title: 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.
abstract: BACKGROUND
  Fluid overload refractory to loop diuretic therapy can complicate acute or chronic heart failure (HF) management. The Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) trial (Clinicaltrials.gov identifier NCT01647932) will test the hypothesis that blocking distal tubule sodium reabsorption with hydrochlorothiazide can antagonize the renal adaptation to chronic loop diuretic therapy and improve diuretic resistance.
  
  
  METHODS
  CLOROTIC is a randomized, placebo-controlled, double-blind, multicenter study. Three hundred and four patients with decompensated HF will be randomly assigned to receive hydrochlorothiazide or placebo in addition to a furosemide regimen. The main inclusion criteria are: age ≥18 years, history of chronic HF (irrespective of etiology and/or ejection fraction), admission for acute decompensation, and previous treatment with an oral loop diuretic for at least 1 month before randomization. The 2 coprimary endpoints are changes in body weight and changes in patient-reported dyspnea during hospital admission. Morbidity, mortality, and safety aspects will also be addressed.
  
  
  CONCLUSIONS
  CLOROTIC is the first large-scale trial to evaluate whether the addition of a thiazide diuretic (hydrochlorothiazide) to a loop diuretic (furosemide) is a safe and effective strategy for improving congestive symptoms resulting from HF. This trial will provide important information and will therefore have a major impact on treatment strategies and future trials in these patients.
authors.affiliation: Internal Medicine Service, Hospital d'Olot, Girona, Spain; Medical Science Department, University of Girona, Spain. Electronic address: jctv5153@comg.cat.
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Trullàs
authors.affiliation: Internal Medicine Service, Hospital Arnau de Vilanova, Lleida, Spain.
authors.forename: José Luís
authors.initials: JL
authors.lastname: Morales-Rull
authors.affiliation: Internal Medicine Service, Hospital de Getafe, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Casado
authors.affiliation: Departament de Salut, Generalitat de Catalunya, Servei d'Informació i Estudis, Barcelona, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Freitas Ramírez
authors.affiliation: Internal Medicine Service, Hospital Univ. Ramón y Cajal, Universidad de Alcalá, Madrid, Spain.
authors.forename: Luís
authors.initials: L
authors.lastname: Manzano
authors.affiliation: Internal Medicine Service, Hospital Universitari de Bellvitge-IDIBELL, Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Formiga
mesh_terms: D002908:Chronic Disease; D004232:Diuretics / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005665:Furosemide / Q000008:administration & dosage*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D004232:Diuretics; D006852:Hydrochlorothiazide; D005665:Furosemide
keywords: Heart failure; diuretics; furosemide; hydrochlorothiazide