Acetazolamide Versus Dapagliflozin in Acute Decompensated Heart Failure Patients

NCT06535529 | Recruiting Phase 3

• 1 other identifier: Acetazolamide vs Dapa in ADHF
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Conditions

Acute Decompensated Heart Failure

Keywords

Acute Heart failure; ADHF; Acetazolamide; SGLT2 inhibitors; SGLT2i

Outcome Measures

Primary Outcomes (2)

• N-terminal pro-B-type natriuretic peptide (NT-proBNP)

  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

  Weight loss (in kg) per 40 mg of intravenous furosemide or equivalent dose of other loop diuretics

  72 hours from initiation of treatment

Secondary Outcomes (6)

• Number of Participants with Successful decongestion

  72 hours from initiation of treatment

• Duration of the index hospital admission

  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

  Up to 30 days

• Cumulative dose of intravenous loop diuretics

  5 days

• Incidence of treatment-related metabolic acidosis

  5 days

Study Arms (2)

Acetazolamide + Standard Care

ACTIVE COMPARATOR

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

Dapagliflozin + Standard Care

ACTIVE COMPARATOR

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

Interventions

Acetazolamide DRUG

Patients will receive acetazolamide 500 mg once daily for 3 days as add on therapy to IV loop diuretics

Also known as: Cidamix

Acetazolamide + Standard Care

Dapagliflozin 10mg DRUG

patient will receive oral dapagliflozin 10 mg once daily for 3 days as add on therapy to IV loop diuretics

Also known as: Forxiga

Dapagliflozin + Standard Care

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Helwan University: lead

Study Sites (1)

Critical Care Medicine Department - Cairo University Hospitals.

Cairo, Egypt

RECRUITING

Related Publications (8)

• Mullens W, Verbrugge FH, Nijst P, Martens P, Tartaglia K, Theunissen E, Bruckers L, Droogne W, Troisfontaines P, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M. Rationale and design of the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial. Eur J Heart Fail. 2018 Nov;20(11):1591-1600. doi: 10.1002/ejhf.1307. Epub 2018 Sep 21.

  PMID: 30238574 BACKGROUND

• Mullens W, Dauw J, Martens P, Verbrugge FH, Nijst P, Meekers E, Tartaglia K, Chenot F, Moubayed S, Dierckx R, Blouard P, Troisfontaines P, Derthoo D, Smolders W, Bruckers L, Droogne W, Ter Maaten JM, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M; ADVOR Study Group. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022 Sep 29;387(13):1185-1195. doi: 10.1056/NEJMoa2203094. Epub 2022 Aug 27.

  PMID: 36027559 BACKGROUND

• Mullens W, Schulze PC, Westphal J, Bogoviku J, Bauersachs J. Great debate: in patients with decompensated heart failure, acetazolamide in addition to loop diuretics is the first choice. Eur Heart J. 2023 Jun 25;44(24):2159-2169. doi: 10.1093/eurheartj/ehad266.

  PMID: 37207453 BACKGROUND

• Malik BA, Nnodebe I, Fayaz A, Inayat H, Murtaza SF, Umer M, Zaidi SAT, Amin A. Effect of Acetazolamide as Add-On Diuretic Therapy in Patients With Heart Failure: A Meta-Analysis. Cureus. 2023 Apr 18;15(4):e37792. doi: 10.7759/cureus.37792. eCollection 2023 Apr.

  PMID: 37213994 BACKGROUND

• Sabina M, Barakat Z, Feliciano A, Lamb A, Alsamman MM. Unlocking the Potential of Acetazolamide: A Literature Review of an Adjunctive Approach in Heart Failure Management. J Clin Med. 2024 Jan 4;13(1):288. doi: 10.3390/jcm13010288.

  PMID: 38202295 BACKGROUND

• Kosiorek A, Urban S, Detyna J, Biegus J, Hurkacz M, Zymlinski R. Diuretic, natriuretic, and chloride-regaining effects of oral acetazolamide as an add-on therapy for acute heart failure with volume overload: a single-center, prospective, randomized study. Pol Arch Intern Med. 2023 Dec 21;133(12):16526. doi: 10.20452/pamw.16526. Epub 2023 Jul 6.

  PMID: 37415505 BACKGROUND

• Siddiqi AK, Maniya MT, Alam MT, Ambrosy AP, Fudim M, Greene SJ, Khan MS. Acetazolamide as an Adjunctive Diuretic Therapy for Patients with Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis. Am J Cardiovasc Drugs. 2024 Mar;24(2):273-284. doi: 10.1007/s40256-024-00633-9. Epub 2024 Feb 28.

  PMID: 38416359 BACKGROUND

• Cox ZL, Collins SP, Hernandez GA, McRae AT 3rd, Davidson BT, Adams K, Aaron M, Cunningham L, Jenkins CA, Lindsell CJ, Harrell FE Jr, Kampe C, Miller KF, Stubblefield WB, Lindenfeld J. Efficacy and Safety of Dapagliflozin in Patients With Acute Heart Failure. J Am Coll Cardiol. 2024 Apr 9;83(14):1295-1306. doi: 10.1016/j.jacc.2024.02.009.

  PMID: 38569758 BACKGROUND

MeSH Terms

Interventions

Acetazolamide; dapagliflozin

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Nouran Mo Anwar, Bachelor

CONTACT

01124119559; Nouran.Anwar@pharm.helwan.edu.eg

Mahmoud I Mostafa, PhD

CONTACT

01006605563; Mahmoud.ibrahim@pharma.helwan.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Clinical Pharmacy.Lecturer of Clinical Pharmacy, Faculty of Pharmacy, Helwan University, Cairo, Egypt.

Model Details: Prospective, open-label, randomized, two-armed parallel comparator study.

Study Record Dates

• First Submitted: June 29, 2024
• First Posted: August 2, 2024
• Study Start: August 24, 2024
• Primary Completion: August 1, 2025
• Study Completion: September 1, 2025
• Last Updated: August 5, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)