ENDOTHELION Study Group: Effect of Bosentan in NAION Patients

NCT02377271 | Unknown Phase 3 DMC

• 1 other identifier: 2014-000848-14
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 7

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.

Conditions

Ischemic Optic Neuropathy

Keywords

Bosentan

Outcome Measures

Primary Outcomes (1)

• mean deviation of automated visual field

  Humphrey 30-2 SITA-standard

  3 month

Secondary Outcomes (7)

• visual acuity

  6, 12 and 24 month

• optic nerve fiber layer thickness

  3, 6, 12 and 24 month

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

  3, 6, 12 and 24 month

• inflammatory marker and prepro-endothelin dosing

  3 month

• mean deviation of automated visual field for controlateral eye

  24 month

Study Arms (2)

Bosentan

EXPERIMENTAL

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

Drug: bosentan

Placebo

PLACEBO COMPARATOR

placebo drug , twice a day, during eight weeks

Drug: placebo

Interventions

bosentan DRUG

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

Bosentan

placebo DRUG

treatment by bosentan or placebo is randomized

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (7)

University Hospital of Angers

Angers, 49100, France

RECRUITING

University Hospital of Bordeaux

Bordeaux, 33000, France

TERMINATED

CHU de Grenoble

Grenoble, 38043, France

RECRUITING

University Hospital of Grenoble Michallon

Grenoble, 38043, France

RECRUITING

Ophtalmological fondation of Rothschild + Bichat Hospital

Paris, 75019, France

RECRUITING

Centre National d'Ophtalmologie XV-XX

Paris, France

RECRUITING

University hospital of Saint-Etienne

Saint-Etienne, 42055, France

RECRUITING

Related Publications (1)

• 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.

  PMID: 36309759 DERIVED

MeSH Terms

Conditions

Optic Neuropathy, Ischemic

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Eye Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Christophe Pr CHIQUET, Prof, MD, PhD

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christophe Pr CHIQUET, Prof, MD, PhD

CONTACT

CChiquet@chu-grenoble.fr

BOUZEID Mayssam, PhD

CONTACT

+33 476766660; mbouzeid@chu-grenoble.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2014
• First Posted: March 3, 2015
• Study Start: August 1, 2015
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2025
• Last Updated: July 7, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (7)