Tenecteplase in Central Retinal Artery Occlusion Study (TenCRAOS): Protocol for a randomized-controlled trial

Abstract

Central retinal artery occlusion (CRAO) is an ophthalmologic emergency that, without prompt reperfusion, is associated with a high risk of permanent blindness. There is currently no evidence-based, effective treatment for CRAO. TenCRAOS is an investigator-initiated, international, multicenter, randomized controlled, double-dummy, double-blind, phase III trial testing tenecteplase (TNK) 0.25 mg/kg + placebo versus acetylsalicylic acid (ASA) 300 mg + placebo. The target population is patients diagnosed with CRAO and a best-corrected visual acuity (BCVA) of ⩾1.0 logarithm of the minimum angle of resolution (logMAR), corresponding to a decimal BCVA of ⩽0.1 or a fraction BCVA of ⩽6/60, who can be treated within 4.5 h. Assuming a difference in proportion of participants reaching the primary endpoint of 20% in the placebo/ASA treatment group versus 50% in the TNK/placebo group, we need 78 participants to reach 80% power to detect the difference on a 5% significance level. The primary outcome is the proportion of participants with BCVA of ⩽0.7 logMAR in the affected eye at 30-day follow-up, corresponding to a decimal BCVA of ⩾0.2 or fraction BCVA of ⩾6/30, representing a clinically relevant improvement of BCVA of ⩾0.3 logMAR (or 15 letters). Secondary efficacy outcomes include proportion of participants with BCVA of ⩽0.5 logMAR, corresponding to a decimal BCVA of ⩾0.32 or fraction BCVA of ⩾ 6/19, self-reported vision-targeted health status, quality of life, and modified Rankin Score at 30 and 90 days. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding, and mortality. Exploratory analyses include assessment with optical coherence tomography with angiography and transorbital ultrasound. TenCRAOS intends to assess the efficacy and safety of systemic TNK within 4.5 h of CRAO onset.