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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 currently recruiting participants. (see Contacts and Locations)
Verified October 2014 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: October 28, 2014
Last verified: October 2014

June 28, 2012
October 28, 2014
October 2014
October 2015   (final data collection date for primary outcome measure)
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.

Same as current
Complete list of historical versions of study NCT01647932 on ClinicalTrials.gov Archive Site
  • 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.

Same as current
Not Provided
Not Provided
 
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).

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Heart Failure
  • Drug: hydrochlorothiazide
    hydrochlorothiazide according to clearance of creatinine; >50ml/min 25mg QD, 20-50ml/min 50mg QD amd <20ml/min 100mg QD.
  • Drug: Placebo
    Placebo
  • Active Comparator: Loop plus thiazide-type diuretic
    Loop diuretic plus hydrochlorothiazide
    Intervention: Drug: hydrochlorothiazide
  • Placebo Comparator: Loop diuretic plus placebo
    Loop diuretic plus placebo
    Intervention: Drug: Placebo
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. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
400
January 2016
October 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Joan Carles Trullas, MD, PhD 0034+667509933 jctv5153@comg.cat
Contact: Francesc Formiga, MD, PhD 0034+650964944 fformiga@bellvitgehospital.cat
Spain
 
NCT01647932
SEMI-IC-CLOR
No
Joan Carles Trullas Vila, Spanish Society of Internal Medicine
Spanish Society of Internal Medicine
Not Provided
Principal Investigator: Joan Carles Trullas, MD, PhD Heart Failure Study Group, Spanish Society of Internal Medicine
Spanish Society of Internal Medicine
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP