Clinical trial NCT00409942: Effect of a New Formulation of Torasemide (Prolonged Release)on Myocardial Fibrosis in Patients With Heart Failure.
Official title: Prospective, Randomised, Open, Blinded-endpoint Study of Torasemide Prolonged Release vs Furosemide to Evaluate the Efficacy on Myocardial Fibrosis in Patients With Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Congestive Heart Failure
Keywords: Chronic heart failure
Torasemide prolonged release
Myocardial fibrosis
Loop diuretics
Peptide of procollagen type 1
Lead sponsor: Ferrer Internacional S.A.
Sponsor class: INDUSTRY
First posted: 2006-12-12
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Torasemide is a loop diuretic (pyridine-sulfonylurea)with a wide experience in the treatment of oedema associated to heart failure, kidney or liver disease and either in the treatment of arterial hypertension (alone or combined with other anti-hypertensive drugs). It has been developed a new formulation of Torasemide (Torasemide prolonged release).

The aim of this trial is to study the effects of Torasemide prolonged released in comparison with furosemide, in the reduction of myocardial fibrosis in patients with chronic heart failure (Class II-IV of the New York Heart Association Classification.


Eligibility criteria: Inclusion Criteria:

* Aged over 18
* Patients with chronic heart failure class II-IV (NYHA)due to arterial hypertension
* Patients clinically stable who required diuretic treatment
* Patients with left ventricular hypertrophy diagnosed by echocardiogram
* Patients without ischaemic cardiopathy or non recent disease
* Signed Informed Consent

Exclusion Criteria:

* Heart Failure due to aortic stenosis or hypertrophic myocardiopathy
* Recent coronary syndrome (less than 3 months)
* Recent myocardial infarction (less than 6 months)
* Unstable angor pectoris
* Severe cardiac arrhythmia
* Pregnancy or breastfeeding
* Aldosterone antagonists (last 6 months)
* Current loop diuretic treatment over study doses (torasemide \> 10mg/day furosemide \> 40 mg/day)
* known hypersensitivity to study drugs
* Liver disease (SGPT or AST \> twice upper normal limt)
* Renal impairment (Serum creatinine \> 2,5mg/dl)
* Insulin-dependent diabetes
* Patient included in another simultaneous study
* Lactose intolerance
* Lithium Concomitant treatment
* Chronic treatment with NSAIDs
* Concomitant treatment with aminoglycoside antibiotics,etacrynic acid

