Clinical trial NCT01942109: The Impact of TORasemide oN hemodynAmic and Neurohormonal Stress, and carDiac remOdeling in Heart Failure
Official title: The Impact of TORasemide oN hemodynAmic and Neurohormonal Stress, and carDiac remOdeling in Heart Failure - Prospective, Randomized, Open, Blinded Endpoint Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Heart Failure
Keywords: heart failure
diuretics
furosemide
torasemide
Lead sponsor: Medical University of Warsaw
Sponsor class: OTHER
First posted: 2013-09-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the study is to compare the effects of torasemide and furosemide on clinical and biochemical parameters of hemodynamic and neurohormonal compensation and myocardial remodeling in patients with chronic heart failure with indications for use of loop diuretics.

The study protocol 100 patients with heart failure NYHA (New York Heart Association) II-IV (stable or exacerbation aligned cardiopulmonary at the time of enrollment, with a fixed-dose loop diuretics\]) treated with optimal medical therapy as clinically indicated for use loop diuretics. Patients will be randomized to treatment with furosemide and torasemide (randomization 1 : 1). After randomization, furosemide will continue in its current fixed-dose or will be replaced by equipotential dose of torasemide (4:1). The minimal follow-up of patients in the study will be at least six months.

Detailed description: According to current guidelines, angiotensin converting enzyme inhibitors and beta-adrenolytics are the first-line treatment agents in patients with heart failure. In case of fluid retention, diuretics, as a part of symptomatic treatment, should be administered. In practice, the most common diuretic used in patients with heart failure is loop diuretic - furosemide. What is important, furosemide has no effect on patients' outcomes. Some studies showed unfavourable influence of this drug on rennin-angiotensin-aldosterone system.

Alternative loop diuretic, which may be administered in patients with heart failure is torasemide. Its longer elimination half-life time, similar diuretic effects, lower influence on electrolyte disorders and additional pleiotropic effects could make torasemide more beneficial than furosemide.

Accordingly, only direct comparison of furosemide and torasemide could present similarities and differences of these two agents.

The hypothesis of this study is that torasemide may present more favourable effects on some clinical parameters in patients with heart failure, than furosemide (e.g. clinical symptoms, biochemical parameters, activity of rennin-angiotensin-aldosterone system, side effects).

Eligibility criteria: Inclusion Criteria:

* heart failure NYHA II-IV
* previous treatment with diuretics
* age\>18 years

Exclusion Criteria:

* uncontrolled hypertension
* uncontrolled diabetes
* creatinine \> 2,5 mg/dl
* potassium \> 6 mg/dl
* acute coronary syndrome
* hypertrophic cardiomyopathy

Primary outcomes:
measure: The influence of therapy on cardiovascular events associated with heart failure (deaths, hospitalisations)
timeFrame: up to 12 months
Secondary outcomes:
measure: The change of dosing of diuretic due to worsening of condition of patient.
timeFrame: up to 12 months
measure: The change of NYHA (New York Heart Association) class - worsening or improvement
timeFrame: up to 12 months
Other outcomes:
measure: The measurement of fluid retention with ZOE Fluid Status Monitor
timeFrame: up to 12 months
measure: ≥30% or ≥200 pg/ml increase of NTproBNP (N-terminal pro B type natriuretic peptide) level compared with baseline value
timeFrame: up to 12 months
measure: The change between baseline and final levels of serum biomarkers
timeFrame: up to 12 months
measure: The assessment of quality of life
timeFrame: up to 12 months
Locations:
city: Warsaw
country: Poland
facility: 3rd Clinic of Internal Medicine and Cardiology of Medcial University of Warsaw
state: Mazowieckie
city: Warsaw
country: Poland
facility: 1st Department of Cariology of Medcial University of Warsaw
state: Mazowieckie
Study officials:
affiliation: 1st Department of Cardiology Medical University of Warsaw
name: Marcin Grabowski, PhD
role: STUDY_CHAIR
References:
citation: Balsam P, Ozieranski K, Tyminska A, Glowczynska R, Peller M, Fojt A, Cacko A, Sieradzki B, Bakula E, Markulis M, Kowalik R, Huczek Z, Filipiak KJ, Opolski G, Grabowski M. The impact of torasemide on haemodynamic and neurohormonal stress, and cardiac remodelling in heart failure - TORNADO: a study protocol for a randomized controlled trial. Trials. 2017 Jan 23;18(1):36. doi: 10.1186/s13063-016-1760-z.