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Single Dose Study to Compare the Pharmacodynamics of Torasemide-PR 10 mg,Torasemide-IR 10 mg and Furosemide-IR 40 mg in Patients With Compensated Heart Failure

This study has been terminated.
(Slow recruitment)
Sponsor:
Information provided by (Responsible Party):
Ferrer Internacional S.A.
ClinicalTrials.gov Identifier:
NCT01549158
First received: March 6, 2012
Last updated: April 24, 2013
Last verified: April 2013
  Purpose

This is a randomized, open-label, blinded-endpoint, crossover, single dose study to compare the pharmacodynamics of Torasemide-PR 10 mg, Torasemide-IR10 mg and furosemide-IR 40 mg. 30 patients of both sexes with CHF with a maximum imbalance of 60:40% in either direction will be included in the study. Patients with compensated heart failure, grade II or III as defined by the European Society of Cardiology, with a duration of ≥ 3 months at the time of inclusion documented in the patient's record or patients who previously required diuretic therapy.

Principal variable will be the efficiency of sodium excretion that will be assessed as the ratio between the average drug-induced natriuresis and the average drug recovered in urine over 24 hours.

The difference between the efficiency of 24 hour sodium excretion following administration of torasemide PR and furosemide will be formally tested by means of a Students t-test for paired samples. The test will be two-sided at 5% significance level. Efficiency changes over time will also be assessed, however will not be subject to formal statistical testing.


Condition Intervention Phase
Compensated Heart Failure
Drug: torasemide-PR
Drug: Furosemide-IR
Drug: torasemide-IR
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized, Open-Label, Blinded-Endpoint, Crossover, Single Dose Study to Compare the Pharmacodynamics of Torasemide-PR 10 mg,Torasemide-IR 10 mg and Furosemide-IR 40 mg, in Patients With Compensated Heart Failure (CHF).

Resource links provided by NLM:


Further study details as provided by Ferrer Internacional S.A.:

Primary Outcome Measures:
  • The efficiency of sodium excretion [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Will be assessed as the ratio between the average drug-induced natriuresis and the average drug recovered in urine over 24 hours.


Secondary Outcome Measures:
  • Pharmacokinetic plasma parameters and pharmacokinetic urine parameters [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Pharmacokinetic plasma parameters (Cmax, AUC0-t, AUC0-∞, t ½, Vd / F, Cl / F), pharmacokinetic urine parameters (ERFco , Ae24h, Ae ∞) and urine pharmacodynamic variables will be presented descriptively with no formal statistical testing.


Enrollment: 8
Study Start Date: February 2012
Study Completion Date: December 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Torasemide PR 10 mg Drug: torasemide-PR
Single oral dose of torasemide PR 10 mg
Active Comparator: Furosemide-IR 40 mg Drug: Furosemide-IR
Single oral dose of furosemide IR 40 mg
Active Comparator: Torasemide-IR 10 mg Drug: torasemide-IR
Single oral dose of torasemide IR 10 mg

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able to understand the nature of the study.
  2. Obtain signed informed consent form approved by the Ethics Committee of the hospital (CEIC).
  3. Male and female, ≥ 18 years at the time of the informed consent signature.
  4. Patients with compensated heart failure, grade II or III as defined by the European Society of Cardiology, with a duration of ≥ 3 months at the time of inclusion documented in the patient's record or patients who previously required diuretic therapy.
  5. Patients with stable heart failure on drug therapy. Stable drug therapy is defined as not having introduced any new drug for heart failure within 4 weeks prior to inclusion. Drugs doses could be adjusted during the study with the exception of the diuretics
  6. Lab analysis results, vital signs and ECG within normal ranges or not considered clinically significant by the investigator.
  7. For women only, the patient must be:

    • postmenopausal (≥ 1 year) or sterilized or,
    • without risk of becoming pregnant, not lactating, have a negative pregnancy test at study entry and without intention of becoming pregnant during the study course and use effective contraception.

    Postmenopausal status is defined as 12 consecutive months of spontaneous amenorrhea or confirmed by the results of follicle stimulating hormone (FSH) > 40 mlU/mL or at least 6 months after oophorectomy (with or without hysterectomy) documented in the patients record.

  8. Body weight within the normal ranges (Quetelet's index between 19 and 30) expressed as weight (kg) /height (m2).

Exclusion Criteria:

  1. Hospitalization due to heart failure, acute coronary syndrome, myocardial infarction, cardiac catheterization, revascularization, cardiac arrhythmia, transient ischemic attack or stroke, cardiac arrhythmia within 6 weeks prior to inclusion or major surgery including cardiac thoracic or within 8 weeks prior to inclusion.
  2. Symptoms of angina at rest or with minimal activity (class III or IV, Canadian Cardiovascular Society).
  3. Severe aortic or mitral stenosis or clinically significant valvular heart disease that can lead to surgery within 12 months after inclusion.
  4. Hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis or clinically significant congenital heart disease.
  5. If ventricular assist devices, continuous inotropic therapy or hospitalization is considered necessary in case of refractory end-stage heart failure.
  6. Implementation of CRT within 3 months or cardioverter defibrillator in the 4 weeks before inclusion.
  7. High probability of receiving a heart transplant within 6 months after inclusion.
  8. Main organ transplant (ex. lungs, liver, kidney, heart, bone).
  9. Positive surface antigen of hepatitis B, hepatitis C or HIV or a known diagnosis of AIDS.
  10. Medical history or evidence of drug or alcohol abuse in the 3 months prior to inclusion.
  11. Concomitant cardiovascular disease that is expected to reduce life expectancy to less than one year.
  12. Scheduled routine iv infusions for heart failure (ex. inotropes, vasodilators, diuretics) or routine ultrafiltration.
  13. Digoxin therapy at steady state (approximately 6 hours post-dose) exceeding 1.0 ng/mL at inclusion.
  14. Chronic therapy with antiarrhythmic, antiepileptic drugs, eplerenone and espironolactone except amiodarone and beta-blockers.
  15. Current intake or within 14 days prior to inclusion of a potent inhibitor of CYP2C9
  16. Current intake or within 28 days prior to inclusion of a potent inducer of CYP2C9.
  17. Participation, in the 60 days or 5 half lives preceding the inclusion in the study, in other clinical trial.
  18. Systolic blood pressure > 150mm Hg diastolic blood pressure > 95 mmHg, confirmed on 2 separate visits before inclusion.
  19. Heart rate in supine > 100 beats/min after 5 minute rest or untreated symptomatic bradycardia within one month prior to inclusion.
  20. Total bilirubin > 1.5 times ULN, or ALT or AST > 3 times ULN.
  21. Estimated GFR > 30 ml/min/1.73 m2 calculated by the modification of diet in renal disease (RD).
  22. Chronic treatment with NSAIDs (> 7 days), except aspirin < 325 mg dose.
  23. Uncontrolled insulin-dependent diabetes.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01549158

Locations
Spain
Centre d'Investigació de Medicaments (CIM), Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Sponsors and Collaborators
Ferrer Internacional S.A.
  More Information

No publications provided

Responsible Party: Ferrer Internacional S.A.
ClinicalTrials.gov Identifier: NCT01549158     History of Changes
Other Study ID Numbers: P-110875-01
Study First Received: March 6, 2012
Last Updated: April 24, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Ferrer Internacional S.A.:
loop diuretics
torasemide prolonged release
torasemide immediate release
Sutril Neo
pharmacodynamic profile of Torasemide-PR

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Furosemide
Torsemide
Antihypertensive Agents
Cardiovascular Agents
Diuretics
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014