Add-on Diuretics in Acute Decompensated Heart Failure

Clinical Study Comparing Empagliflozin, Acetazolamide, and Metolazone as Add-on Therapies to Loop Diuretics in Acute Decompensated Heart Failure

The aim of this study is to compare the efficacy and safety of empagliflozin, acetazolamide, and metolazone as add-on therapies to loop diuretics in patients with acute decompensated heart failure.

Study Overview

• Status: Recruiting
• Conditions: Acute Decompensated Heart Failure
• Intervention / Treatment: Drug: empagliflozin; Drug: Acetazolamide; Drug: metolazone

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dalia A Gomaa, MSc in clinical pharmacy; Phone Number: +20+01063410525; Email: dalia_gomaa@pharm.tanta.edu.eg
• Study Contact Backup: Name: Dalia R El-Afify, Associate professor; Phone Number: +20+01006831093; Email: dalia.mohamed1@pharm.tanta.edu.eg

Study Locations

• Egypt
  • Tanta, Egypt
    • Recruiting
    • Tanta University
    • Contact: Dalia A Gomaa, MSc in clinical pharmacy; Phone Number: 02+01063410525; Email: dalia_gomaa@pharm.tanta.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients older than 18 years.
2. Hospital admission with clinical diagnosis of acute decompensated heart failure with at least one clinical sign of volume overload (e.g. edema, ascites confirmed by echography or pleural effusion confirmed by chest X-ray or echography).

Exclusion Criteria:

1. Type 1 diabetes.
2. Chronic kidney disease with estimated glomerular filtration rate (eGFR) <30 mL/min per 1.73 m² or end-stage kidney failure with the need for chronic dialysis treatment.
3. A systolic blood pressure of less than 90 mmHg.
4. Cardiogenic shock.
5. Receipt of acetazolamide maintenance therapy.
6. Receipt of an SGLT2 inhibitor, thiazide, or thiazide-like diuretic in the 48 hrs before randomization.
7. Any cause of heart failure leading to decompensation that will need urgent management (eg, acute coronary syndrome, unstable arrhythmias, acute pulmonary embolism).
8. Pregnant or breastfeeding women.
9. Moderate to severe anemia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Empagliflozin group; will include 22 patients who will receive 10 mg oral empagliflozin administered simultaneously with the first dose of loop diuretics each day for 3 days	Drug: empagliflozin; Empagliflozin may augment the natriuretic and aquaretic actions of loop diuretics in patients with acute decompensated heart failure and it does not typically cause electrolyte disturbances and has been shown to improve outcomes in patients with heart failure
Active Comparator: Acetazolamide group; will include 22 patients who will receive 500 mg oral acetazolamide administered simultaneously with the first dose of loop diuretics each day for 3 days	Drug: Acetazolamide; Acetazolamide can augment the action of loop diuretics in patients with acute decompensated heart failure
Active Comparator: Metolazone group; will include 22 patients who will receive 5 mg oral metolazone administered simultaneously with the first dose of loop diuretics each day for 3 days	Drug: metolazone; Metolazone can augment the action of loop diuretics in patients with acute decompensated heart failure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The cumulative urine output measured over 3 days	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
- The change in serum level of N-terminal pro-brain natriuretic peptide (NT-proBNP)	Blood samples will be collected at baseline and after 4 days	4 days
The change in serum level of Soluble suppression of tumorigenicity 2 (sST2)	Blood samples will be collected at baseline and after 4 days	4 days
The change in urinary level of Tissue inhibitor of metalloproteinases-2 (TIMP-2 )	Urine samples will be collected at baseline and after 3 days	3 days
The change in urinary level of Insulin-like growth factor-binding protein 7 (IGFBP7)	Urine samples will be collected at baseline and after 3 days	3 days
30-day mortality	Proportion of patients who die within 30 days of randomization	up to 30 days
Proportion of patients achieving an ADVOR Score ≤ 1 without the need for escalating diuretic strategy	the treating physician will calculate the congestion score, on a scale from 0 to 10 on the basis of the sum of scores for the degree of edema (0 to 4), pleural effusion (0 to 3), and ascites (0 to 3), with higher scores indicating a worse condition on all scales	3 days

Collaborators and Investigators

• Sponsor: Tanta University
• Investigators: Principal Investigator: Dalia A Gomaa, MSc in clinical pharmacy, Tanta University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: January 19, 2026
• First Submitted That Met QC Criteria: January 19, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Acetazolamide; Empagliflozin; Acute heart failure; Metolazone; Add-on therapies to Loop diuretics
• Additional Relevant MeSH Terms: Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Azoles; Amides; Thiadiazoles; Sulfonamides; Sulfones; Quinazolinones; Quinazolines; Acetazolamide; Metolazone; empagliflozin
• Other Study ID Numbers: Acute Heart Failure 2026

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
• product manufactured in and exported from the U.S.: No