ENDOTHELION Study Group: Effect of Bosentan in NAION Patients

Phase 3

Recruiting

• Conditions: Ischemic Optic Neuropathy
• Interventions: Drug: placebo; Drug: bosentan

• Registration Number: NCT02377271
• Lead Sponsor: University Hospital, Grenoble

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).

Study Timeline

• Study First Submitted: 2014-12-05
• Study First Submitted QC: 2015-02-24
• Study First Posted: 2015-03-03
• Study Start: 2015-08
• Status Verified: 2022-04
• Last Update Submitted: 2022-07-04
• Last Update Posted: 2022-07-07
• Primary Completion: 2023-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 86

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	placebo drug , twice a day, during eight weeks
Bosentan	bosentan	Bosentan at a dose of 125 mg two times daily, will be administered orally, twice a day, during eight weeks

Primary Outcome Measures

Name	Time	Method
mean deviation of automated visual field	3 month	Humphrey 30-2 SITA-standard

Secondary Outcome Measures

Name	Time	Method
visual acuity	6, 12 and 24 month	ETDRS scale
mean deviation of automated visual field for healthy eye and NAION eye	3, 6, 12 and 24 month	Humphrey 30-2
inflammatory marker and prepro-endothelin dosing	3 month	RANTES, MCP-1, TNF-α, INF-γ, IL-6, IL-10 and TGF-β
optic nerve fiber layer thickness	3, 6, 12 and 24 month	OCT measurement
VFQ-25 score	3 and 12 month	VFQ-25 quality of life
rate of bilateral occurence of NAION	at 24 month visit	rate of bilateralization
mean deviation of automated visual field for controlateral eye	24 month	Humphrey 30-2 sita-standard

Trial Locations

Locations (7)

Centre National d'Ophtalmologie XV-XX; 🇫🇷 Paris, France

University hospital of Saint-Etienne; 🇫🇷 Saint-Etienne, France

University Hospital of Grenoble Michallon; 🇫🇷 Grenoble, France

University Hospital of Angers; 🇫🇷 Angers, France

University Hospital of Bordeaux; 🇫🇷 Bordeaux, France

CHU de Grenoble; 🇫🇷 Grenoble, France

Ophtalmological fondation of Rothschild + Bichat Hospital; 🇫🇷 Paris, France