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

Condition(s) targeted: Hypertension

Intervention: Torasemide Prolonged Release (loop diuretic) (Drug); Torasemide Immediate Release (loop diuretic) (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Ferrer Internacional S.A.

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

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.

Official title: 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.

Study design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: 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:

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.

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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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.

Starting date: April 2005
Ending date: February 2006
Last updated: June 6, 2006