Clinical trial NCT00334386: Hypertension Study: Multinational Torasemide Trial in Mild to Moderate Hypertension.
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Keywords: Hypertension
Anti-hypertensive effect
Diuretic
Lead sponsor: Ferrer Internacional S.A.
Sponsor class: INDUSTRY
First posted: 2006-06-07
Enrollment: 388
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
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 outcomes:
measure: Difference in mm Hg, systolic blood pressure (SBP) values in the baseline period and the values at the end of the treatment period.
measure: Percentage of patients with controlled blood pressure (SBP < 140 and/or DBP < 90) at the end of the treatment period.
measure: Urinary symptoms.
measure: ABPM values measured in a subgroup of patients
measure: Safety & tolerability.
Other outcomes:
Locations:
Study officials:
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Alex Roca, MD, PhD
role: STUDY_CHAIR
affiliation: H. Clínic Barcelona, Barcelona, Spain
name: Antonio Coca, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Municipal de Badalona, Badalona, Barcelona, Spain
name: Joaquim Vila, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital del Esperit Sant, Santa Coloma de Gramanet, Barcelona, Spain
name: Javier Sobrino, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Residencia Sant Camil, Sant Pere de Ribes, Barcelona, Spain
name: Jaume Plana, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre d'Atenció Primaria El Remei de Vic, Vic, Barcelona, Spain
name: Xavier Farres, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario La Paz
name: Joan Garcia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínico San Carlos, Madrid, Spain
name: Manuel Luque, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Sant Vicenç de Raspeig, Sant Vicenç de Raspeig, Alicante, Spain
name: Luis De Teresa, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro de Salud de Petrel, Petrel, Alicante, Spain
name: Jose Vicente, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Mataró, Mataró, Barcelona, Spain
name: Angela Felip, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Carlos Haya, Málaga, Spain
name: Pedro Aranda, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Jerez de la Frontera, Cádiz, Spain
name: Pablo Gómez, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clínico Universitario San Cecilio, Granada, Spain
name: Blas Gil, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro de Salud El Cristo, Oviedo, Asturias, Spain
name: Joaquín Aracil, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro de Salud Vallobin Concinos, Oviedo, Asturias, Spain
name: Miguel A Prieto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre d'Atenció Primaria Sardenya, Barcelona, Spain
name: Carles Brotons, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro de Salud La Roda, La Roda, Albacete, Spain
name: Félix Laporta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro de Salud de Fuentealbilla, Fuentealbilla, Albacete, Spain
name: José A División, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro de Salud de Chinchilla, Chinchilla, Albacete, Spain
name: Enrique López, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario de Santiago, Santiago de Compostela, Spain
name: Carlos Calvo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre d'Atenció Primaria de Sarrià de Ter, Sarrià de Ter, Girona, Spain
name: Emili Marco, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre de Salut de Guisona, Guisona, Lleida, Spain
name: Joan Martorell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre d'Atenció Primaria El Carmel, Barcelona, Spain
name: Montserrat Pujol, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre d'Atenció Primaria Florida Nord, Barcelona, Spain
name: Raquel Adroer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre d'Atenció Primaria Bon Pastor, Barcelona, Spain
name: Angel Cano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Petersburg Cardiology Clinic, St. Petesburg, Russia
name: Nadezhda S Alexeeva, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Petersburg City Hospital #31, St. Petesburg, Russia
name: Andrei Y Baranovsky, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Petersburg Mechnikov State Medical Academy, St. Petesburg, Russia
name: Svetlana A Boldueva, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pokrovskaya Hospital, 1-st and 2-nd Cardiology Department, St. Petesburg, Russia
name: Svetlana K Churina, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Petersburg City Hospital #15, St. Petesburg, Russia
name: Boris M Goloschekin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St.Petersburg Mechnikov State Medical Academy North-West Center of Arrhythmia Diagnostics and Treatment, St. Petesburg, Russia
name: Yanis Y Dumpis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St.Petersburg City Hospital #8, St. Petesburg, Russia
name: Konstantin N Zrazhevsky, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St.Petersburg City Outpatient Unit #109, St. Petesburg, Russia
name: Victor Kostenko, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St.Petersburg City Outpatient Unit #25, St. Petesburg, Russia
name: Elena F Pavlysh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Elizabeth City Hospital, St. Petesburg, Russia
name: Lev A Sorokin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: JSC Chernaya Rechka Health Center, St. Petesburg, Russia
name: Irina A Zobenko, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Krasnogvardeysky District Medical-Physiology Clinic, St. Petesburg, Russia
name: Alexander O Sherenkov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Moscow City Hospital #23, Moscow, Russia
name: Alexander V Orlov-Morozov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Moscow City Hospital #61, Moscow, Russia
name: Vladimir A Parfenov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Smolensk State Medical Academy, Smolensk, Russia
name: Victor A Milyagin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: