Hypertension Study: Multinational Torasemide Trial in Mild to Moderate Hypertension.

Multicentre, Multinational, Parallel, Randomised, Double Blind Clinical Trial, to Evaluate the Non-inferiority of PR Torasemide Versus IR Torasemide in Patients With Mild or Moderate Arterial Hypertension.

Primary objective:To demonstrate the no-inferiority in efficacy of treatment with Torsemide-PR in relation to Torsemide-IR in patients with mild and/or moderate hypertension.

Secondary objectives: To evaluate the safety and tolerability of Torsemide-PR.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Torasemide Prolonged Release (loop diuretic); Drug: Torasemide Immediate Release (loop diuretic)

Detailed Description

Torsemide is a loop diuretic from the group of pyridine-sulfonylureas, which acts on the ascending large portion of the Henle loop where it inhibits the Na+/K+/2Cl- transport!system and blocks Cl- channels.Therefore, sodium and chlorine ions and water can not be reabsorbed in the tubule and the urine volume increases significantly. Torsemide is used for the treatment of oedema associated with congestive heart failure, kidney or liver disease and, either alone or combined with other anti-hypertensive drugs, for the treatment of arterial hypertension.

This trial compares the effect of a new formulation of Torasemide (Torasemide prolonged release)to the already available immediate release formulation of the same drug on the treatment of mild to moderate hypertensive patients.

Eligible patients will be randomised to either treatment with Torasemide prolonged release or with Torasemide immediate release and will be followed-up until completing 3 months of treatment.Blood pressure will be measured by an OMRON pressure gauge. Additionally, ABPM will be performed on a sub-group of the patients taking part in this trial.

• Study Type: Interventional
• Enrollment: 388
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged from 18 to 75, inclusive.

2. Ambulatory patients diagnosed with mild or moderate arterial hypertension complying with the following requirements:

   1. Patients diagnosed "de novo".
   2. Patients with prior anti-hypertensive treatment in monotherapy who do not respond to the treatment and, in the investigator's opinion, could benefit from diuretic treatment in monotherapy.
   3. Patients with prior anti-hypertensive treatment in monotherapy who do not tolerate the current treatment and, in the investigator's opinion, could benefit from diuretic treatment in monotherapy.

   Patients with prior treatment must be able to interrupt their present treatment for a period of up to 3 months.

   (Mild or moderate hypertension defined by blood pressure levels: Systolic blood pressure from 140-179 mm Hg and diastolic blood pressure from 90-109 mm Hg) (2003 European Society of Hypertension-European Society of Cardiology guidelines for management of arterial hypertension) (3)

3. Capable of understanding the nature of the trial.
4. Providing their informed consent in writing.

Exclusion Criteria:

1. Pregnant or breastfeeding women and women of fertile age who are not using a safe contraceptive method or do not intend to use one during the trial. Safe contraceptive methods are oral or parenteral contraceptive treatments or barrier methods: masculine or feminine condom, diaphragm and/or IUD.
2. Severe arterial hypertension (systolic blood pressure of 180 mmHg or above and diastolic blood pressure of 110 mmHg or above).
3. Known or suspected secondary arterial hypertension.
4. History of known hypersensitivity to the compound under study or to sulfonylureas.
5. History of repeated and documented hypertensive crises.
6. NYHA grade II to IV congestive heart failure.
7. Severe cardiac arrhythmia (sustained ventricular tachycardia, auricular fibrillation, auricular flutter, bradycardia under 45 beats per minute).
8. Unstable angina pectoris.
9. Acute myocardial infarct in the last 6 months.
10. Liver failure defined by the following analytical parameters: - SGPT (ALT) or SGOT (AST) over twice the upper normal limit.
11. Chronic kidney failure defined by the following analytical parameters: Serum creatinine over 2.3 mg/dl (or 203 mol/L).
12. Patients with insulin-dependent diabetes and patients with non-insulin dependent diabetes.
13. Cerebrovascular accident in the last 6 months.
14. Contraindications in the data obtained during the selection process in the physical examination, haematology, biochemistry, urine analysis and 12-lead ECG, in the investigator's opinion.
15. Simultaneous participation in another clinical trial or treatment with any investigational drug within the 30 days prior to signing the informed consent form.
16. Lactose intolerance.
17. Concomitant treatment with lithium.
18. Patients requiring chronic treatment (treatment > 7 days) with non-steroidal anti-inflammatory drugs, including aspirin.
19. Patients with concomitant treatment with aminoglycoside antibiotics, etacrynic acid.
20. Chronic administration of any medication affecting blood pressure.
21. Patients in treatment with group 1a, 1b or 2 anti-arrhythmic drugs.
22. History of drug or alcohol addiction within the 6 months prior to the start of the trial.
23. Any clinical circumstance or condition which, in the investigator's opinion, could affect the possibility of completing the protocol and the administration of Torasemide.
24. Obesity with a body mass index (BMI) of over 40 kg/m2.
25. Patients who do not respond to diuretic treatment in monotherapy.
26. Patients with prior anti-hypertensive treatment in monotherapy who are candidates for anti-hypertensive treatment in polytherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Difference in mm Hg between the mean diastolic blood pressure (DBP) values the baseline period and the values at the end of the treatment period.

Secondary Outcome Measures

Outcome Measure
Difference in mm Hg, systolic blood pressure (SBP) values in the baseline period and the values at the end of the treatment period.
Percentage of patients with controlled blood pressure (SBP < 140 and/or DBP < 90) at the end of the treatment period.
Urinary symptoms.
ABPM values measured in a subgroup of patients
Safety & tolerability.

