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

Study Overview
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Brief Summary
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The aim of the THEIA study is to determine if Alteplase administrated within 4.5 hours improve visual deficit due to acute CRAO with a good safety profile.

Official Title
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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

Conditions
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Central Retinal Artery Occlusion

Intervention / Treatment
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* Drug: Alteplase
* Drug: acetylsalicylic acid
* Drug: Placebo Oral Tablet
* Drug: placebo IV


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A : Alteplase<br>Intravenous injection of Alteplase and one tablet of placebo | Drug: Alteplase<br>* 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.<br>* Other names: Actilyse;Drug: Placebo Oral Tablet<br>* One placebo oral tablet which doesn't contain the active ingredient acetyl salicylic acid<br>* Other names: Placebo aspirin;|
| Active Comparator: B : Acetylsalicylic Acid<br>one tablet of Acetylsalicylic Acid and one dose of IV placebo | Drug: acetylsalicylic acid<br>* one tablet of aspirin 300 mg<br>* Other names: Aspirin;Drug: placebo IV<br>* IV saline solution (0.9 %):10 mL in a syringe administered over 1 minute, followed by 50 mL as an infusion over 1 hour<br>* Other names: Placebo Actilyse;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| visual acuity (VA) improvement after treatment | Improvement of the VA is defined by a gain of 15 letters or more on the ETDRS VA chart or ordinal scale | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance | Number, type and grade of severity of adverse drug reactions | 3 months | 
| Proportion of blindness patients after treatment | 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. | 1 month | 
| Visual field | Visual field at 3 months. | 3 months | 
| Time course of VA on ETDRS chart or ordinal scale |  | 3 months | 
| Time-to-treatment administration impact on VA evolution. | Mean VA improvement according to the time between onset of sign and treatment administration | 1 month | 
| Global disability (modified Rankin scale) after treatment |  | 3 months | 
| Quality of life related to vision (NEI-VFQ-25) after treatment |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central retinal artery occlusion, visual acuity, visual field, mRs, NEI-VFQ-25