Skip to main content
OpenTrials
Completed

NCT Number: NCT01647932

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Heart Failure Cardiovascular Diseases Heart Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Internal Medicine Service, Hospital d'Olot (Girona)

Olot, Girona, 17800, Spain

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Hydrochlorothiazide

Drug

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

Placebo

Drug

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 outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

Spanish Society of Internal Medicine

Other

Registry information

Official study 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).

Acronym: CLOROTIC

Important dates

Study start
2014
Primary completion
2019
Study completion
2019
First posted
Jul 24, 2012
Registry last updated
Oct 4, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.