NCT01647932

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
232

participants targeted

Target at P50-P75 for phase_3 heart-failure

Timeline
Completed

Started Oct 2014

Longer than P75 for phase_3 heart-failure

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 28, 2012

Completed
26 days until next milestone

First Posted

Study publicly available on registry

July 24, 2012

Completed
2.2 years until next milestone

Study Start

First participant enrolled

October 1, 2014

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 15, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 15, 2019

Completed
Last Updated

October 4, 2022

Status Verified

September 1, 2022

Enrollment Period

5.2 years

First QC Date

June 28, 2012

Last Update Submit

September 30, 2022

Conditions

Heart Failure

Keywords

Heart FailureDiureticsDiuretic resistance

Outcome Measures

Primary Outcomes (2)

  • Changes in body weight

    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.

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

  • Patient-reported dyspnea

    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.

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

Secondary Outcomes (6)

  • Diuresis

    24-hour diuresis will be quantified every 24 hours (during hospitalisation) from the 1st day until the 4th day of hospitalisation.

  • Worsening renal function

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

  • Changes in electrolyte levels (sodium and potassium)

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

  • Metrics of diuretic response

    weight loss and net fluid loss per mg of furosemide

  • Mortality (all-cause and heart failure)

    Mortality (all-cause and heart failure) at 30 and 90days post-discharge

  • +1 more secondary outcomes

Study Arms (2)

Loop plus thiazide-type diuretic

ACTIVE COMPARATOR

Loop diuretic plus hydrochlorothiazide

Drug: hydrochlorothiazide

Loop diuretic plus placebo

PLACEBO COMPARATOR

Loop diuretic plus placebo

Drug: Placebo

Interventions

hydrochlorothiazideDRUG

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

Loop plus thiazide-type diuretic
PlaceboDRUG

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 diuretic plus placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • History of chronic heart failure
  • Admission for acute decompensated heart failure
  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Internal Medicine Service, Hospital d'Olot (Girona)

Olot, Girona, 17800, Spain

Location

Related Publications (9)

  • 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.

    PMID: 21029871BACKGROUND

  • ter Maaten JM, Valente MA, Damman K, Hillege HL, Navis G, Voors AA. Diuretic response in acute heart failure-pathophysiology, evaluation, and therapy. Nat Rev Cardiol. 2015 Mar;12(3):184-92. doi: 10.1038/nrcardio.2014.215. Epub 2015 Jan 6.

    PMID: 25560378BACKGROUND

  • Trullas JC, Morales-Rull JL, Casado J, Freitas Ramirez A, Manzano L, Formiga F; CLOROTIC investigators. Rationale and Design of the "Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) Trial:" A Double-Blind, Randomized, Placebo-Controlled Study to Determine the Effect of Combined Diuretic Therapy (Loop Diuretics With Thiazide-Type Diuretics) Among Patients With Decompensated Heart Failure. J Card Fail. 2016 Jul;22(7):529-36. doi: 10.1016/j.cardfail.2015.11.003. Epub 2015 Nov 11.

    PMID: 26576715BACKGROUND

  • Trullas JC, Morales-Rull JL, Formiga F. [Diuretic therapy in acute heart failure]. Med Clin (Barc). 2014 Mar;142 Suppl 1:36-41. doi: 10.1016/S0025-7753(14)70081-8. Spanish.

    PMID: 24930082BACKGROUND

  • Trullas JC, Casado J, Morales-Rull JL, Formiga F, Conde-Martel A, Quiros R, Epelde F, Gonzalez-Franco A, Manzano L, Montero-Perez-Barquero M. Prevalence and outcome of diuretic resistance in heart failure. Intern Emerg Med. 2019 Jun;14(4):529-537. doi: 10.1007/s11739-018-02019-7. Epub 2019 Jan 4.

    PMID: 30610440BACKGROUND

  • Conde-Martel A, Hernandez-Meneses M, Morales-Rull JL, Casado J, Carrera-Izquierdo M, Leon M, Sanchez-Marteles M, Davila-Ramos MF, Hernandez-Carballo C, Llacer P, Moreno-Garcia MC, Salamanca-Bautista P, Formiga F, Manzano L, Trullas JC. Hypokalemia During Decongestion With Loop Diuretics and Hydrochlorothiazide, a Post Hoc Analysis of the CLOROTIC Trial. Circ Heart Fail. 2025 Sep;18(9):e012914. doi: 10.1161/CIRCHEARTFAILURE.125.012914. Epub 2025 Jul 1.

    PMID: 40590131DERIVED

  • Conde-Martel A, Trullas JC, Morales-Rull JL, Casado J, Carrera-Izquierdo M, Sanchez-Marteles M, Llacer P, Salamanca-Bautista P, Manzano L, Formiga F. Sex differences in clinical characteristics and outcomes in the CLOROTIC (combining loop with thiazide diuretics for decompensated heart failure) trial. Rev Clin Esp (Barc). 2024 Feb;224(2):67-76. doi: 10.1016/j.rceng.2023.11.003. Epub 2024 Jan 11.

    PMID: 38215973DERIVED

  • Trullas JC, Morales-Rull JL, Casado J, Carrera-Izquierdo M, Sanchez-Marteles M, Conde-Martel A, Davila-Ramos MF, Llacer P, Salamanca-Bautista P, Chivite D, Jordana-Comajuncosa R, Villalonga M, Paez-Rubio MI, Manzano L, Formiga F. Combining loop and thiazide diuretics for acute heart failure across the estimated glomerular filtration rate spectrum: A post-hoc analysis of the CLOROTIC trial. Eur J Heart Fail. 2023 Oct;25(10):1784-1793. doi: 10.1002/ejhf.2988. Epub 2023 Aug 16.

    PMID: 37540036DERIVED

  • Trullas JC, Morales-Rull JL, Casado J, Carrera-Izquierdo M, Sanchez-Marteles M, Conde-Martel A, Davila-Ramos MF, Llacer P, Salamanca-Bautista P, Perez-Silvestre J, Plasin MA, Cerqueiro JM, Gil P, Formiga F, Manzano L; CLOROTIC trial investigators. Combining loop with thiazide diuretics for decompensated heart failure: the CLOROTIC trial. Eur Heart J. 2023 Feb 1;44(5):411-421. doi: 10.1093/eurheartj/ehac689.

    PMID: 36423214DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

ChlorothiazideBenzothiadiazinesSulfonamidesSulfonesSulfur CompoundsOrganic ChemicalsThiazidesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Joan Carles Trullas, MD, PhD

    Heart Failure Study Group, Spanish Society of Internal Medicine

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

June 28, 2012

First Posted

July 24, 2012

Study Start

October 1, 2014

Primary Completion

December 15, 2019

Study Completion

December 15, 2019

Last Updated

October 4, 2022

Record last verified: 2022-09

Locations

ES(1)