Effect of a New Formulation of Torasemide (Prolonged Release)on Myocardial Fibrosis in Patients With Heart Failure.

Congestive Heart Failure Clinical Trial

— TORAFIC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00409942
• Other study ID #: N/GF-TORAFIC-06
• Secondary ID: EudraCT number 2
• Status: Completed
• Phase: Phase 4
• First received: December 11, 2006
• Last updated: July 14, 2009
• Start date: March 2007
• Est. completion date: June 2009

Study information

• Verified date: June 2009
• Source: Ferrer Internacional S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure

Intervention

Drug:
• Torasemide Prolonged Release
Torasemide Prolonged release 10mg/day up to 40mg/day, treatment duration:8 months
• Furosemide
Furosemide 40mg/day up to 160mg/day, Treatment duration:8 months

Locations

Country	Name	City	State
Spain	Alcover - primary care centre	Alcover	Tarragona
Spain	Clinc Hospital	Barcelona
Spain	Germans Trias i Pujol Hospital	Barcelona
Spain	H. del Mar	Barcelona
Spain	Valle Hebrón Hospital	Barcelona
Spain	Begonte - Primary Care Centre	Begonte	Lugo
Spain	Canet de Mar, Primary Care Centre	Canet de Mar	Barcelona
Spain	Centelles - Primar Care Centre	Centellas	Barcelona
Spain	Reina Sofia Hospital	Córdoba
Spain	Donostia Hospital	Donostia	San Sebastián
Spain	Josep Trueta Hospital	Girona
Spain	San Jorge Hospital	Huesca
Spain	Complejo Hospitalario Juan Canalejo	La Coruña
Spain	Gregorio Marañón Hospital	Madrid
Spain	Clinico Universitario Virgen de la Victoria	Málaga	Malaga
Spain	El Maresme - Primary Care Centre	Mataró	Barcelona
Spain	Virgen de la Arrixaca	Murcia
Spain	Central Hospital	Oviedo	Asturias
Spain	Clinico Universitario Hospital	Salamanca
Spain	Clinico Universitario de Santiago	Santiago de Compostela
Spain	General Hospital	Valencia
Spain	Remei, Primary care centre	Vic	Barcelona
Spain	Clinico Universitario	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Ferrer Internacional S.A.

Country where clinical trial is conducted

Spain, 

References & Publications (5)

González A, López B, Díez J. New directions in the assessment and treatment of hypertensive heart disease. Curr Opin Nephrol Hypertens. 2005 Sep;14(5):428-34. Review. — View Citation

López B, González A, Beaumont J, Querejeta R, Larman M, Díez 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. Epub 2007 Aug 13. — View Citation

López B, González A, Querejeta R, Díez J. The use of collagen-derived serum peptides for the clinical assessment of hypertensive heart disease. J Hypertens. 2005 Aug;23(8):1445-51. Review. — View Citation

López B, Querejeta R, González A, Sánchez E, Larman M, Díez 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. — View Citation

Querejeta R, López B, González A, Sánchez E, Larman M, Martínez Ubago JL, Díez 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. Epub 2004 Aug 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial fibrosis reduction:measure of Serum carboxy-terminal peptide of procollagen type 1.		8 months	No
Secondary	Clinical improvement (New York Heart Association classification, signs and symptoms of heart failure)		8 months	No
Secondary	Cardiovascular events		8 months	Yes
Secondary	NT-proBNP (Brain Natriuretic Peptide)		8 months	No
Secondary	Hospitalizations, home care due to cardiovascular causes related to heart failure		8 months	Yes
Secondary	Safety and tolerability		8 months	Yes
Secondary	Quality of Life (Minnesota Test)		8 months	No