Vision loss diagnosed as a Non-arteritic Anterior Ischemic Optic Neuropathy (NAION)

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2010-023586-22-DE
• Date of registration: 23/12/2011
• Prospective Registration: Yes
• Primary sponsor: Bayer AG
• Public title: Vision loss diagnosed as a Non-arteritic Anterior Ischemic Optic Neuropathy (NAION)
• Scientific title: Prospective Case Crossover Study to Assess Whether PDE5 Inhibitor Exposure in Men Increases the Risk for the Development of Non-arteritic Anterior Ischemic Optic Neuropathy (NAION) - Bayer NAION Study
• Date of first enrolment: 08/06/2012
• Target sample size: 284
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023586-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: yes; Other: yes; Other trial design description: prospective Case Cross-Over; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Australia, Canada, Germany, Italy, Mexico, United States

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

Key inclusion & exclusion criteria

Inclusion criteria:
To be enrolled in the study, subjects must meet all of the following criteria:
1. NAION onset within 45 days before entry to the study defined as including all of the following: Note: The time point of onset was changed in amendment 2.
a) Visual field defect consistent with optic neuropathy
b) Relative Afferent Pupillary Defect (RAPD) Subjects without RAPD may be included in the study if: 1) optic neuropathy was present in the non-study eye, preventing an RAPD in the study eye, or 2) an RAPD could not be measured because the subject had a non-study prosthetic eye or postsurgical pupils. Note: The modification of this inclusion criterion is described under amendment 2.
c) Optic disc edema. Subjects without optic disc edema may be included in the study if optic disc edema was documented by another qualified physician after the onset of NAION and before entry into the study. Note: The modification of this inclusion criterion is described under amendment 2.
2. NAION onset definable by the subject within a 2 calendar day window. (If the subject specifies an exact day of onset, the risk period will include that day and the preceding day.)
3. Men who have taken at least 1 dose of PDE5 inhibitor(s) at any time in the 1 year prior to enrollment in the study.
4. Age 40 years or older
5. Ability to complete a phone interview and recall history adequately
6. Documented, signed and dated written Informed Consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 284
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. History of multiple sclerosis (MS) or suggestive for MS (probable or possible MS) or optic neuritis (or any of the following symptoms or signs suggestive of these diagnoses)
a) Pain on motion of the globe within 3 days of loss of vision
b) Marked recovery of field loss and vision
c) Marked delays on visual evoked potential
2. Evidence of temporal arteritis, as indicated by any of the following findings:
a) Positive temporal artery biopsy
b) Jaw claudication or temporal tenderness
c) Polymyalgia rheumatica
d) High ESR (?40 mm/h) platelets (>400 x 109 L), and/or CRP (>10 mg/dL). Subjects with an ESR above 40 mm/hr are allowed to be included if 1) the elevated sedimentation rate could be attributed to some other cause and/or 2) the subject had no other symptoms or indications of temporal arteritis or if temporal arteritis has been excluded by appropriate diagnostic methods. Note: The modification of this exclusion criterion is described under amendment 2.
e) Large cup in fellow eye with a >50% cup to disc ratio
3. History of vasculitis or collagen vascular disease (eg, systemic lupus erythematosus, polyarteritis nodosa), or any other inflammatory disease associated with arteritic anterior ischemic optic neuropathy (AION) or disc swelling
4. Evidence of elevated intracranial pressure
5. Daily dosing of PDE5 inhibitor for benign prostatic hyperplasia and/or pulmonary arterial hypertension.
Opthalmological
1. Any of the following orbital signs
a) Proptosis or resistance to retropulsion which may be associated with Graves eye disease or Graves-related exophthalmos
b) Arterialized conjunctival vessels
c) Choroidal folds
d) Orbital mass
2. Ocular inflammation that may be associated with any of the following conditions:
a) Iritis or vitritis
b) Evidence of active sarcoidosis
c) Evidence of active syphilis
3. Acute glaucoma or intraocular pressure (IOP) ?30 mmHg
4. Retinal vein occlusion
5. Previous history of NAION
6. Retinal detachment
7. Uveitis
8. Lens opacities (which prevent an adequate examination)
9. Use of any drugs known to affect the optic nerve or retina that cannot be excluded



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Eye Diseases [C11]

Non-arteritic Anterior Ischemic Optic Neuropathy (NAION)

Intervention(s)

Pharmaceutical Form:
INN or Proposed INN: VARDENAFIL
CAS Number: 224785-90-4
INN or Proposed INN: SILDENAFIL
CAS Number: 139755-83-2
INN or Proposed INN: TADALAFIL
CAS Number: 171596-29-5
INN or Proposed INN: AVANAFIL
CAS Number: 330784-47-9

Primary Outcome(s)

Primary end point(s): The primary study variable is the relative risk (as measured by the HR) of NAION, contrasting PDE5 inhibitor exposure in the risk period with PDE5 inhibitor exposure during the control periods for each NAION case.
Any additional safety information provided by the subject will be collected through the medical history taken at Visit 1 and any adverse events reported at Visit 2.

Timepoint(s) of evaluation of this end point: Subjects will be assessed at 2 visits, as summarized in the Study Flow Chart (Appendix 10.1). Visit 1 (Day 1) will include screening, confirmation of the diagnosis of NAION (with date and time of onset), enrollment, and collection of data on PDE5 inhibitor and other concomitant medication use. Visit 2 (Day 90) will be a follow-up visit to document the persistence of vision loss and confirm the diagnosis of NAION.

Main Objective: To determine whether the use of PDE5 inhibitors (vardenafil, sildenafil, tadalafil or avanafil) increases the risk for the development of NAION.

Secondary Objective: None

Secondary ID(s)

BAY38-9456/12912

Source(s) of Monetary Support

Bayer AG

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 17/03/2019
• Date Completed: 28/03/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-023586-22/results