer J, Vardeny O, Verma S, Vinh PN, Wilderang U, Zaozerska N, Lindholm D, Petersson M, McMurray JJV. Baseline Characteristics of Patients With HF With Mildly Reduced and Preserved Ejection Fraction: DELIVER Trial. JACC Heart Fail. 2022 Mar;10(3):184-197. doi: 10.1016/j.jchf.2021.11.006.

  PMID: 35241246 RESULT

• Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.

  PMID: 32970396 RESULT

• Ostermann M, Bellomo R, Burdmann EA, Doi K, Endre ZH, Goldstein SL, Kane-Gill SL, Liu KD, Prowle JR, Shaw AD, Srisawat N, Cheung M, Jadoul M, Winkelmayer WC, Kellum JA; Conference Participants. Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int. 2020 Aug;98(2):294-309. doi: 10.1016/j.kint.2020.04.020. Epub 2020 Apr 26.

  PMID: 32709292 RESULT

• Clark WF, Sontrop JM, Macnab JJ, Suri RS, Moist L, Salvadori M, Garg AX. Urine volume and change in estimated GFR in a community-based cohort study. Clin J Am Soc Nephrol. 2011 Nov;6(11):2634-41. doi: 10.2215/CJN.01990211. Epub 2011 Sep 1.

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• Oh SW, Han SY. Loop Diuretics in Clinical Practice. Electrolyte Blood Press. 2015 Jun;13(1):17-21. doi: 10.5049/EBP.2015.13.1.17. Epub 2015 Jun 30.

  PMID: 26240596 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin; Sodium-Glucose Transporter 2 Inhibitors; Saline Solution, Hypertonic; Furosemide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Hypertonic Solutions; Solutions; Pharmaceutical Preparations; Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Study Officials

• Giuseppe Miceli, PhD

  A.O.U.P. Paolo Giaccone Palermo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antonino Tuttolomondo, Professor

CONTACT

+39 091 6552115; bruno.tuttolomondo@unipa.it

Giuseppe Miceli, PhD

CONTACT

+39 0916552197; miceli.gpp@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Patients will be categorized into 4 groups: the first group will undergo 15 minutes intravenous infusion of furosemide combined with hypertonic saline solution (100 mL) twice daily along with severe water restriction (\< 500 mL); the second group will receive intravenous furosemide as a bolus twice daily and severe water restriction (\< 500 mL) without hypertonic saline solution; the third group will undergo 15 minutes intravenous infusion of furosemide combined with hypertonic saline solution (100 mL) twice daily, severe water restriction (\< 500 mL), and SGLT2 inhibitors (Dapagliflozin); the fourth group will receive intravenous furosemide as a bolus without hypertonic saline solution twice daily, severe water restriction (\< 500 mL), and SGLT2 inhibitors (Dapagliflozin).

Study Record Dates

• First Submitted: January 19, 2024
• First Posted: June 4, 2024
• Study Start: June 1, 2024
• Primary Completion: January 31, 2026
• Study Completion: March 30, 2026
• Last Updated: June 6, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share