Clinical trial NCT02377271: ENDOTHELION Study Group: Effect of Bosentan in NAION Patients
Official title: Effect of Bosentan in Patients With Non Arteritic Ischemic Optic Neuropathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ischemic Optic Neuropathy
Keywords: Bosentan
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2015-03-03
Enrollment: 86
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: mean deviation of automated visual field
timeFrame: 3 month
Secondary outcomes:
measure: visual acuity
timeFrame: 6, 12 and 24 month
measure: optic nerve fiber layer thickness
timeFrame: 3, 6, 12 and 24 month
measure: mean deviation of automated visual field for healthy eye and NAION eye
timeFrame: 3, 6, 12 and 24 month
measure: inflammatory marker and prepro-endothelin dosing
timeFrame: 3 month
measure: mean deviation of automated visual field for controlateral eye
timeFrame: 24 month
measure: VFQ-25 score
timeFrame: 3 and 12 month
measure: rate of bilateral occurence of NAION
timeFrame: at 24 month visit
Other outcomes:
Locations:
city: Angers
country: France
facility: University Hospital of Angers
city: Bordeaux
country: France
facility: University Hospital of Bordeaux
city: Grenoble
country: France
facility: CHU de Grenoble
city: Grenoble
country: France
facility: University Hospital of Grenoble Michallon
city: Paris
country: France
facility: Ophtalmological fondation of Rothschild + Bichat Hospital
city: Paris
country: France
facility: Centre National d'Ophtalmologie XV-XX
city: Saint-Etienne
country: France
facility: University hospital of Saint-Etienne
Study officials:
affiliation: University Hospital, Grenoble
name: Christophe Pr CHIQUET, Prof, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.