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ENDOTHELION Study Group: Effect of Bosentan in NAION Patients (ENDOTHELION)

Primary Purpose

Ischemic Optic Neuropathy

Status

Recruiting

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

bosentan

placebo

About this trial

This is an interventional treatment trial for Ischemic Optic Neuropathy focused on measuring Bosentan

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Non arteritic ischemic optic neuropathy (NAION) with onset < 21 days
Age ≥ 50 years old
Signed informed consent form
Patients affiliated with a national health insurance scheme or beneficiaries of such a scheme

Exclusion Criteria:

Pregnant women, women in labour or breast-feeding mother
Patients with other acute or chronic intercurrent ocular pathology interfering with visual acuity or visual field (diabetes, drug-induced or other retinopathy, other optic neuropathy including uni- or contralateral glaucoma and/or intraocular pressure > 30 mmHg, advanced cataract, corneal opacities, amblyopia < 5/10, severe myopia > -6 diopters, retinal disease)
Simultaneous bilateral NAAION, 1 month apart or less
Signs that may raise suspicion of other inflammatory neuropathy: arterial NAAION (Horton's disease), pain on eye movement or any signs suggestive of optic neuritis, known diagnosis of multiple sclerosis, history of inflammatory optic neuropathy (homo- or ipsi-lateral). A temporal artery biopsy should be performed if there are symptoms suggestive of Horton's disease, or if there is pale and/or diffuse edema, or obliteration of the associated central retinal artery.
Patients with systolic blood pressure below 100 mmHg
Patient with orthostatic hypotension (20 mmHg drop in SBP and/or 10 mmHg drop in DBP when moving to a standing position)
Neurological history of vascular or tumour-related changes to the visual field or other optic neuropathy
Systemic inflammatory disease
Known allergy to bosentan
Patients with moderate to severe hepatic impairment (Child-Pugh class B or C), biliary cirrhosis (serum levels of liver aminotransferases, aspartate aminotransferases (ASAT) and/or alanine aminotransferases (ALAT), greater than three times the upper limit of normal, bilirubin greater than twice normal)
Estimated glomerular filtration rate (GFR) < 30 ml/min/1.73 m2
Patients treated with drugs whose efficacy may be reduced by activation of cytochrome P450, 2C9, 3A4 and 2C19 isoenzymes
Patients treated with amiodarone
Patient treated with systemic corticosteroids (background treatment or treatment initiated at the time of NAAION diagnosis)
Person deprived of liberty by judicial or administrative decision, adult protected by law, hospitalized person
Ongoing participation in another clinical research study or in the exclusion period of another clinical study

Sites / Locations

University Hospital of AngersRecruiting
University Hospital of Bordeaux
CHU de GrenobleRecruiting
University Hospital of Grenoble MichallonRecruiting
Ophtalmological fondation of Rothschild + Bichat HospitalRecruiting
Centre National d'Ophtalmologie XV-XXRecruiting
University hospital of Saint-EtienneRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Bosentan

Placebo

Arm Description

Bosentan at a dose of 125 mg two times daily, will be administered orally, twice a day, during eight weeks

placebo drug , twice a day, during eight weeks

Outcomes

Primary Outcome Measures

mean deviation of automated visual field

Humphrey 30-2 SITA-standard

Secondary Outcome Measures

visual acuity

ETDRS scale

optic nerve fiber layer thickness

OCT measurement

mean deviation of automated visual field for healthy eye and NAION eye

Humphrey 30-2

inflammatory marker and prepro-endothelin dosing

RANTES, MCP-1, TNF-α, INF-γ, IL-6, IL-10 and TGF-β

mean deviation of automated visual field for controlateral eye

Humphrey 30-2 sita-standard

VFQ-25 score

VFQ-25 quality of life

rate of bilateral occurence of NAION

rate of bilateralization

Full Information

NCT ID

NCT02377271

First Posted

December 5, 2014

Last Updated

July 4, 2022

Sponsor

University Hospital, Grenoble

1. Study Identification

Unique Protocol Identification Number

NCT02377271

Brief Title

ENDOTHELION Study Group: Effect of Bosentan in NAION Patients

Acronym

ENDOTHELION

Official Title

Effect of Bosentan in Patients With Non Arteritic Ischemic Optic Neuropathy

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

August 2015 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Grenoble

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Acute ischemic optic neuropathy are the second leading cause of optic neuropathy after glaucoma in the population aged over 50 years. The visual prognosis of the condition is unfavorable in the great majority of cases, with significant effects on the visual field and vision. The severity of the unilateral condition is also associated with bilateralization in 15% at 5 years. There is no effective treatment for the acute phase of the disease or to reduce the rate of bilateralization. In this context, it is essential to develop new therapeutic strategies in the acute phase of the disease to reduce the anatomical optic nerve damage.

