Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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:
Participants will:
A. Study design
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acetazolamide + Standard Care | Active Comparator | Participants in this arm will receive:
|
|
| Dapagliflozin + Standard Care | Active Comparator | Participants in this arm will receive:
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Acetazolamide | Drug | Patients will receive acetazolamide 500 mg once daily for 3 days as add on therapy to IV loop diuretics |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Successful decongestion | 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nouran Mo Anwar, Bachelor | Contact | 01124119559 | Nouran.Anwar@pharm.helwan.edu.eg | |
| Mahmoud I Mostafa, PhD | Contact | 01006605563 | Mahmoud.ibrahim@pharma.helwan.edu.eg |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Critical Care Medicine Department - Cairo University Hospitals. | Recruiting | Cairo | Egypt |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30238574 | Background | 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. | |
| 36027559 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000086 | Acetazolamide |
| C529054 | dapagliflozin |
| ID | Term |
|---|---|
| D013830 | Thiadiazoles |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
Not provided
Not provided
Prospective, open-label, randomized, two-armed parallel comparator study.
Not provided
Not provided
Not provided
Not provided
| Dapagliflozin 10mg | Drug | patient will receive oral dapagliflozin 10 mg once daily for 3 days as add on therapy to IV loop diuretics |
|
|
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 | Proportion of patients who die from any cause within 30 days of randomization | Up to 30 days |
| Cumulative dose of intravenous loop diuretics | Total milligrams of intravenous furosemide or equivalent dose of other loop diuretics administered | 5 days |
| Incidence of treatment-related metabolic acidosis | Proportion of patients developing metabolic acidosis requiring sodium bicarbonate (NaHCO3) supplementation | 5 days |
| percent of worsening renal failure (WRF) | 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 |
| 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. |
| 37207453 | 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. |
| 37213994 | 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. |
| 38202295 | 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. |
| 37415505 | 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. |
| 38416359 | 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. |
| 38569758 | 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. |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |