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

June 4, 2024 updated by: Antonino Tuttolomondo, University of Palermo

Enhanced Diuresis and Natriuresis in Acute Decompensated Heart Failure Patients Treated With SGLT-2 Inhibitor and High-Dose Furosemide Plus Small-Volume Hypertonic Saline Solution: A Clinical Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

All enrolled patients will undergo a comprehensive physical examination post-randomization. This examination will involve a meticulous assessment of congestive heart failure (CHF) indicators, encompassing the measurement of bodyweight (BW) (taken in the morning before breakfast), supine and standing blood pressure (BP [average of 3 readings]), and heart rate (HR). Fasting blood samples will be collected daily throughout the hospital stay to ascertain serum laboratory parameters (creatinine, sodium, potassium, and N-terminal pro b-type natriuretic peptide) until achieving a clinically stabilized condition. Urine output will be measured daily, also to detect creatinine, sodium, potassium urinary levels and glycosuria. Additionally, an electrocardiogram and echocardiogram (to derive EF using the modified Simpson rule with 2 cross-sectional views [4- and 2-chamber apical views], right atrium volume (RA volume, ml/m2), left atrial volume (LA volume ml/m2), inferior vena cava diameter (IVC diameter, cm), interventricular septum thickness at end-diastole (IVSd, cm), right ventricular basal diameter at end-diastole (RVD1 basal, mm), right ventricular mid diameter at end-diastole (RVD2 mid, mm), right ventricular longitudinal diameter at end-diastole (RVD3 long, mm), right ventricular outflow tract at proximal and distal (RVOT prox and distal, mm), fractional area change (FAC, %), E wave dominant (m/s), A wave dominant (m/s), tricuspid valve E/A wave ratio (E/ATrV), tissue Doppler echocardiography (TDE, ms), eak velocity in early diastole of tricuspid annulus (TDI) (m/s), tricuspid valve e'/a' ratio (TDI, m/s), peak systolic velocity tricuspid annulus (Pulsed TDI, m/s) will be conducted prior to hospital discharge.

Patients will be categorized into 4 groups: the first group will undergo 15 minutes intravenous infusion of furosemide combined with hypertonic saline solutions (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 solutions; the third group will undergo 15 minutes intravenous infusion of furosemide combined with hypertonic saline solutions (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 solutions twice daily, severe water restriction (< 500 mL), and SGLT2 inhibitors (Dapagliflozin). The groups will maintain a normal sodium intake (120 mmol/day). The daily furosemide dosage will be determined based on diuretic requirements, urinary output, BP readings, and the severity of congestion signs and symptoms. The hypertonic saline solutions dosage for each patient (in groups 1 and 3) will be determined following these guidelines: for serum Na values of 125 milliequivalent/L, the hypertonic saline solutions concentration will be 4.6%; for serum Na values between 126 and 135 milliequivalent/L, the hypertonic saline solutions concentration will be 3.5%; and for serum Na values of 135 milliequivalent/L, the hypertonic saline solutions concentration will range between 1.4% and 2.4%. Throughout the study period, patients diagnosed with Heart Failure with Reduced Ejection Fraction (HFrEF) will receive angiotensin converting enzyme inhibitors, sartans, angiotensin receptor-neprilysin inhibitors, beta blockers, and mineralocorticoid inhibitors. The objective is to optimize heart failure therapy in alignment with the most recent European Society of Cardiology guidelines published in August 2023. Daily, there will be meticulous monitoring of body weight (in the morning before breakfast) and 24-hour urinary volume measurements. Serum and urinary laboratory parameters will be assessed daily until achieving a clinically stabilized condition, defined as a shift in New York Heart Association functional class to at least second b and reaching the ideal body weight calculated via the Lorenz formula. Upon attaining this clinically stabilized state, intravenous administration of furosemide and hypertonic saline solutions will cease, transitioning to oral furosemide administration, while maintaining the unchanged optimal therapy post-discharge according to the standard protocol.

Study Type

Interventional

Enrollment (Estimated)

544

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • acute heart failure;
  • diabetes type 2.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dapa-Tonic
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
Dapagliflozin 10 mg 1 tablet once daily
Other Names:
  • SGLT2 inhibitor
Drug: Hypertonic Saline Solution, 1 Ml
Intravenous infusion of furosemide combined with hypertonic saline solutions (100 mL) twice daily
Other Names:
  • Hypertonic Solution, Saline
Placebo Comparator: Tonic-Placebo
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
Intravenous infusion of furosemide combined with hypertonic saline solutions (100 mL) twice daily
Other Names:
  • Hypertonic Solution, Saline
Placebo Comparator: Furosemide-Placebo
This group will undergo intravenous furosemide twice daily and severe water restriction (< 500 mL) without hypertonic saline solutions.
Drug: Furosemide Injection
Furosemide 20 mg
Other Names:
  • FUROSEMIDE
Active Comparator: Dapa-Furo
This group will undergo intravenous furosemide without hypertonic saline solutions twice daily, severe water restriction (< 500 mL), and SGLT2 inhibitors (Dapagliflozin).
Drug: Dapagliflozin tablet
Dapagliflozin 10 mg 1 tablet once daily
Other Names:
  • SGLT2 inhibitor
Drug: Furosemide Injection
Furosemide 20 mg
Other Names:
  • FUROSEMIDE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diuresis from the baseline and up to 1 week
Time Frame: an average of 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
Time Frame: an average of 1 week
Daily natriuresis (mEq/L) are detected by chemiluminescence immunoassay.
an average of 1 week
Length of hospital stay
Time Frame: immediately after the intervention
Duration of hospital stay in days.
immediately after the intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Kidney function during treatment
Time Frame: an average of 1 week
Daily evaluation of creatinine (mg/dL).
an average of 1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Palermo

Investigators

  • Principal Investigator: Giuseppe Miceli, PhD, A.O.U.P. Paolo Giaccone Palermo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2024

Primary Completion (Estimated)

January 31, 2026

Study Completion (Estimated)

March 30, 2026

Study Registration Dates

First Submitted

January 19, 2024

First Submitted That Met QC Criteria

June 2, 2024

First Posted (Actual)

June 4, 2024

Study Record Updates

Last Update Posted (Actual)

June 6, 2024

Last Update Submitted That Met QC Criteria

June 4, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPalermo7

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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