Detailed Description

The main objective of our study will be to compare the treatment with bosentan to placebo for 8 weeks for recovery anatomical criteria (RFNL in OCT, optic atrophy) and functional (visual acuity, visual field). The primary endpoint will be the improvement of the visual field, a major criterion of the affected visual function in this disease. The evaluation of bosentan will mainly after 8 weeks of treatment in order to assess the effectiveness of drug treatment in the absence of continuous positive airway pressure (set up after three months if necessary, feasible confounding factor for the evaluation of results ), the period of three months is sufficient to assess the anatomical and functional recovery (disappearance of papilledema).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ischemic Optic Neuropathy

Keywords

Bosentan

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

86 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Bosentan

Arm Type

Experimental

Arm Description

Bosentan at a dose of 125 mg two times daily, will be administered orally, twice a day, during eight weeks

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

placebo drug , twice a day, during eight weeks

Intervention Type

Drug

Intervention Name(s)

bosentan

Intervention Description

treatment by bosentan or placebo is randomized , 125 mg twice a day

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

treatment by bosentan or placebo is randomized

Primary Outcome Measure Information:

Title

mean deviation of automated visual field

Description

Humphrey 30-2 SITA-standard

Time Frame

3 month

Secondary Outcome Measure Information:

Title

visual acuity

Description

ETDRS scale

Time Frame

6, 12 and 24 month

Title

optic nerve fiber layer thickness

Description

OCT measurement

Time Frame

3, 6, 12 and 24 month

Title

mean deviation of automated visual field for healthy eye and NAION eye

Description

Humphrey 30-2

Time Frame

3, 6, 12 and 24 month

Title

inflammatory marker and prepro-endothelin dosing

Description

RANTES, MCP-1, TNF-α, INF-γ, IL-6, IL-10 and TGF-β

Time Frame

3 month

Title

mean deviation of automated visual field for controlateral eye

Description

Humphrey 30-2 sita-standard

Time Frame

24 month

Title

VFQ-25 score

Description

VFQ-25 quality of life

Time Frame

3 and 12 month

Title

rate of bilateral occurence of NAION

Description

rate of bilateralization

Time Frame

at 24 month visit

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Non arteritic ischemic optic neuropathy (NAION) with onset < 21 days Age ≥ 50 years old Signed informed consent form Patients affiliated with a national health insurance scheme or beneficiaries of such a scheme Exclusion Criteria: Pregnant women, women in labour or breast-feeding mother Patients with other acute or chronic intercurrent ocular pathology interfering with visual acuity or visual field (diabetes, drug-induced or other retinopathy, other optic neuropathy including uni- or contralateral glaucoma and/or intraocular pressure > 30 mmHg, advanced cataract, corneal opacities, amblyopia < 5/10, severe myopia > -6 diopters, retinal disease) Simultaneous bilateral NAAION, 1 month apart or less Signs that may raise suspicion of other inflammatory neuropathy: arterial NAAION (Horton's disease), pain on eye movement or any signs suggestive of optic neuritis, known diagnosis of multiple sclerosis, history of inflammatory optic neuropathy (homo- or ipsi-lateral). A temporal artery biopsy should be performed if there are symptoms suggestive of Horton's disease, or if there is pale and/or diffuse edema, or obliteration of the associated central retinal artery. Patients with systolic blood pressure below 100 mmHg Patient with orthostatic hypotension (20 mmHg drop in SBP and/or 10 mmHg drop in DBP when moving to a standing position) Neurological history of vascular or tumour-related changes to the visual field or other optic neuropathy Systemic inflammatory disease Known allergy to bosentan Patients with moderate to severe hepatic impairment (Child-Pugh class B or C), biliary cirrhosis (serum levels of liver aminotransferases, aspartate aminotransferases (ASAT) and/or alanine aminotransferases (ALAT), greater than three times the upper limit of normal, bilirubin greater than twice normal) Estimated glomerular filtration rate (GFR) < 30 ml/min/1.73 m2 Patients treated with drugs whose efficacy may be reduced by activation of cytochrome P450, 2C9, 3A4 and 2C19 isoenzymes Patients treated with amiodarone Patient treated with systemic corticosteroids (background treatment or treatment initiated at the time of NAAION diagnosis) Person deprived of liberty by judicial or administrative decision, adult protected by law, hospitalized person Ongoing participation in another clinical research study or in the exclusion period of another clinical study

