Back to resultsVASCULAR AND RENAL IMPACT OF ENDOTHELIN-1 RECEPTOR BLOCKADE IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION (ENDOTHELIN-2)
Primary Purpose
Resistant Hypertension
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Bosentan
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Resistant Hypertension focused on measuring endothelin-1
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Placebo
Bosentan
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04388124
Brief Title
VASCULAR AND RENAL IMPACT OF ENDOTHELIN-1 RECEPTOR BLOCKADE IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION
Acronym
ENDOTHELIN-2
Official Title
VASCULAR AND RENAL IMPACT OF ENDOTHELIN-1 RECEPTOR BLOCKADE IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Unknown status
Study Start Date
September 2020 (Anticipated)
Primary Completion Date
November 2022 (Anticipated)
Study Completion Date
November 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Rouen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Resistant Hypertension
Keywords
endothelin-1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
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
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Bosentan
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bosentan
Intervention Description
vascular assesment Clinical exam urinary analysis blood results natriuresis and measured glomerular filtration rate
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
assess the effect of ET-1 receptor antagonist administration during 8 weeks on endothelial function in patients with resistant hypertension.
Description
8-week change in amplitude of endothelium-dependent radial artery dilatation with sustained increase in blood flow
Time Frame
through study completion, an average of 22 months
Secondary Outcome Measure Information:
Title
assess the effect of the administration of an ET-1 receptor antagonist during 8 weeks on systemic and central hemodynamics
Description
8 week change in peripheral and central arterial pressures and arterial stiffness
Time Frame
through study completion, an average of 22 months
Title
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
Description
8-week change in local concentrations of NO, EETs and ET-1 with sustained increase in blood flow
Time Frame
through study completion, an average of 22 months
Title
assess the effect of the administration of an ET-1 receptor antagonist during 8 weeks on the renal function of patients with resistant hypertension.
Description
Variation in 8 weeks of natriuresis and measured glomerular filtration rate (DTPA labeled by the technetium 99m)
Time Frame
through study completion, an average of 22 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
12. IPD Sharing Statement
Learn more about this trial
VASCULAR AND RENAL IMPACT OF ENDOTHELIN-1 RECEPTOR BLOCKADE IN PATIENTS WITH RESISTANT ARTERIAL HYPERTENSION
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