A Phase III Randomized, Blind, Double Dummy, Multicenter Study Assessing the Efficacy and Safety of IV THrombolysis (Alteplase) in Patients With acutE Central retInal Artery Occlusion

• Alteplase (Drug), also known as Actilyse: alteplase administered as an intravenous infusion (0.9 mg/kg; maximum dose 90 mg): 10% given as an IV bolus, followed immediately by the remaining given as an IV infusion over 1 hour.
• acetylsalicylic acid (Drug), also known as Aspirin: one tablet of aspirin 300 mg
• Placebo Oral Tablet (Drug), also known as Placebo aspirin: One placebo oral tablet which doesn't contain the active ingredient acetyl salicylic acid
• placebo IV (Drug), also known as Placebo Actilyse: IV saline solution (0.9 %):10 mL in a syringe administered over 1 minute, followed by 50 mL as an infusion over 1 hour

Primary outcomes

• visual acuity (VA) improvement after treatment [1 month]: Improvement of the VA is defined by a gain of 15 letters or more on the ETDRS VA chart or ordinal scale

Secondary outcomes

• Tolerance [3 months]: Number, type and grade of severity of adverse drug reactions
• Proportion of blindness patients after treatment [1 month]: Blindness is defined according to WHO revised categories of visual impairment, as VA < 1/20 (< 20/400 or > 1.3 log.MAR) or visual field < 10.
• Visual field [3 months]: Visual field at 3 months.
• Time course of VA on ETDRS chart or ordinal scale [3 months]
• Time-to-treatment administration impact on VA evolution. [1 month]: Mean VA improvement according to the time between onset of sign and treatment administration
• Global disability (modified Rankin scale) after treatment [3 months]
• Quality of life related to vision (NEI-VFQ-25) after treatment [3 months]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patients aged up to 18 years
* CRAO diagnosis by fundoscopic examination or non-mydriatic retinophotography (NMR) performed by an ophthalmologist.
* Blindness defined according to WHO classification as visual acuity <1/20 (20/400).
* Treatment intervention should be initiated by a stroke team as quickly as possible and within 4.5 hours from symptom onset.
* No clinical (e.g headache with jaw claudication or scalp tenderness, no temporal pulse) or laboratory evidence (elevated CRP) of giant cell arteritis
* No clinical or radiological evidence of stroke within the last 3 months.
* Patients covered by health care insurance (social security)
* Written informed consent obtained.

Exclusion Criteria:

* Symptoms onset more than 4.5 h prior to infusion start or undetermined time of symptom onset.
* Minor VA deficit or VA rapidly improving before start of infusion.
* CRAO without foveal ischemia.
* Other retinal vascular disease: occlusion of branch of the CRA without significant VA loss, occlusion of the retinal vein, proliferative diabetic retinopathy or any other severe retinopathy.
* Clinical or laboratory evidence of temporal arteritis.
* Evidence of ICH or ischemic stroke on the pre-administration CT scan or MRI.
* Pregnant or lactating women
* Minors
* Adults under guardianship or trusteeship
* Any contraindication to alteplase
* Any contraindication to aspirin

• Results publication: Preterre C, Gaultier A, Obadia M, Vignal C, Mourand I, Plat J, Sablot D, Gaudron M, Rodier G, Godeneche G, Urbanczyk C, Marc G, Massardier E, Adam S, Boulanger M, Marcel S, Mechtouff L, Ronziere T, Calviere L, Godard-Ducceschi S, Barbin L, Lebranchu P, Guillon B; THEIA collaborators. Intravenous alteplase versus oral aspirin for acute central retinal artery occlusion within 4.5 h of severe vision loss (THEIA): a multicentre, double-dummy, patient-blinded and assessor-blinded, randomised, controlled, phase 3 trial. Lancet Neurol. 2025 Nov;24(11):909-919. doi: 10.1016/S1474-4422(25)00308-4. PMID 41109232
• Results publication: Abdelmassih Y, Mauget-Faysse M, Seners P, Milea D, Hallali G, Guillaume J, Lecler A, Vignal C, Le Mer Y, Paques M, Bonnin S, Obadia M. Early reperfusion in patients with acute retinal artery occlusion: A multicenter prospective study. Int J Stroke. 2025 Mar;20(3):338-346. doi: 10.1177/17474930241306692. Epub 2024 Dec 24. PMID 39614619

• Benoit GUILLON, Dr, Principal investigator, Nantes University Hospital