Investigator Initiated Randomized Open-label Comparative Study of Britomar (Prolonged Release Torasemide) and Diuver (Torasemide) to Assess Effects on Natriuresis and Central Hemodynamics.

Randomized Open-label Comparative Study of Britomar (Prolonged Release Torasemide) and Diuver (Torasemide) to Assess Effects on Natriuresis and Central Hemodynamics in Patients With Arterial Hypertension and Chronic Heart Failure

Study hypothesis is that the time from randomization to the increase of natriuresis (%), time to standardization of natriuresis daily profile, blood pressure profile and the percentage reduction of central hemodynamic parameters will be relatively changed over the study period by more than 15%.

Study Overview

• Status: Unknown
• Conditions: Chronic Heart Failure; Arterial Hypertension
• Intervention / Treatment: Drug: Prolonged release Torasemide (Britomar); Drug: Torasemide (Diuver)

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Grigory P Arutyunov, Prof; Phone Number: 007(495)952-73-77; Email: arut@ossn.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women in the age from 40 to 70 years.
2. Established diagnosis of II-III grade essential arterial hypertension
3. NYHA II-III chronic heart failure
4. Salt-sensitivity
5. Stable therapy for 3 months prior enrollment to the study including any diuretic, ACE-inhibitor, beta-blocker.
6. Signed informed consent for participation in the study.
7. Women with child-bearing potential should agree to use effective birth control methods from screening up to completion of the study, excluding situations when their sexual partner(s) are surgically sterilized, or whеn women do not have any sexual contacts. Effective methods of birth control are contraception methods which are used constantly and regularly (including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, diaphragms with spermicides, male or female condoms or cervical cap).

Exclusion Criteria:

1. Unlikely cooperation with a patient in the study period, disability
2. Identification of salt - resistance at screening
3. Patients that have had myocardial infarction, unstable angina pectoris, percutaneous coronary intervention heart failure, hypertensive encephalopathy, cerebrovascular accident (stroke) or transient ischaemic attack for the last 3 months.
4. Patients with severe heart failure (Stage IV of New York Heart Association), clinically significant aortic valve or mitral stenosis, uncorrected coarctation of the aorta, obstruction of cardiac output (obstructive hypertrophic cardiomyopathy)
5. Previous glomerulonephritis, severe pyelonephritis or another known severe renal disease which is confirmed by GFR < 40 ml/min/1.73 m2 calculated by Cockroft-Gault formula.
6. Secondary arterial hypertension, severe or uncontrolled AH at the study enrollment (BP> 180 mm Hg or DAP > 110 mm Hg)
7. Any severe, decompensated or unstable diseases or conditions which, on the investigator's opinion, endanger patient's life or aggravate disease prognosis (decompensated heart failure, anemia, severe diabetes mellitus, autoimmune, oncological diseases, hepatic, allergic reactions, connective tissue diseases, etc.)
8. Acute infectious diseases.
9. Hypersensitivity to components of Britomar or Diuver
10. Pregnancy, lactation period.
11. Participation in another clinical study for the last 30 days.
12. Scheduled coronary artery surgery (for example, stent implantation or coronary artery bypass grafting) or any other non-cardiological major surgery.
13. 13. Administration of drugs which affect natriuresis level (any diuretics which are not related with the study product). Patients are excluded from the study if they have taken the drugs for the last 48 years up to Visit D -10, in the screening period and/or treatment period/follow-up period of the study.
14. Use of narcotic drugs or alcohol abuse for the last 6 months and inability/unwillingness to refrain from narcotic drugs and excessive alcohol intake in the study period. The excessive alcohol intake is average alcohol >2 units of alcohol. A unit of alcohol for various beverages is 12 ounce (350 ml) of beer, 5 ounce (150 ml) of wine or 1.5 ounce (45 ml) of 80% alcohol.
15. Any other reason which would hinder patients' compliance with study requirements or their understanding of the study aim and potential risks of participation in study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prolonged release Torasemide (Britomar); Prolonged release Torasemide (Britomar) - round, biconvex, white to off-white tablets debossed SN with one side. 1 tablet contains active substance - torasemide 5 or 10 mg and excipients - guar gum, maize starch, anhydrous colloidal silica, magnesium stearate, lactose. Dosage scheme: per os, once a day, regardless of meals. The common starting dose in CHF - 10-20 mg once a day. If adequate diuretic effect is absent, the dose is increased approximately twofold up to adequate diuretic effect.	Drug: Prolonged release Torasemide (Britomar)
Active Comparator: Torasemide (Diuver); Torasemide (Diuver) - white to off-white, round, biconvex tablets. 1 tablet contain active substance - torasemide 5 or 10 mg and excipients - lactose monohydrate, maize starch, sodium glycolate starch, anhydrous colloidal silica, magnesium stearate. Dosage scheme: per os, once a day, after meals. Therapeutic dose - 5 mg a day. If necessary, a dose may be increased up to 20 mg a day, in some cases - up to 40 mg.	Drug: Torasemide (Diuver)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory markers excretion	15% or more increasing of the following Tamm-Horsfall protein, beta-2-microglobulin, osteoponin, TGF- β1 excretion in comperison with baseline level	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily sodium excretion	Increasing of daily sodium excretion on 30% or more in comparison with baseline	3 months
Augmentation index	Decreasing of augmentation index on 30 or more percents in comparison with baseline level	3 months
Albuminuria	Appearance of albuminuria of any stage or increasing of albuminuria level in case of existing albuminuria at the baseline. (measured by dipstick)	3 months

Collaborators and Investigators

• Sponsor: Society of Specialists in Heart Failure
• Investigators: Principal Investigator: Grigory P Arutyunov, Prof, Russian Society for Heart Failure

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Anticipated): May 1, 2015
• Study Completion (Anticipated): May 1, 2015

Study Registration Dates

• First Submitted: March 12, 2014
• First Submitted That Met QC Criteria: March 12, 2014
• First Posted (Estimate): March 14, 2014

Study Record Updates

• Last Update Posted (Estimate): March 20, 2014
• Last Update Submitted That Met QC Criteria: March 19, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Kidney damage hypertension cardiovascular diseases, congestive heart failure renal function natriuresis natriuresis monitoring
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Heart Failure; 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: TOR-IIT-001 (Other Grant/Funding Number: Investigator Initiated study. Grant was provided by Takeda Pharmaceuticals LLC, Russia)