Trial | NCT01647932  Report issue

Title

Safety and Efficacy of the Combination of Loop With Thiazide-type Diuretics in Patients With Decompensated Heart Failure
Safety and Efficacy of the Combination of Loop Diuretics With Thiazide-type Diuretics in Patients With Decompensated Heart Failure: a Double-blind, Randomized, Placebo-controlled Trial (CLOROTIC Trial).

  • Phase

    Phase 4

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    232
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.
Volume overload is an important clinical target in heart failure management, typically addressed using loop diuretics. An important and challenging subset of heart failure patients exhibit fluid overload despite significant doses of loop diuretics. One approach to overcome loop diuretic resistance is the addition of a thiazide-type diuretic to produce diuretic synergy via "sequential nephron blockade," first described more than 40 years ago. Although potentially able to induce diuresis in patients otherwise resistant to high doses of loop diuretics, this strategy has not been subjected to large-scale clinical trials to establish safety and clinical efficacy. Combination diuretic therapy using any of several thiazide-type diuretics can more than double daily urine sodium excretion to induce weight loss and edema resolution. To our knowledge there are no clinical trials designed to prove the efficacy and safety of combined diuretic therapy (a commonly used therapy) among patients with decompensated heart failure.
Study Started
Oct 31
2014
Primary Completion
Dec 15
2019
Study Completion
Dec 15
2019
Last Update
Oct 04
2022

Drug hydrochlorothiazide

hydrochlorothiazide according to clearance of creatinine; >50ml/min 25mg daily, 20-50ml/min 50mg daily amd <20ml/min 100mg daily.

Drug Placebo

Placebo according to clearance of creatinine; >50ml/min 1/2 pill daily, 20-50ml/min 1 pill daily amd <20ml/min 2 pills daily.

Loop plus thiazide-type diuretic Active Comparator

Loop diuretic plus hydrochlorothiazide

Loop diuretic plus placebo Placebo Comparator

Loop diuretic plus placebo

Criteria 

Inclusion Criteria:

History of chronic heart failure
Admission for acute decompensated heart failure
There is no prespecified inclusion criterion with respect to heart failure etiology and/or ejection fraction
Receipt of an oral loop diuretic for at least 1 month before hospitalization, at a dose between 80 mg and 240 mg daily in the case of furosemide and an equivalent dose in the case of a different loop diuretic (20 mg of torasemide or 1 mg of bumetanide was considered to be equivalent to 40 mg of furosemide)

Exclusion Criteria:

Other etiologies of fluid overload different from heart failure
Hyponatremia: any symptomatic sodium value or a sodium level below 125mmol/l
Unstable patients: acute coronary syndrome, cardiogenic shock or ICU admission.
Patients requiring inotropic agents or renal replacement therapies
Life expectancy < 6 months
Prior treatment with thiazide-type diuretics
Aldosterone antagonists are permitted if the patient had been taking them on a long-term basis (at least 30 days before randomisation)
Pregnancy or breastfeeding period
Active alcoholism and/or other substance abuse
No Results Posted