Collaborators and Investigators

• Sponsor: Ferrer Internacional S.A.
• Investigators: Study Chair: Alex Roca, MD, PhD, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau; Principal Investigator: Antonio Coca, MD, PhD, H. Clínic Barcelona, Barcelona, Spain; Principal Investigator: Joaquim Vila, MD, Hospital Municipal de Badalona, Badalona, Barcelona, Spain; Principal Investigator: Javier Sobrino, MD, Hospital del Esperit Sant, Santa Coloma de Gramanet, Barcelona, Spain; Principal Investigator: Jaume Plana, MD, Hospital Residencia Sant Camil, Sant Pere de Ribes, Barcelona, Spain; Principal Investigator: Xavier Farres, MD, Centre d'Atenció Primaria El Remei de Vic, Vic, Barcelona, Spain; Principal Investigator: Joan Garcia, MD, PhD, Hospital Universitario La Paz; Principal Investigator: Manuel Luque, MD, Hospital Clinico San Carlos, Madrid, Spain; Principal Investigator: Luis De Teresa, MD, Hospital de Sant Vicenç de Raspeig, Sant Vicenç de Raspeig, Alicante, Spain; Principal Investigator: Jose Vicente, MD, Centro de Salud de Petrel, Petrel, Alicante, Spain; Principal Investigator: Angela Felip, MD, PhD, Hospital de Mataró, Mataró, Barcelona, Spain; Principal Investigator: Pedro Aranda, MD, PhD, Hospital Universitario Carlos Haya, Málaga, Spain; Principal Investigator: Pablo Gómez, MD, PhD, Hospital de Jerez de la Frontera, Cádiz, Spain; Principal Investigator: Blas Gil, MD, Hospital Clínico Universitario San Cecilio, Granada, Spain; Principal Investigator: Joaquín Aracil, MD, Centro de Salud El Cristo, Oviedo, Asturias, Spain; Principal Investigator: Miguel A Prieto, MD, Centro de Salud Vallobin Concinos, Oviedo, Asturias, Spain; Principal Investigator: Carles Brotons, MD, PhD, Centre d'Atenció Primaria Sardenya, Barcelona, Spain; Principal Investigator: Félix Laporta, MD, Centro de Salud La Roda, La Roda, Albacete, Spain; Principal Investigator: José A División, MD, Centro de Salud de Fuentealbilla, Fuentealbilla, Albacete, Spain; Principal Investigator: Enrique López, MD, Centro de Salud de Chinchilla, Chinchilla, Albacete, Spain; Principal Investigator: Carlos Calvo, MD, PhD, Hospital Universitario de Santiago, Santiago de Compostela, Spain; Principal Investigator: Emili Marco, MD, Centre d'Atenció Primaria de Sarrià de Ter, Sarrià de Ter, Girona, Spain; Principal Investigator: Joan Martorell, MD, Centre de Salut de Guisona, Guisona, Lleida, Spain; Principal Investigator: Montserrat Pujol, MD, Centre d'Atenció Primaria El Carmel, Barcelona, Spain; Principal Investigator: Raquel Adroer, MD, Centre d'Atenció Primaria Florida Nord, Barcelona, Spain; Principal Investigator: Angel Cano, MD, Centre d'Atenció Primaria Bon Pastor, Barcelona, Spain; Principal Investigator: Nadezhda S Alexeeva, PhD, St. Petersburg Cardiology Clinic, St. Petesburg, Russia; Principal Investigator: Andrei Y Baranovsky, MD, PhD, St. Petersburg City Hospital #31, St. Petesburg, Russia; Principal Investigator: Svetlana A Boldueva, MD, PhD, St. Petersburg Mechnikov State Medical Academy, St. Petesburg, Russia; Principal Investigator: Svetlana K Churina, MD, PhD, Pokrovskaya Hospital, 1-st and 2-nd Cardiology Department, St. Petesburg, Russia; Principal Investigator: Boris M Goloschekin, MD, PhD, St. Petersburg City Hospital #15, St. Petesburg, Russia; Principal Investigator: Yanis Y Dumpis, MD, St.Petersburg Mechnikov State Medical Academy North-West Center of Arrhythmia Diagnostics and Treatment, St. Petesburg, Russia; Principal Investigator: Konstantin N Zrazhevsky, MD, PhD, St.Petersburg City Hospital #8, St. Petesburg, Russia; Principal Investigator: Victor Kostenko, MD, PhD, St.Petersburg City Outpatient Unit #109, St. Petesburg, Russia; Principal Investigator: Elena F Pavlysh, MD, PhD, St.Petersburg City Outpatient Unit #25, St. Petesburg, Russia; Principal Investigator: Lev A Sorokin, MD, PhD, St. Elizabeth City Hospital, St. Petesburg, Russia; Principal Investigator: Irina A Zobenko, MD, JSC Chernaya Rechka Health Center, St. Petesburg, Russia; Principal Investigator: Alexander O Sherenkov, MD, PhD, Krasnogvardeysky District Medical-Physiology Clinic, St. Petesburg, Russia; Principal Investigator: Alexander V Orlov-Morozov, MD, PhD, Moscow City Hospital #23, Moscow, Russia; Principal Investigator: Vladimir A Parfenov, MD, PhD, Moscow City Hospital #61, Moscow, Russia; Principal Investigator: Victor A Milyagin, MD, PhD, Smolensk State Medical Academy, Smolensk, Russia

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Study Completion: February 1, 2006

Study Registration Dates

• First Submitted: June 6, 2006
• First Submitted That Met QC Criteria: June 6, 2006
• First Posted (Estimate): June 7, 2006

Study Record Updates

• Last Update Posted (Estimate): March 6, 2015
• Last Update Submitted That Met QC Criteria: March 5, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Hypertension; Diuretic; Anti-hypertensive effect
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Torsemide
• Other Study ID Numbers: P030089-01; EudraCT: 2004-000876-14