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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06414759
Other study ID # CL3575
Secondary ID IHC00077
Status Not yet recruiting
Phase Phase 4
First received
Last updated
Start date May 22, 2024
Est. completion date March 30, 2025

Study information

Verified date May 2024
Source Cairo University
Contact Mohamed AN Abdelmoaty, B.Sc. Pharmaceutical Sciences
Phone +201146631157
Email mohamed.naguib@miuegypt.edu.eg
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study aims to compare two medications, acetazolamide and metolazone, along with loop diuretics, to see which one works better and is safer for patients with ADHF who have volume overload. By comparing these medications, we hope to learn which one can help these patients the most. This will help doctors choose the best treatment for patients with ADHF and volume overload.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 110
Est. completion date March 30, 2025
Est. primary completion date December 30, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria: - Male or female patients with ages = 18 years old, and less than 65 years old. - For both elective and emergency hospital admissions, patients with a clinical diagnosis of ADHF must exhibit at least one clinical sign indicative of volume overload. These signs may include edema (score 2 or higher), ascites confirmed through echography, or pleural effusion confirmed by chest X-ray or echography or rales on auscultation, or jugular venous pressure greater than10 mm Hg. Exclusion Criteria: - Patient diagnosed with acute kidney injury upon hospital admission based on the presence of any of the following criteria: an increase in SCr by at least 0.3 mg/dL within 48 hours, an increase in SCr to at least 2 times the baseline value, known or presumed to have occurred within the prior 7 days, and a urine volume less than 0.5 ml/kg/hour for a duration of 6 hours. - Patients with acute pulmonary edema caused by increased afterload and fluid redistribution to the lungs in the absence or with minimal fluid accumulation. - Anticipated exposure to nephrotoxic agents (such as contrast dye) during hospitalization. - Patients who exhibit anuria or are undergoing renal replacement therapy or ultrafiltration. - Patients with eGFR less than 30 mL/min/1.73m² at the time of screening. - Expected use of intravenous inotropes, vasopressors, or nitroprusside during the study. - Prior cardiac transplantation and/or utilization of a ventricular assist device. - Blood pressure below 90 mmHg or mean arterial pressure below 65 mmHg at the time of recruitment. - Patients who are pregnant or breastfeeding. - Administration of acetazolamide or metolazone within the one-month period preceding randomization. - The usage of any diuretic agent during the treatment phase is not specified in the study protocol, except for mineralocorticoid receptor antagonists.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Acetazolamide
Acetazolamide is a medication that belongs to the class of carbonic anhydrase inhibitors. It acts by reducing the reabsorption of sodium in the proximal tubules of the kidneys. When combined with loop diuretics, acetazolamide has the potential to enhance the effectiveness of diuretic therapy, thus aiding in the process of decongestion. It will be given 500mg orally, once daily.
Metolazone
Metolazone is a medication with properties like thiazide diuretics, prescribed for the management of congestive heart failure and hypertension. Its mechanism of action involves blocking the transport of sodium across the epithelium of renal tubules, predominantly in the distal tubules. It will be given 5mg orally, once daily.
IV Loop Diuretics
IV loop diuretic 2 times the outpatient oral (PO) daily dose, and oral loop diuretics will be stopped. In cases where the patient was not previously on oral diuretics, a starting dose of 40 mg of IV furosemide, IV bumetanide 1 mg or a bolus of 20 mg of IV torsemide can be utilized.

Locations

Country Name City State
Egypt National Heart Institute Giza GZ

Sponsors (2)

Lead Sponsor Collaborator
Cairo University National Heart Institute, Egypt

Country where clinical trial is conducted

Egypt, 

References & Publications (22)

Arrigo M, Jessup M, Mullens W, Reza N, Shah AM, Sliwa K, Mebazaa A. Acute heart failure. Nat Rev Dis Primers. 2020 Mar 5;6(1):16. doi: 10.1038/s41572-020-0151-7. — View Citation

Cox ZL, Hung R, Lenihan DJ, Testani JM. Diuretic Strategies for Loop Diuretic Resistance in Acute Heart Failure: The 3T Trial. JACC Heart Fail. 2020 Mar;8(3):157-168. doi: 10.1016/j.jchf.2019.09.012. Epub 2019 Dec 11. — View Citation

Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419. — View Citation

Hoorn EJ, Ellison DH. Diuretic Resistance. Am J Kidney Dis. 2017 Jan;69(1):136-142. doi: 10.1053/j.ajkd.2016.08.027. Epub 2016 Nov 1. — View Citation

Hsiao R, Greenberg B. Contemporary Treatment of Acute Heart Failure. Prog Cardiovasc Dis. 2016 Jan-Feb;58(4):367-78. doi: 10.1016/j.pcad.2015.12.005. Epub 2016 Jan 5. — View Citation

Inker LA, Eneanya ND, Coresh J, Tighiouart H, Wang D, Sang Y, Crews DC, Doria A, Estrella MM, Froissart M, Grams ME, Greene T, Grubb A, Gudnason V, Gutierrez OM, Kalil R, Karger AB, Mauer M, Navis G, Nelson RG, Poggio ED, Rodby R, Rossing P, Rule AD, Selvin E, Seegmiller JC, Shlipak MG, Torres VE, Yang W, Ballew SH, Couture SJ, Powe NR, Levey AS; Chronic Kidney Disease Epidemiology Collaboration. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. 2021 Nov 4;385(19):1737-1749. doi: 10.1056/NEJMoa2102953. Epub 2021 Sep 23. — View Citation

