ENDOTHELION Study Group: Effect of Bosentan in NAION Patients

NCT ID: NCT02377271

Last Updated: 2022-07-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2025-12-31

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).

Conditions

Ischemic Optic Neuropathy

Study Design

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

Study Groups

Bosentan

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

Group Type: EXPERIMENTAL

bosentan

Intervention Type: DRUG

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

Placebo

placebo drug , twice a day, during eight weeks

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

treatment by bosentan or placebo is randomized

Interventions

bosentan

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

Intervention Type: DRUG

placebo

treatment by bosentan or placebo is randomized

Intervention Type: DRUG

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Grenoble

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christophe Pr CHIQUET, Prof, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Grenoble

Locations

University Hospital of Angers

Angers, , France

Site Status: RECRUITING

University Hospital of Bordeaux

Bordeaux, , France

Site Status: TERMINATED

CHU de Grenoble

Grenoble, , France

Site Status: RECRUITING

University Hospital of Grenoble Michallon

Grenoble, , France

Site Status: RECRUITING

Ophtalmological fondation of Rothschild + Bichat Hospital

Paris, , France

Site Status: RECRUITING

Centre National d'Ophtalmologie XV-XX

Paris, , France

Site Status: RECRUITING

University hospital of Saint-Etienne

Saint-Etienne, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Christophe Pr CHIQUET, Prof, MD, PhD

Role: CONTACT

CChiquet@chu-grenoble.fr

BOUZEID Mayssam, PhD

Role: CONTACT

mbouzeid@chu-grenoble.fr

+33 476766660

Facility Contacts

Philippe GOHIER, MD

Role: primary

phgohier@chu-angers.fr

0241353274

Christophe CHIQUET, MD

Role: primary

CChiquet@chu-grenoble.fr

04 76 76 55 16

Catherine VIGNAL, MD

Role: primary

cvignal@fo-rothschild.fr

0148036222

Catherine VIGNAL, MD

Role: primary

cvignal@club-internet.fr

Philippe GAIN, MD

Role: primary

philippe.gain@univ-st-etienne.fr

0477127793

Claire GUILLEMOT, MD

Role: backup

claire.guillemot@gmail.com

0673169519

References

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.

Reference Type: DERIVED

PMID: 36309759 (View on PubMed)

Other Identifiers

2014-000848-14

Identifier Type: -

Identifier Source: org_study_id