Resistant arterial hypertension MedDRA version: 20.0 Level: HLT Classification code 10038466 Term: Renal hypertension and related conditions System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 20.0 Level: HLT Classification code 10038465 Term: Renal hypertensions System Organ Class: 100000004866 MedDRA version: 21.1 Level: PT Classification code 10038464 Term: Renal hypertension System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Trade Name: BOSENTAN MYLAN
Product Name: BOSENTAN MYLAN
Pharmaceutical Form: Capsule, soft
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use
Sponsors
CHU de Rouen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • age between 30 and 80 years old • Patients with resistant hypertension defined according to the criteria recognized by the French Society of Hypertension (SFHTA): arterial pressure greater than or equal to 140 and / 90 mm Hg under triple antihypertensive trithérapie at optimal dose comprising at least one diuretic pendant at less than 4 weeks. • Patients with resistant hypertension confirmed by self-measurement (=135 / 85 mmHg on average) or by ambulatory blood pressure measurement (mean of 24h =130 / 80 mmHg). • Hemoglobin level = 12 g / dL • For women of childbearing potential, reliable methods of contraception (as defined by the WHO-Pearl Index) should be used (hormonal contraception should not be the only contraceptive method used during bosentan treatment). • For postmenopausal women: confirmatory diagnosis (non-medically induced amenorrhea for at least 12 months and age greater than 45, before the inclusion visit) • Patient who read and understood the newsletter and signed the consent form • Patient affiliated to a social security scheme Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: Patients aged 30 to 80 years • Patients with hypertension • Patients with secondary arterial hypertension other than sleep apnea syndrome or chronic renal failure stage 2 or 3. • Patients with hypertension greater than or equal to 180 and / or 110mmHg • Chronic renal failure stage 4 and 5 (defined by DFG CKD-EPI 20mmHg and / or DBP> 10mmHg occurring within 3 minutes of standing). • Contra-indication to NATISPRAY 0.30 mg / dose, oral spray solution (including nitrate hypersensitivity) in accordance with the NATISPRAY SPC: o shock, severe hypotension, o in combination with sildenafil o obstructive cardiomyopathy, o inferior court inferior myocardial infarction with right ventricular extension, except in case of evidence of left ventricular failure, o intracranial hypertension, • Contra-indication to BOSENTAN MYLAN 62.5 mg and 125 mg film-coated tablets: o Hypersensitivity to the active substance or to any of the excipients listed in the SPC Moderate to severe hepatic insufficiency corresponding to class B or C of the Child-Pugh classification o Serum levels of liver aminotransferases, ASAT and / or ALAT> 3 times the upper limit of normal at start of treatment (results less than 3 months old). o Association with ciclosporin A • Known allergy to cellulose • Patients treated with: tacrolimus or sirolimus, fluconazole or other CYP2C9 or CYP3A4 inhibitors, glibenclamide, rifampicin, antiretroviral drugs including lopinavir + ritonavir, warfarin, simvastatin, ketoconazole, epoprostenol, sildenafil and digoxin • Pregnant, breastfeeding woman, or woman of childbearing potential not using reliable methods of contraception (hormonal contraception should not be the only contraceptive method used during bosentan treatment) or no proven reliable effective contraception; • Person deprived of liberty by an administrative or judicial decision or person placed under the protection of justice, under tutorship or curatorship • Patient participating or having participated in the 4 weeks prior to inclusion in a clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of the study is to assess the effect of ET-1 receptor antagonist administration during 8 weeks on endothelial function in patients with resistant hypertension. ;Secondary Objective: The secondary objectives are to assess the effect of the administration of an ET-1 receptor antagonist during 8 weeks: - on systemic and central hemodynamics - on local concentrations of endothelial factors during a sustained increase of the blood flow - on the renal function of patients with resistant hypertension. ;Primary end point(s): 8-week change in amplitude of endothelium-dependent radial artery dilatation with sustained increase in blood flow ;Timepoint(s) of evaluation of this end point: 8 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - 8 week change in peripheral and central arterial pressures and arterial stiffness - 8-week change in local concentrations of NO, EETs and ET-1 with sustained increase in blood flow - Variation in 8 weeks of natriuresis and measured glomerular filtration rate (DTPA labeled by the technetium 99m);Timepoint(s) of evaluation of this end point: 8 weeks | — |
Countries
France
Contacts
Public ContactPOURCHER
CHU de Rouen
Outcome results
None listed