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 (THEIA)

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.

Study Overview

• Status: Completed
• Conditions: Central Retinal Artery Occlusion
• Intervention / Treatment: Drug: Alteplase; Drug: Placebo Oral Tablet; Drug: acetylsalicylic acid; Drug: placebo IV

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Annecy, France
    • CH Annecy Genevois
  • Caen, France
    • CHU Caen
  • Chambéry, France, 73000
    • CH Métropole Savoie
  • La Roche-sur-Yon, France, 85000
    • Chd Vendee
  • La Rochelle, France, 17019
    • CH de la Rochelle
  • Lyon, France
    • CHU
  • Montpellier, France, 34295
    • CHU de Montpellier
  • Nantes, France, 44093
    • CHU de Nantes
  • Nice, France, 06001
    • CHU de Nice
  • Paris, France, 75019
    • Fondation Ophtalmologique Rothschild
  • Perpignan, France
    • CH Perpignan
  • Rennes, France, 35033
    • CHU de Rennes
  • Rouen, France
    • CHU Rouen
  • Saint-Nazaire, France, 44606
    • CH de SAINT NAZAIRE
  • Toulouse, France, 31059
    • CHU de Toulouse
  • Tours, France, 37044
    • CHU de Tours
  • Vannes, France
    • CH Vannes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Benoit GUILLON, Dr, Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2018
• Primary Completion (Actual): January 16, 2024
• Study Completion (Actual): January 16, 2024

Study Registration Dates

• First Submitted: June 20, 2017
• First Submitted That Met QC Criteria: June 22, 2017
• First Posted (Actual): June 23, 2017

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: visual field; visual acuity; Central retinal artery occlusion; mRs; NEI-VFQ-25
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Diseases; Arterial Occlusive Diseases; Retinal Artery Occlusion; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin; Tissue Plasminogen Activator
• Other Study ID Numbers: RC17_0061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No