Januzzi JL, van Kimmenade R, Lainchbury J, Bayes-Genis A, Ordonez-Llanos J, Santalo-Bel M, Pinto YM, Richards M. NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the International Collaborative of NT-proBNP Study. Eur Heart J. 2006 Feb;27(3):330-7. doi: 10.1093/eurheartj/ehi631. Epub 2005 Nov 17. — View Citation

Jung B, Martinez M, Claessens YE, Darmon M, Klouche K, Lautrette A, Levraut J, Maury E, Oberlin M, Terzi N, Viglino D, Yordanov Y, Claret PG, Bige N; Societe de Reanimation de Langue Francaise (SRLF); Societe Francaise de Medecine d'Urgence (SFMU). Diagnosis and management of metabolic acidosis: guidelines from a French expert panel. Ann Intensive Care. 2019 Aug 15;9(1):92. doi: 10.1186/s13613-019-0563-2. — View Citation

Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179-84. doi: 10.1159/000339789. Epub 2012 Aug 7. No abstract available. — View Citation

Kim HN, Januzzi JL Jr. Natriuretic peptide testing in heart failure. Circulation. 2011 May 10;123(18):2015-9. doi: 10.1161/CIRCULATIONAHA.110.979500. No abstract available. — View Citation

Kurmani S, Squire I. Acute Heart Failure: Definition, Classification and Epidemiology. Curr Heart Fail Rep. 2017 Oct;14(5):385-392. doi: 10.1007/s11897-017-0351-y. — View Citation

McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available. Erratum In: Eur Heart J. 2021 Oct 14;: — View Citation

Mentz RJ, Kjeldsen K, Rossi GP, Voors AA, Cleland JG, Anker SD, Gheorghiade M, Fiuzat M, Rossignol P, Zannad F, Pitt B, O'Connor C, Felker GM. Decongestion in acute heart failure. Eur J Heart Fail. 2014 May;16(5):471-82. doi: 10.1002/ejhf.74. Epub 2014 Mar 5. — View Citation

Mullens W, Damman K, Harjola VP, Mebazaa A, Brunner-La Rocca HP, Martens P, Testani JM, Tang WHW, Orso F, Rossignol P, Metra M, Filippatos G, Seferovic PM, Ruschitzka F, Coats AJ. The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019 Feb;21(2):137-155. doi: 10.1002/ejhf.1369. Epub 2019 Jan 1. — View Citation

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. — View Citation

Ng TM, Konopka E, Hyderi AF, Hshieh S, Tsuji Y, Kim BJ, Han SY, Phan DH, Jeng AI, Lou M, Elkayam U. Comparison of bumetanide- and metolazone-based diuretic regimens to furosemide in acute heart failure. J Cardiovasc Pharmacol Ther. 2013 Jul;18(4):345-53. doi: 10.1177/1074248413482755. Epub 2013 Mar 27. — View Citation

Njoroge JN, Teerlink JR. Pathophysiology and Therapeutic Approaches to Acute Decompensated Heart Failure. Circ Res. 2021 May 14;128(10):1468-1486. doi: 10.1161/CIRCRESAHA.121.318186. Epub 2021 May 13. — View Citation

Rubio-Gracia J, Demissei BG, Ter Maaten JM, Cleland JG, O'Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Davison BA, Givertz MM, Bloomfield DM, Dittrich H, Damman K, Perez-Calvo JI, Voors AA. Prevalence, predictors and clinical outcome of residual congestion in acute decompensated heart failure. Int J Cardiol. 2018 May 1;258:185-191. doi: 10.1016/j.ijcard.2018.01.067. — View Citation

Sica DA. Metolazone and its role in edema management. Congest Heart Fail. 2003 Mar-Apr;9(2):100-5. doi: 10.1111/j.1527-5299.2003.01907.x. — View Citation

Suri SS, Pamboukian SV. Optimal diuretic strategies in heart failure. Ann Transl Med. 2021 Mar;9(6):517. doi: 10.21037/atm-20-4600. — View Citation

Verbrugge FH, Dupont M, Bertrand PB, Nijst P, Penders J, Dens J, Verhaert D, Vandervoort P, Tang WH, Mullens W. Determinants and impact of the natriuretic response to diuretic therapy in heart failure with reduced ejection fraction and volume overload. Acta Cardiol. 2015 Jun;70(3):265-73. doi: 10.1080/ac.70.3.3080630. — View Citation

Verbrugge FH, Martens P, Ameloot K, Haemels V, Penders J, Dupont M, Tang WHW, Droogne W, Mullens W. Acetazolamide to increase natriuresis in congestive heart failure at high risk for diuretic resistance. Eur J Heart Fail. 2019 Nov;21(11):1415-1422. doi: 10.1002/ejhf.1478. Epub 2019 May 9. — View Citation

* Note: There are 22 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Urine Output Total Urine output Volume 48 Hours
Secondary Diuretic Response Urine output/40 mg furosemide equivalent 48 Hours
Secondary Body Weight Change in Body Weight 48 Hours
Secondary Congestion Score Change in congestion score (Modified ADVOR Trial Congestion Score) 48 Hours
Secondary NT-proBNP/BNP Change in NT-Pro BNP/BNP levels On admission and before discharge (up to 2 Weeks)
Secondary Bicarbonate Level Change in bicarbonate level from baseline [ABG] 48 Hours
Secondary Serum Creatinine Change in serum creatinine (SCr) 48 Hours
Secondary eGFR Change in estimated glomerular filtration rate (eGFR) from baseline 48 Hours
Secondary Blood Pressure Change in systolic blood pressure (SBP) from baseline 48 Hours
Secondary Serum Potassium Change in serum potassium from baseline 48 Hours
Secondary Length of Hospital Stay Both general ward and CCU Up to 2 weeks
Secondary Mortality or HF Events All-cause mortality and heart failure readmission during 3 months of follow-up 3 Months
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