Endothelin-1 Receptor Blockade in Resistant Hypertension

NCT04388124 | Recruiting Phase 2

• 1 other identifier: 2018/0350/HP
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Keywords

endothelin-1

Outcome Measures

Primary Outcomes (1)

• assess the effect of ET-1 receptor antagonist administration during 8 weeks on endothelial function in patients with resistant hypertension.

  8-week change in amplitude of endothelium-dependent radial artery dilatation with sustained increase in blood flow

  through study completion, an average of 22 months

Secondary Outcomes (3)

• assess the effect of the administration of an ET-1 receptor antagonist during 8 weeks on systemic and central hemodynamics

  through study completion, an average of 22 months

• assess the effect of the administration of an ET-1 receptor antagonist during 8 weeks on local concentrations of endothelial factors during a sustained increase of the blood flow

  through study completion, an average of 22 months

• assess the effect of the administration of an ET-1 receptor antagonist during 8 weeks on the renal function of patients with resistant hypertension.

  through study completion, an average of 22 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Bosentan

EXPERIMENTAL

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.

Drug: Bosentan

Interventions

Bosentan DRUG

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

Bosentan

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Patient who read and understood the newsletter and signed the consent form
• Patient affiliated to a social security scheme

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (1)

Chu Rouen

Rouen, 76031, France

RECRUITING

MeSH Terms

Interventions

Bosentan

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Modification of the pharmaceutical form, removal from the primary packaging and repackaging-\> tablet of Bosentan will be encapsuled. The pharmaceutical form of placebo and bosentant will be identical
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2020
• First Posted: May 14, 2020
• Study Start: October 20, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

FR (1)