Evaluation of the effects of bosentan in the management of patients in the acute phase of acute anterior ischemic optic neuropathy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Grenoble Alpes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

31 Jul 2015 → ongoing

Decision date (initial)

2024-10-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

PHRCI 2012 / Fondation Visio / APMC

External identifiers

EU CT number

2024-518345-21-00

EudraCT number

2014-000848-14

ClinicalTrials.gov

NCT02377271

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluate at 3 MONTHS the effect on visual field (mean deficit) of bosentan 250 mg daily for 2 months (versus placebo) in early non-arteritic acute anterior ischemic optic neuropathy (NOIAA).

Secondary objectives 4

1. assess visual acuity at 3 months
2. anatomical (OCT) and functional (visual acuity, visual field) assessment at 6, 12 and 24 months
3. compare the evolution of endothelial function, atherosclerosis and inflammation markers under treatment with bosentan 250 mg daily
4. evaluate the nycthemeral blood pressure profile of NOIAA subjects

Conditions and MedDRA coding

early stage of acute non-arteritic anterior ischemic optic neuropathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Men or women aged 50 or over
2. Negative pregnancy test and use of effective contraception for the duration of the study for non-menopausal women
3. Patients who have signed the consent form
4. Patients affiliated with or benefiting from a social security scheme
5. Patients with systolic blood pressure greater than or equal to 100 mmHg.
6. The diagnosis of NOIAA is made in the presence of recent onset (less than or equal to 21 days) of an alteration of the visual field, whether or not associated with a rapidly progressive or abrupt painless drop in visual acuity and/or, AND associated with diffuse or sectorial, pale/white papilledema, sometimes with peripapillary hemorrhages. the diagnosis of Horton's disease should be ruled out

Exclusion criteria 21

1. Pregnant women, parturients and nursing mothers
2. Women of childbearing age using only hormonal contraception (including oral, injectable, implantable or trans-dermal contraceptives)
3. Patients with other acute or chronic intercurrent ocular pathology interfering with visual acuity or visual field (diabetic, 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)
4. Simultaneous bilateral NOIAA, 1 month or less apart
5. Signs that may raise suspicion of another inflammatory neuropathy: arterial NOIAA (Horton's disease), pain on mobilization of the globe or any sign suggestive of optic neuritis, known diagnosis of MS, history of inflammatory optic neuropathy (homo or ipsi-lateral). A temporal artery biopsy will be performed in the presence of symptoms suggestive of Horton's disease, or in the presence of pale and/or diffuse edema, or associated obliteration of the central retinal artery.
6. Signs suggestive of retinal pathology
7. Signs suggestive of neuroretinitis or other optic neuropathy. Any atypia will require brain imaging (MRI).
8. Patients with systolic blood pressure below 100 mmHg
9. Patients with orthostatic arterial hypotension (20 mmHg drop in SAP and/or 10 mmHg drop in DBP when moving to a standing position)
10. Neurological history of vascular or tumoral origin that may alter the visual field or lead to optic neuropathy
11. Systemic inflammatory pathology
12. Known allergy to bosentan
13. Patients with moderate to severe hepatic impairment (Child-Pugh class B or C), biliary cirrhosis and cholestasis (serum levels of hepatic aminotransferases, aspartate aminotransferases (ASAT) and/or alanine aminotransferases (ALAT), greater than 3 times the upper limit of normal, bilirubin greater than 2 times normal)
14. Estimated glomerular filtration rate (GFR) < 30 ml/min/1.73 m2
15. Patients treated with drugs whose efficacy may be reduced by activation of cytochrome P450, 2C9, 3A4 and 2C19 isoenzymes
16. Patients treated with cordarone® (amiodarone)
17. - Patients treated with one of the treatments prohibited in the study (paragraph 5.5)
18. Patients treated with systemic corticosteroids (background treatment or treatment initiated at the time of NOIAA diagnosis)
19. Person deprived of liberty by judicial or administrative decision, legally protected adult, hospitalized person
20. Ongoing participation in another clinical research study or exclusion period from another clinical study
21. Person under legal protection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Average deficit (in decibels) in automated visual field 30/2

Secondary endpoints 8

1. the thickness of the optic fiber layer in SD OCT of the affected eye
2. visual acuity (ETDRS scale) and visual field parameters
3. evaluation of the following inflammation biomarkers: RANTES, MCP-1, TNF-, INF-γ, IL-6, IL-10 and TGF
4. daytime and nighttime blood pressure values and variations at Baseline
5. automated visual field (mean deviation in Humphrey 30-2 and 60-4 sita-standard test, in dB) for healthy eye and NOIAA eye
6. plasma assay for prepro-endothelin
7. rate of bilateralization of the contralateral eye (occurrence of NOIAA) at 24 months
8. quality of life questionnaire (French version of VFQ-25)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Grenoble Alpes

Sponsor organisation

Centre Hospitalier Universitaire Grenoble Alpes

Address

Boulevard De La Chantourne, Cs 10217, La Tronche Cs 10217 La Tronche

City

Grenoble Cedex 9

Postcode

38043

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Grenoble Alpes

Contact name

Christophe

Public contact point

Organisation

Centre Hospitalier Universitaire Grenoble Alpes

Contact name

Christophe

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications