Safety and Efficacy of the Combination of Loop With Thiazide-type Diuretics in Patients With Decompensated Heart Failure

Summary

The purpose of this study is to determine whether a combined diuretic therapy (loop diuretics with thiazide-type diuretics) is more effective (in terms of improving fluid overload symptoms) among patients with decompensated heart failure in comparison with loop diuretic alone.

Timeline

Start

2014-10

Primary completion

2019-12-15

Completion

2019-12-15

Publications

• Background Jentzer JC, DeWald TA, Hernandez AF. Combination of loop diuretics with thiazide-type diuretics in heart failure. J Am Coll Cardiol. 2010 Nov 2;56(19):1527-34. doi: 10.1016/j.jacc.2010.06.034.
• Background ter Maaten JM, Valente MA, Damman K, Hillege HL, Navis G, Voors AA. Diuretic response in acute heart failure-pathophysiology, evaluation, and therapy. Nat Rev Cardiol. 2015 Mar;12(3):184-92. doi: 10.1038/nrcardio.2014.215. Epub 2015 Jan 6.
• Background Trullas JC, Morales-Rull JL, Casado J, Freitas Ramirez A, Manzano L, Formiga F; CLOROTIC investigators. Rationale and Design of the "Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) Trial:" A Double-Blind, Randomized, Placebo-Controlled Study to Determine the Effect of Combined Diuretic Therapy (Loop Diuretics With Thiazide-Type Diuretics) Among Patients With Decompensated Heart Failure. J Card Fail. 2016 Jul;22(7):529-36. doi: 10.1016/j.cardfail.2015.11.003. Epub 2015 Nov 11.
• Background Trullas JC, Morales-Rull JL, Formiga F. [Diuretic therapy in acute heart failure]. Med Clin (Barc). 2014 Mar;142 Suppl 1:36-41. doi: 10.1016/S0025-7753(14)70081-8. Spanish.
• Background Trullas JC, Casado J, Morales-Rull JL, Formiga F, Conde-Martel A, Quiros R, Epelde F, Gonzalez-Franco A, Manzano L, Montero-Perez-Barquero M. Prevalence and outcome of diuretic resistance in heart failure. Intern Emerg Med. 2019 Jun;14(4):529-537. doi: 10.1007/s11739-018-02019-7. Epub 2019 Jan 4.
• Garcia-Escriva D, Perez-Silvestre J, Nunez J, Casado J, Morales-Rull JL, Sanchez-Marteles M, Conde-Martel A, Llacer P, Salamanca-Bautista P, Plasin MA, Cerqueiro JM, Gil P, Manzano L, Formiga F, Trullas JC; CLOROTIC trial investigators. Serum chloride and the response to hydrochlorothiazide in patients with acute heart failure: a post-hoc analysis from the CLOROTIC trial. Rev Esp Cardiol (Engl Ed). 2026 May 18:S1885-5857(26)00104-0. doi: 10.1016/j.rec.2026.04.006. Online ahead of print. English, Spanish.
• McCallum W, Tighiouart H, Tuttle M, Oka T, Kaur T, Casado J, Morales-Rull JL, Formiga F, Manzano L, Testani JM, Sarnak MJ, Trullas JC. Acute declines in kidney function with thiazide plus loop diuretics vs loop diuretics alone in acute decompensated heart failure. Nephrol Dial Transplant. 2026 Mar 23:gfag070. doi: 10.1093/ndt/gfag070. Online ahead of print.
• Conde-Martel A, Hernandez-Meneses M, Morales-Rull JL, Casado J, Carrera-Izquierdo M, Leon M, Sanchez-Marteles M, Davila-Ramos MF, Hernandez-Carballo C, Llacer P, Moreno-Garcia MC, Salamanca-Bautista P, Formiga F, Manzano L, Trullas JC. Hypokalemia During Decongestion With Loop Diuretics and Hydrochlorothiazide, a Post Hoc Analysis of the CLOROTIC Trial. Circ Heart Fail. 2025 Sep;18(9):e012914. doi: 10.1161/CIRCHEARTFAILURE.125.012914. Epub 2025 Jul 1.
• Conde-Martel A, Trullas JC, Morales-Rull JL, Casado J, Carrera-Izquierdo M, Sanchez-Marteles M, Llacer P, Salamanca-Bautista P, Manzano L, Formiga F. Sex differences in clinical characteristics and outcomes in the CLOROTIC (combining loop with thiazide diuretics for decompensated heart failure) trial. Rev Clin Esp (Barc). 2024 Feb;224(2):67-76. doi: 10.1016/j.rceng.2023.11.003. Epub 2024 Jan 11.
• Trullas JC, Morales-Rull JL, Casado J, Carrera-Izquierdo M, Sanchez-Marteles M, Conde-Martel A, Davila-Ramos MF, Llacer P, Salamanca-Bautista P, Chivite D, Jordana-Comajuncosa R, Villalonga M, Paez-Rubio MI, Manzano L, Formiga F. Combining loop and thiazide diuretics for acute heart failure across the estimated glomerular filtration rate spectrum: A post-hoc analysis of the CLOROTIC trial. Eur J Heart Fail. 2023 Oct;25(10):1784-1793. doi: 10.1002/ejhf.2988. Epub 2023 Aug 16.
• Trullas JC, Morales-Rull JL, Casado J, Carrera-Izquierdo M, Sanchez-Marteles M, Conde-Martel A, Davila-Ramos MF, Llacer P, Salamanca-Bautista P, Perez-Silvestre J, Plasin MA, Cerqueiro JM, Gil P, Formiga F, Manzano L; CLOROTIC trial investigators. Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial. Eur Heart J. 2023 Feb 1;44(5):411-421. doi: 10.1093/eurheartj/ehac689.

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