Resistant HypertensionPhase 2ENDOTHELIN-2NCT04388124
Endothelin-1 Receptor Blockade in Resistant Hypertension
A Phase 2 study testing Bosentan in people with Resistant Hypertension, run by University Hospital, Rouen at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Resistant Hypertension
- What is being tested?
- Bosentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteFrance
- Study dates
- 20 Oct 2021to Aug 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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).
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Chu Rouen
Rouen, 76031
Ludivine Lebourg, Dr, 02 32 88 90 02, Ludivine.Lebourg@chu-rouen.fr
Ludivine Lebourg, Dr
About this study
Official title: VASCULAR AND RENAL IMPACT OF ENDOTHELIN-1 RECEPTOR BLOCKADE IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION
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
- Being tested
- Bosentan, Placebo
- Keywords
- endothelin-1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
vascular assesment Clinical exam urinary analysis blood results natriuresis and measured glomerular filtration rate
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Bosentan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
8 week change in peripheral and central arterial pressures and arterial stiffness
Measured: 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
8-week change in local concentrations of NO, EETs and ET-1 with sustained increase in blood flow
Measured: 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.
Variation in 8 weeks of natriuresis and measured glomerular filtration rate (DTPA labeled by the technetium 99m)
Measured: through study completion, an average of 22 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2020
- Study start20 Oct 2021
- Primary completionAug 2026 (estimated)
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Resistant HypertensionStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04388124
- Sponsor's protocol ID
- 2018/0350/HP
- Acronym
- ENDOTHELIN-2
- Status last verified
- Feb 2026
- First submitted
- 11 May 2020
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- VASCULAR AND RENAL IMPACT OF ENDOTHELIN-1 RECEPTOR BLOCKADE IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION
- ClinicalTrials.gov ID
- NCT04388124
- Acronym / sponsor ID
- ENDOTHELIN-2 / 2018/0350/HP
- Conditions
- Resistant Hypertension
- Keywords
- endothelin-1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- 20 Oct 2021 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 14 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPatient 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. |
| Bosentan | Experimental | Drug: BosentanPatient 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bosentanvascular assesment Clinical exam urinary analysis blood results natriuresis and measured glomerular filtration rate | Drug | Bosentan |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
assess the effect of ET-1 receptor antagonist administration during 8 weeks on endothelial function in patients with resistant hypertension.
Time frame: through study completion, an average of 22 months
8-week change in amplitude of endothelium-dependent radial artery dilatation with sustained increase in blood flow
3 secondary outcomes
assess the effect of the administration of an ET-1 receptor antagonist during 8 weeks on systemic and central hemodynamics
Time frame: 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
Time frame: 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.
Time frame: through study completion, an average of 22 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bosentan in people with Resistant Hypertension, run by University Hospital, Rouen at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
assess the effect of ET-1 receptor antagonist administration during 8 weeks on endothelial function in patients with resistant hypertension. (time frame: through study completion, an average of 22 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026; AzTrials last refreshed its copy on 3 Nov 2026.