VASCULAR AND RENAL IMPACT OF ENDOTHELIN-1 RECEPTOR BLOCKADE IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION

NCT ID: NCT04388124

Last Updated: 2020-05-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-30
• Study Completion Date: 2022-11-30

Brief Summary

The management of patients with resistant arterial hypertension, who are characterized by a very high cardiovascular risk, remains a major therapeutic issue. The use of endothelin-1 (ET-1) receptor antagonists, in addition to lowering blood pressure, may also improve endothelial function in these patients. The objective of this study is to assess the vascular impact of an ET-1 receptor antagonist on vascular function and systemic and central hemodynamics in patients with resistant arterial hypertension and ensure their good renal tolerance.

Conditions

Resistant Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Patient will receive placebo for 56 days: 2 capsules of 62.5 mg per day for 27 days +/-1 day, 2 capsules of 125 mg per day for 27 days +/-1 day.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Bosentan

Patient will receive Bosentan for 56 days: 2 capsules of 62.5 mg per day for 27 days +/-1 day, 2 capsules of 125 mg per day for 27 days +/-1 day.

Group Type: EXPERIMENTAL

Bosentan

Intervention Type: DRUG

vascular assesment Clinical exam urinary analysis blood results natriuresis and measured glomerular filtration rate

Interventions

Bosentan

vascular assesment Clinical exam urinary analysis blood results natriuresis and measured glomerular filtration rate

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility 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 therapy 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

Exclusion Criteria

• 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 <30 ml / min / 1,73m²)
• Renal transplant patient XML File Identifier: CEyMau8sPo+QFyOLD1ZEY3ZGFow= Page 11/22
• Orthostatic hypotension (decreased SBP> 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:

• shock, severe hypotension,
• in combination with sildenafil
• obstructive cardiomyopathy,
• inferior court inferior myocardial infarction with right ventricular extension, except in case of evidence of left ventricular failure,
• intracranial hypertension,

• Contra-indication to BOSENTAN MYLAN 62.5 mg and 125 mg filmcoated tablets:
• 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
• 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).
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Rouen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

2018/350/HP

Identifier Type: -

Identifier Source: org_study_id