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Trial record 1 of 1 for:    clorotic
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Safety and Efficacy of the Combination of Loop With Thiazide-type Diuretics in Patients With Decompensated Heart Failure (CLOROTIC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01647932
Recruitment Status : Completed
First Posted : July 24, 2012
Last Update Posted : December 17, 2019
Sponsor:
Information provided by (Responsible Party):
Joan Carles Trullas Vila, Spanish Society of Internal Medicine

Brief 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.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: hydrochlorothiazide Drug: Placebo Phase 4

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 234 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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).
Study Start Date : October 2014
Actual Primary Completion Date : December 15, 2019
Actual Study Completion Date : December 15, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Active Comparator: Loop plus thiazide-type diuretic
Loop diuretic plus hydrochlorothiazide
Drug: hydrochlorothiazide
hydrochlorothiazide according to clearance of creatinine; >50ml/min 25mg daily, 20-50ml/min 50mg daily amd <20ml/min 100mg daily.

Placebo Comparator: Loop diuretic plus placebo
Loop diuretic plus placebo
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.




Primary Outcome Measures :
  1. Changes in body weight [ Time Frame: Bodyweight will be measured every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge. ]

    Bodyweight will be measured every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.

    Changes in body weight measurements: the mean of weight lost every 24 hours and the total weight lost from baseline to the 5th day of hospitalisation.

    Participants will be followed for the duration of hospital stay, an expected average of 9 days.


  2. Patient-reported dyspnea [ Time Frame: Patient-reported dyspnea is assessed every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge. ]

    Patient-reported dyspnea is assessed every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.

    Patient-reported dyspnea is assessed with the use of a visual-analogue scale (VAS) and the Linker 7 point scale.

    Changes in patient-reported dyspnea: changes in the dyspnea scales from baseline to the 5th day of hospitalisation.



Secondary Outcome Measures :
  1. Diuresis [ Time Frame: 24-hour diuresis will be quantified every 24 hours (during hospitalisation) from the 1st day until the 4th day of hospitalisation. ]
  2. Worsening renal function [ Time Frame: Renal function will be determined every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge. ]

    Renal function will be determined every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.

    Renal function is assessed with the serum creatinine level. Worsening renal function is defined as an increase in the serum creatinine level of more than 0.3 mg/dl at any time during hospitalisation Participants will be followed for the duration of hospital stay, an expected average of 9 days.


  3. Changes in electrolyte levels (sodium and potassium) [ Time Frame: Electrolyte levels (sodium and potassium) will be determined every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge. ]

    Electrolyte levels (sodium and potassium) will be determined every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.

    Electrolyte levels are assessed with the serum sodium and potassium levels. Participants will be followed for the duration of hospital stay, an expected average of 9 days.


  4. Metrics of diuretic response [ Time Frame: weight loss and net fluid loss per mg of furosemide ]
    weight loss and net fluid loss per mg of furosemide

  5. Mortality (all-cause and heart failure) [ Time Frame: Mortality (all-cause and heart failure) at 30 and 90days post-discharge ]
    Mortality (all-cause and heart failure) at 30 and 90days post-discharge

  6. Rehospitalization (all-cause and heart failure) [ Time Frame: Rehospitalization (all-cause and heart failure) at 30 and 90days post-discharge ]
    Rehospitalization (all-cause and heart failure) at 30 and 90days post-discharge



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01647932


Locations
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Spain
Internal Medicine Service, Hospital d'Olot (Girona)
Olot, Girona, Spain, 17800
Sponsors and Collaborators
Spanish Society of Internal Medicine
Investigators
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Principal Investigator: Joan Carles Trullas, MD, PhD Heart Failure Study Group, Spanish Society of Internal Medicine

Publications:

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Responsible Party: Joan Carles Trullas Vila, Principal Investigator, Spanish Society of Internal Medicine
ClinicalTrials.gov Identifier: NCT01647932    
Other Study ID Numbers: SEMI-IC-CLOR
First Posted: July 24, 2012    Key Record Dates
Last Update Posted: December 17, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joan Carles Trullas Vila, Spanish Society of Internal Medicine:
Heart Failure
Diuretics
Diuretic resistance
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Hydrochlorothiazide
Diuretics
Sodium Potassium Chloride Symporter Inhibitors
Antihypertensive Agents
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action