Primary outcomes:
measure: Myocardial fibrosis reduction:measure of Serum carboxy-terminal peptide of procollagen type 1.
timeFrame: 8 months
Secondary outcomes:
measure: Clinical improvement (New York Heart Association classification, signs and symptoms of heart failure)
timeFrame: 8 months
measure: Cardiovascular events
timeFrame: 8 months
measure: NT-proBNP (Brain Natriuretic Peptide)
timeFrame: 8 months
measure: Hospitalizations, home care due to cardiovascular causes related to heart failure
timeFrame: 8 months
measure: Safety and tolerability
timeFrame: 8 months
measure: Quality of Life (Minnesota Test)
timeFrame: 8 months
Other outcomes:
Locations:
city: Oviedo
country: Spain
facility: Central Hospital
state: Asturias
city: Canet de Mar
country: Spain
facility: Canet de Mar, Primary Care Centre
state: Barcelona
city: Centellas
country: Spain
facility: Centelles - Primar Care Centre
state: Barcelona
city: Mataró
country: Spain
facility: El Maresme - Primary Care Centre
state: Barcelona
city: Vic
country: Spain
facility: Remei, Primary care centre
state: Barcelona
city: Begonte
country: Spain
facility: Begonte - Primary Care Centre
state: Lugo
city: Málaga
country: Spain
facility: Clinico Universitario Virgen de la Victoria
state: Malaga
city: Donostia
country: Spain
facility: Donostia Hospital
state: San Sebastián
city: Alcover
country: Spain
facility: Alcover - primary care centre
state: Tarragona
city: Barcelona
country: Spain
facility: Clinc Hospital
city: Barcelona
country: Spain
facility: Germans Trias i Pujol Hospital
city: Barcelona
country: Spain
facility: H. del Mar
city: Barcelona
country: Spain
facility: Valle Hebrón Hospital
city: Córdoba
country: Spain
facility: Reina Sofia Hospital
city: Girona
country: Spain
facility: Josep Trueta Hospital
city: Huesca
country: Spain
facility: San Jorge Hospital
city: La Coruña
country: Spain
facility: Complejo Hospitalario Juan Canalejo
city: Madrid
country: Spain
facility: Gregorio Marañón Hospital
city: Murcia
country: Spain
facility: Virgen de la Arrixaca
city: Salamanca
country: Spain
facility: Clinico Universitario Hospital
city: Santiago de Compostela
country: Spain
facility: Clinico Universitario de Santiago
city: Valencia
country: Spain
facility: General Hospital
city: Zaragoza
country: Spain
facility: Clinico Universitario
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Antonio Coca, MD, PhD
role: STUDY_CHAIR
affiliation: Hospital Reina Sofia - Córdoba
name: Manuel Anguita, MD, PhD
role: STUDY_CHAIR
affiliation: Hospital Clinico - Málaga
name: Eduardo De Teresa, MD, PhD
role: STUDY_CHAIR
affiliation: Hospital Juan Canalejo - Coruña
name: Alfonso Castro Beiras, MD, PhD
role: STUDY_CHAIR
affiliation: Centro Investigación Médica Aplicada (CIMA) - Pamplona (Navarra)
name: Javier Díez
role: STUDY_DIRECTOR
References:
citation: Querejeta R, Lopez B, Gonzalez A, Sanchez E, Larman M, Martinez Ubago JL, Diez J. Increased collagen type I synthesis in patients with heart failure of hypertensive origin: relation to myocardial fibrosis. Circulation. 2004 Sep 7;110(10):1263-8. doi: 10.1161/01.CIR.0000140973.60992.9A. Epub 2004 Aug 16.
citation: Gonzalez A, Lopez B, Diez J. New directions in the assessment and treatment of hypertensive heart disease. Curr Opin Nephrol Hypertens. 2005 Sep;14(5):428-34. doi: 10.1097/01.mnh.0000174143.30045.bd.
citation: Lopez B, Querejeta R, Gonzalez A, Sanchez E, Larman M, Diez J. Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure. J Am Coll Cardiol. 2004 Jun 2;43(11):2028-35. doi: 10.1016/j.jacc.2003.12.052.
citation: Lopez B, Gonzalez A, Querejeta R, Diez J. The use of collagen-derived serum peptides for the clinical assessment of hypertensive heart disease. J Hypertens. 2005 Aug;23(8):1445-51. doi: 10.1097/01.hjh.0000173780.67308.f1.
citation: Lopez B, Gonzalez A, Beaumont J, Querejeta R, Larman M, Diez J. Identification of a potential cardiac antifibrotic mechanism of torasemide in patients with chronic heart failure. J Am Coll Cardiol. 2007 Aug 28;50(9):859-67. doi: 10.1016/j.jacc.2007.04.080. Epub 2007 Aug 13.
citation: TORAFIC Investigators Group. Effects of prolonged-release torasemide versus furosemide on myocardial fibrosis in hypertensive patients with chronic heart failure: a randomized, blinded-end point, active-controlled study. Clin Ther. 2011 Sep;33(9):1204-1213.e3. doi: 10.1016/j.clinthera.2011.08.006. Epub 2011 Sep 8.
citation: Diez J, Coca A, de Teresa E, Anguita M, Castro-Beiras A, Conthe P, Cobo E, Fernandez E; TORAFIC Investigators Group. TORAFIC study protocol: torasemide prolonged release versus furosemide in patients with chronic heart failure. Expert Rev Cardiovasc Ther. 2009 Aug;7(8):897-904. doi: 10.1586/erc.09.74.