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

This study is not yet open for participant recruitment.
Verified July 2012 by Spanish Society of Internal Medicine
Sponsor:
Information provided by (Responsible Party):
Joan Carles Trullas Vila, Spanish Society of Internal Medicine
ClinicalTrials.gov Identifier:
NCT01647932
First received: June 28, 2012
Last updated: July 19, 2012
Last verified: July 2012
History of Changes
  Purpose

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 Intervention Phase
Heart Failure
 Drug: hydrochlorothiazide
Drug: Placebo
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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).

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Spanish Society of Internal Medicine:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Diuresis [ Time Frame: 24-hour diuresis will be quantified every 24 hours (during hospitalisation) from the 1st day until the 4th day of hospitalisation. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

    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.


  • 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. ] [ Designated as safety issue: Yes ]

    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.


  • 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. ] [ Designated as safety issue: Yes ]

    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.



Estimated Enrollment: 400
Study Start Date: January 2013
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Loop plus thiazide-type diuretic
Loop diuretic plus hydrochlorothiazide
 Drug: hydrochlorothiazide
hydrochlorothiazide according to clearance of creatinine; >50ml/min 25mg QD, 20-50ml/min 50mg QD amd <20ml/min 100mg QD.
Placebo Comparator: Loop diuretic plus placebo
Loop diuretic plus placebo
 Drug: Placebo
Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01647932

Contacts
Contact: Joan Carles Trullas, MD, PhD 0034+667509933 jctv5153@comg.cat
Contact: Francesc Formiga, MD, PhD 0034+650964944 fformiga@bellvitgehospital.cat

Locations
Spain
Internal Medicine Service, Hospital Sant Jaume de Olot (Girona) Not yet recruiting
Olot, Girona, Spain, 17800
Contact: Joan Carles Trullas, MD, PhD     0034+66750933     jctv5153@comg.cat    
Principal Investigator: Joan Carles Trullas, MD, PhD            
Sponsors and Collaborators
Spanish Society of Internal Medicine
Investigators
Principal Investigator: Joan Carles Trullas, MD, PhD Heart Failure Study Group, Spanish Society of Internal Medicine
  More Information

Publications:

Responsible Party: Joan Carles Trullas Vila, Principal Investigator, Spanish Society of Internal Medicine
ClinicalTrials.gov Identifier: NCT01647932     History of Changes
Other Study ID Numbers: SEMI-IC-CLOR
Study First Received: June 28, 2012
Last Updated: July 19, 2012
Health Authority: Spain: Spanish Agency of Medicines
Spain: Ethics Committee

Keywords provided by Spanish Society of Internal Medicine:
Heart Failure

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Diuretics
Hydrochlorothiazide
Sodium Potassium Chloride Symporter Inhibitors
Natriuretic Agents
Physiological Effects of Drugs
 Pharmacologic Actions
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2013