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Christophe Pr CHIQUET, Prof, MD, PhD

CChiquet@chu-grenoble.fr

First Name & Middle Initial & Last Name or Official Title & Degree

BOUZEID Mayssam, PhD

Phone

+33 476766660

mbouzeid@chu-grenoble.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christophe Pr CHIQUET, Prof, MD, PhD

Organizational Affiliation

University Hospital, Grenoble

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital of Angers

City

Angers

ZIP/Postal Code

49100

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Philippe GOHIER, MD

Phone

0241353274

phgohier@chu-angers.fr

First Name & Middle Initial & Last Name & Degree

Frédéric GAGNADOUX, MD

First Name & Middle Initial & Last Name & Degree

Pascaline PRIOU, MD

First Name & Middle Initial & Last Name & Degree

Philippe GOHIER, MD

Facility Name

University Hospital of Bordeaux

City

Bordeaux

ZIP/Postal Code

33000

Country

France

Individual Site Status

Terminated

Facility Name

CHU de Grenoble

City

Grenoble

ZIP/Postal Code

38043

Country

France

Individual Site Status

Recruiting

Facility Name

University Hospital of Grenoble Michallon

City

Grenoble

ZIP/Postal Code

38043

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christophe CHIQUET, MD

Phone

04 76 76 55 16

CChiquet@chu-grenoble.fr

First Name & Middle Initial & Last Name & Degree

Jean-Louis PEPIN, MD

First Name & Middle Initial & Last Name & Degree

Renaud TAMISIER, MD

First Name & Middle Initial & Last Name & Degree

Sandrine LAUNOIS-ROLLINAT, MD

First Name & Middle Initial & Last Name & Degree

Bertrand TOUSSAINT, MD

First Name & Middle Initial & Last Name & Degree

Olivier ORMEZZANO, MD

First Name & Middle Initial & Last Name & Degree

Christophe CHIQUET, MD

First Name & Middle Initial & Last Name & Degree

Claire GAILLARD-GROLEAS, MD

Facility Name

Ophtalmological fondation of Rothschild + Bichat Hospital

City

Paris

ZIP/Postal Code

75019

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Catherine VIGNAL, MD

Phone

0148036222

cvignal@fo-rothschild.fr

First Name & Middle Initial & Last Name & Degree

Cédric LAMIREL, MD

First Name & Middle Initial & Last Name & Degree

Marie-Pia ORTHO, MD

First Name & Middle Initial & Last Name & Degree

Catherine VIGNAL, MD

Facility Name

Centre National d'Ophtalmologie XV-XX

City

Paris

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Catherine VIGNAL, MD

cvignal@club-internet.fr

First Name & Middle Initial & Last Name & Degree

Emmanuel HERON, MD

First Name & Middle Initial & Last Name & Degree

Catherine VIGNAL, MD

Facility Name

University hospital of Saint-Etienne

City

Saint-Etienne

ZIP/Postal Code

42055

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Philippe GAIN, MD

Phone

0477127793

philippe.gain@univ-st-etienne.fr

First Name & Middle Initial & Last Name & Degree

Claire GUILLEMOT, MD

Phone

0673169519

claire.guillemot@gmail.com

First Name & Middle Initial & Last Name & Degree

Gilles THURET, MD

First Name & Middle Initial & Last Name & Degree

Isabelle COURT-FORTUNE, MD

First Name & Middle Initial & Last Name & Degree

Marie Caroline TRONE, MD

First Name & Middle Initial & Last Name & Degree

philippe GAIN, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

36309759

Citation

Chiquet C, Vignal C, Gohier P, Heron E, Thuret G, Rougier MB, Lehmann A, Flet L, Quesada JL, Roustit M, Milea D, Pepin JL; ENDOTHELION group. Treatment of nonarteritic anterior ischemic optic neuropathy with an endothelin antagonist: ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy)-a multicentre randomised controlled trial protocol. Trials. 2022 Oct 29;23(1):916. doi: 10.1186/s13063-022-06786-9.

Results Reference

derived

Learn more about this trial

ENDOTHELION Study Group: Effect of Bosentan in NAION Patients

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