Clinical trial NCT06535529: Acetazolamide Versus Dapagliflozin in Acute Decompensated Heart Failure Patients
Official title: Acetazolamide Versus Dapagliflozin in Acute Decompensated Heart Failure Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acute Decompensated Heart Failure
Keywords: Acute Heart failure
ADHF
Acetazolamide
SGLT2 inhibitors
SGLT2i
Lead sponsor: Helwan University
Sponsor class: OTHER
First posted: 2024-08-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, open-label, randomized, two-armed parallel comparator study.
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: N-terminal pro-B-type natriuretic peptide (NT-proBNP)
timeFrame: From baseline to day 5 or intensive care unit (ICU) discharge, whichever occurs first
measure: calculating of weight loss Loop diuretic efficiency
timeFrame: 72 hours from initiation of treatment
Secondary outcomes:
measure: Number of Participants with Successful decongestion
timeFrame: 72 hours from initiation of treatment
measure: Duration of the index hospital admission
timeFrame: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 100 weeks
measure: 30-day mortality
timeFrame: Up to 30 days
measure: Cumulative dose of intravenous loop diuretics
timeFrame: 5 days
measure: Incidence of treatment-related metabolic acidosis
timeFrame: 5 days
measure: percent of worsening renal failure (WRF)
timeFrame: up to 4 weeks
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Critical Care Medicine Department - Cairo University Hospitals.
Study officials:
References:
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