Acetazolamide Versus Dapagliflozin in Acute Decompensated Heart Failure Patients

August 1, 2024 updated by: Mahmoud I Mostafa, Helwan University

The goal of this clinical trial is to compare the effectiveness of acetazolamide versus dapagliflozin as an add-on in treating acute decompensated heart failure (ADHF) in adult patients with clinical signs of volume overload requiring intravenous loop diuretics. It will also assess the safety of these drugs when added to standard care. The main questions it aims to answer are:

  • Does acetazolamide or dapagliflozin lead to a greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels?
  • Which drug results in better loop diuretic efficiency, as measured by weight loss per 40 mg of intravenous furosemide or equivalent? We will compare acetazolamide to dapagliflozin, both added to standard intravenous loop diuretic therapy, to see which is more effective in decongesting patients with ADHF.

Participants will:

  • Take either acetazolamide or dapagliflozin orally every day for 3 days
  • Receive intravenous loop diuretics as part of standard care
  • Undergo regular assessments of heart failure symptoms, weight, and laboratory tests
  • Be followed up until hospital discharge and for 30 days after starting the study

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

A. Study design

  • Prospective, open-label, randomized, two-armed parallel comparator study.
  • Participants recruited in the study must provide written informed consent after obtaining ethical approval from ethics committee.

B. Study settings Critical Care Medicine Department - Cairo University Hospitals. C. Population of study Adult patients who are admitted to Critical Care Medicine Department - Cairo University Hospitals because of acute decompensated heart failure will be screened for inclusion into the study. Patients who have at least one clinical sign of volume overload (i.e., edema, pleural effusion, or ascites) and ECHO-confirmed HF at screening will be included in the study.

D.Treatment :

I.V loop diuretics

At the moment of randomization, oral loop diuretics are stopped. Patients need to empty their bladder before administration of the first dose of loop diuretics and all will receive an intravenous loop diuretic at double the oral maintenance dose, administered as a single bolus immediately after randomization and split into more than two doses (separated by ≥6 hours) on each of the next 2 days.

Group 1: Oral Acetazolamide Together with the initial bolus dose of loop diuretics, patients will receive 500 mg oral Acetazolamide. Time of subsequent dose of acetazolamide taken once daily will start together with the first maintenance loop diuretic dose.

Group 2: Oral Dapagliflozin Together with the initial dose of loop diuretics, patients will receive 10 mg Dapagliflozin.

Time of subsequent dose of Dapagliflozin taken once daily will start together with the first maintenance loop diuretic dose.

E. Study tools

Modified ADVOR Score The modified ADVOR congestion score will be calculated on a scale from 0 to 10 based on 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. This score will be calculated for each included patient before the administration of the first dose of diuretics during the treatment phase, at the end of the study.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 3

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

Study Locations

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:

  • Male or female patients of 18 years of age or older.
  • An elective or emergency hospital admission with clinical diagnosis of decompensated HF 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).
  • Assessed LVEF by any imaging technique; i.e. echocardiography, catheterization, nuclear scan magnetic resonance imaging within 12 months of inclusion.

Exclusion Criteria:

  • The receipt of acetazolamide maintenance therapy.
  • Receipt of an SGLT2 inhibitor in the 48 hours before randomization.
  • An estimated glomerular filtration rate (eGFR) <20 mL/min/1.73 m2.
  • Use of any non-protocol defined diuretic agent with the exception of mineralocorticoid receptor antagonists during the treatment phase of the study. Thiazides, metolazone, indapamide and amiloride should be stopped upon study inclusion. If patient is taking a combination drug including a thiazide-type diuretic, the thiazide-type diuretic should be stopped.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Acetazolamide + Standard Care

Participants in this arm will receive:

  1. Acetazolamide: 500 mg orally, once daily for 3 days

  2. Intravenous loop diuretics: Administered at double the oral maintenance dose, given as follows:

    • Initial dose: Single bolus immediately after randomization
    • Subsequent doses: Split into two or more doses (separated by ≥6 hours) on each of the next 2 days The specific loop diuretic used (e.g., furosemide) will be determined by the treating physician based on the patient's prior medication regimen and clinical status.
Drug: Acetazolamide
Patients will receive acetazolamide 500 mg once daily for 3 days as add on therapy to IV loop diuretics
Other Names:
  • Cidamix
Active Comparator: Dapagliflozin + Standard Care

Participants in this arm will receive:

  1. Dapagliflozin: 10 mg orally, once daily for 3 days
  2. Intravenous loop diuretics: Administered as described in Arm 1
Drug: Dapagliflozin 10mg
patient will receive oral dapagliflozin 10 mg once daily for 3 days as add on therapy to IV loop diuretics
Other Names:
  • Forxiga

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
N-terminal pro-B-type natriuretic peptide (NT-proBNP)
Time Frame: From baseline to day 5 or intensive care unit (ICU) discharge, whichever occurs first
Absolute change in NT-proBNP levels from baseline to end of study period
From baseline to day 5 or intensive care unit (ICU) discharge, whichever occurs first
calculating of weight loss Loop diuretic efficiency
Time Frame: 72 hours from initiation of treatment
Weight loss (in kg) per 40 mg of intravenous furosemide or equivalent dose of other loop diuretics
72 hours from initiation of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with Successful decongestion
Time Frame: 72 hours from initiation of treatment
Proportion of patients achieving an ADVOR Score ≤ 1 without the need for escalating diuretic strategy (defined as doubling loop diuretic dose, addition of chlorthalidone, or ultrafiltration)
72 hours from initiation of treatment
Duration of the index hospital admission
Time Frame: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 100 weeks
Number of days from randomization until the date of discharge
From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 100 weeks
30-day mortality
Time Frame: Up to 30 days
Proportion of patients who die from any cause within 30 days of randomization
Up to 30 days
Cumulative dose of intravenous loop diuretics
Time Frame: 5 days
Total milligrams of intravenous furosemide or equivalent dose of other loop diuretics administered
5 days
Incidence of treatment-related metabolic acidosis
Time Frame: 5 days
Proportion of patients developing metabolic acidosis requiring sodium bicarbonate (NaHCO3) supplementation
5 days
percent of worsening renal failure (WRF)
Time Frame: up to 4 weeks
Proportion of patients experiencing either: a) An increase in serum creatinine > 0.3 mg/dL from baseline, or b) A decrease in estimated glomerular filtration rate (eGFR) > 20% from baseline
up to 4 weeks

Collaborators and Investigators

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

Sponsor

Helwan University

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)

August 24, 2024

Primary Completion (Estimated)

August 1, 2025

Study Completion (Estimated)

September 1, 2025

Study Registration Dates

First Submitted

June 29, 2024

First Submitted That Met QC Criteria

July 30, 2024

First Posted (Actual)

August 2, 2024

Study Record Updates

Last Update Posted (Estimated)

August 5, 2024

Last Update Submitted That Met QC Criteria

August 1, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Acetazolamide vs Dapa in ADHF

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

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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