Ignite Creation Date:
2025-12-24 @ 9:45 PM
Ignite Modification Date:
2026-02-21 @ 11:36 PM
Study NCT ID:
NCT01647932
Status:
COMPLETED
Last Update Posted:
2022-10-04
First Post:
2012-06-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety and Efficacy of the Combination of Loop With Thiazide-type Diuretics in Patients With Decompensated Heart Failure
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D006333', 'term': 'Heart Failure'}], 'ancestors': [{'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D006852', 'term': 'Hydrochlorothiazide'}], 'ancestors': [{'id': 'D002740', 'term': 'Chlorothiazide'}, {'id': 'D001581', 'term': 'Benzothiadiazines'}, {'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D049971', 'term': 'Thiazides'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 232}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-10'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-09', 'completionDateStruct': {'date': '2019-12-15', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-09-30', 'studyFirstSubmitDate': '2012-06-28', 'studyFirstSubmitQcDate': '2012-07-19', 'lastUpdatePostDateStruct': {'date': '2022-10-04', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2012-07-24', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2019-12-15', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Changes in body weight', 'timeFrame': 'Bodyweight will be measured every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.', 'description': 'Bodyweight will be measured every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.\n\nChanges 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.\n\nParticipants will be followed for the duration of hospital stay, an expected average of 9 days.'}, {'measure': 'Patient-reported dyspnea', 'timeFrame': 'Patient-reported dyspnea is assessed every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.', 'description': 'Patient-reported dyspnea is assessed every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.\n\nPatient-reported dyspnea is assessed with the use of a visual-analogue scale (VAS) and the Linker 7 point scale.\n\nChanges in patient-reported dyspnea: changes in the dyspnea scales from baseline to the 5th day of hospitalisation.'}], 'secondaryOutcomes': [{'measure': 'Diuresis', 'timeFrame': '24-hour diuresis will be quantified every 24 hours (during hospitalisation) from the 1st day until the 4th day of hospitalisation.'}, {'measure': 'Worsening renal function', 'timeFrame': 'Renal function will be determined every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.', 'description': 'Renal function will be determined every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.\n\nRenal 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.'}, {'measure': 'Changes in electrolyte levels (sodium and potassium)', 'timeFrame': 'Electrolyte levels (sodium and potassium) will be determined every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.', 'description': 'Electrolyte levels (sodium and potassium) will be determined every 24 hours (during hospitalisation) from the date of inclusion / randomisation until the date of discharge.\n\nElectrolyte 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.'}, {'measure': 'Metrics of diuretic response', 'timeFrame': 'weight loss and net fluid loss per mg of furosemide', 'description': 'weight loss and net fluid loss per mg of furosemide'}, {'measure': 'Mortality (all-cause and heart failure)', 'timeFrame': 'Mortality (all-cause and heart failure) at 30 and 90days post-discharge', 'description': 'Mortality (all-cause and heart failure) at 30 and 90days post-discharge'}, {'measure': 'Rehospitalization (all-cause and heart failure)', 'timeFrame': 'Rehospitalization (all-cause and heart failure) at 30 and 90days post-discharge', 'description': 'Rehospitalization (all-cause and heart failure) at 30 and 90days post-discharge'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Heart Failure', 'Diuretics', 'Diuretic resistance'], 'conditions': ['Heart Failure']}, 'referencesModule': {'references': [{'pmid': '21029871', 'type': 'BACKGROUND', 'citation': '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': '25560378', 'type': 'BACKGROUND', 'citation': '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': '26576715', 'type': 'BACKGROUND', 'citation': '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': '24930082', 'type': 'BACKGROUND', 'citation': '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': '30610440', 'type': 'BACKGROUND', 'citation': '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': '40590131', 'type': 'DERIVED', 'citation': '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': '38215973', 'type': 'DERIVED', 'citation': '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': '37540036', 'type': 'DERIVED', 'citation': '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': '36423214', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* History of chronic heart failure\n* Admission for acute decompensated heart failure\n* There is no prespecified inclusion criterion with respect to heart failure etiology and/or ejection fraction\n* 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)\n\nExclusion Criteria:\n\n* Other etiologies of fluid overload different from heart failure\n* Hyponatremia: any symptomatic sodium value or a sodium level below 125mmol/l\n* Unstable patients: acute coronary syndrome, cardiogenic shock or ICU admission.\n* Patients requiring inotropic agents or renal replacement therapies\n* Life expectancy \\< 6 months\n* Prior treatment with thiazide-type diuretics\n* Aldosterone antagonists are permitted if the patient had been taking them on a long-term basis (at least 30 days before randomisation)\n* Pregnancy or breastfeeding period\n* Active alcoholism and/or other substance abuse'}, 'identificationModule': {'nctId': 'NCT01647932', 'acronym': 'CLOROTIC', 'briefTitle': 'Safety and Efficacy of the Combination of Loop With Thiazide-type Diuretics in Patients With Decompensated Heart Failure', 'organization': {'class': 'OTHER', 'fullName': 'Spanish Society of Internal Medicine'}, 'officialTitle': '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).', 'orgStudyIdInfo': {'id': 'SEMI-IC-CLOR'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Loop plus thiazide-type diuretic', 'description': 'Loop diuretic plus hydrochlorothiazide', 'interventionNames': ['Drug: hydrochlorothiazide']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Loop diuretic plus placebo', 'description': 'Loop diuretic plus placebo', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'hydrochlorothiazide', 'type': 'DRUG', 'description': 'hydrochlorothiazide according to clearance of creatinine; \\>50ml/min 25mg daily, 20-50ml/min 50mg daily amd \\<20ml/min 100mg daily.', 'armGroupLabels': ['Loop plus thiazide-type diuretic']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo according to clearance of creatinine; \\>50ml/min 1/2 pill daily, 20-50ml/min 1 pill daily amd \\<20ml/min 2 pills daily.', 'armGroupLabels': ['Loop diuretic plus placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '17800', 'city': 'Olot', 'state': 'Girona', 'country': 'Spain', 'facility': "Internal Medicine Service, Hospital d'Olot (Girona)", 'geoPoint': {'lat': 42.18096, 'lon': 2.49012}}], 'overallOfficials': [{'name': 'Joan Carles Trullas, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Heart Failure Study Group, Spanish Society of Internal Medicine'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Spanish Society of Internal Medicine', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Joan Carles Trullas Vila', 'investigatorAffiliation': 'Spanish Society of Internal Medicine'}}}}