A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion

Stephen J Ryan; Øystein Kalsnes Jørstad; Mona Skjelland; Maiju Pesonen; Claus Z Simonsen; Toke Bek; Rolf Ankerlund Blauenfeldt; Petra Ijäs; Arja Laitinen; Andrej Khanevski; Jørgen Krohn; Eyvind Rødahl; Robin Lemmens; Jelle Demeestere; Catherine Cassiman; Ingvild Nakstad; Kristin Evensen; Tiril Sandell; Steffen Hamann; Thomas C Truelsen; Louisa M Christensen; Sverre Rosenbaum; Vaidas Matijošaitis; Reda Žemaitienė; Hanne Ellekjær; Erlend Almaas; Dordi Austeng; Michael V Mazya; Frank Traïsk; Pauli Ylikotila; Ulpu Salmi; Kristian N Jenssen; Håvard Lisether; Cathrine Breivik; Kristina Devik; Lasse-Marius Elden Honningsvåg; Jurgita Valaikienė; Andrius Cimbalas; Vetle Nilsen Malmberg; Espen Anderson; Ansar Roy; Thor Håkon Skattør; Kristian Lundsgaard Kraglund; Christina Kefaloykos; Inge Christoffer Olsen; Peter Vanacker; Daniel Strbian; Morten C Moe; Anne Hege Aamodt; TenCRAOS Investigators

doi:10.1056/NEJMoa2508515

A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion

Stephen J Ryan, Øystein Kalsnes Jørstad, Mona Skjelland, Maiju Pesonen, Claus Z Simonsen, Toke Bek, Rolf Ankerlund Blauenfeldt, Petra Ijäs, Arja Laitinen, Andrej Khanevski, Jørgen Krohn, Eyvind Rødahl, Robin Lemmens, Jelle Demeestere, Catherine Cassiman, Ingvild Nakstad, Kristin Evensen, Tiril Sandell, Steffen Hamann, Thomas C TruelsenLouisa M Christensen, Sverre Rosenbaum, Vaidas Matijošaitis, Reda Žemaitienė, Hanne Ellekjær, Erlend Almaas, Dordi Austeng, Michael V Mazya, Frank Traïsk, Pauli Ylikotila, Ulpu Salmi, Kristian N Jenssen, Håvard Lisether, Cathrine Breivik, Kristina Devik, Lasse-Marius Elden Honningsvåg, Jurgita Valaikienė, Andrius Cimbalas, Vetle Nilsen Malmberg, Espen Anderson, Ansar Roy, Thor Håkon Skattør, Kristian Lundsgaard Kraglund, Christina Kefaloykos, Inge Christoffer Olsen, Peter Vanacker, Daniel Strbian, Morten C Moe, Anne Hege Aamodt^*, TenCRAOS Investigators

^*Corresponding author af dette arbejde

2 Citationer (Scopus)

Abstract

BACKGROUND: Central retinal artery occlusion can result in permanent vision loss. Effective treatment is lacking.

METHODS: We conducted a phase 3, double-blind, double-dummy, randomized, controlled trial involving adults with acute, nonarteritic central retinal artery occlusion who had symptom onset within 4.5 hours before treatment. Patients were assigned, in a 1:1 ratio, to receive intravenous tenecteplase (at a dose of 0.25 mg per kilogram of body weight) and oral placebo or intravenous placebo and oral aspirin (at a dose of 300 mg). The primary end point was vision recovery, defined as a best corrected visual acuity (BCVA) in the affected eye at 30 days of up to 0.7 logMAR (logarithm of the minimum angle of resolution; equivalent to ≥20/100). Key secondary visual end points were a BCVA of up to 0.5 logMAR (equivalent to ≥20/63), mean improvement in BCVA, and perimetry score at 30 days. Key safety end points included symptomatic intracranial hemorrhage, major bleeding, and death.

RESULTS: A total of 78 patients at 16 sites in six countries underwent randomization, with 40 assigned to receive tenecteplase and 38 to receive aspirin. At 30 days, 8 patients (20%) in the tenecteplase group and 9 patients (24%) in the aspirin group had vision recovery (risk difference, -3.7 percentage points; 95% confidence interval, -22.0 to 14.7; P = 0.69). The outcomes with regard to the secondary visual end points did not differ substantially between the groups. There was a greater incidence of adverse events in the tenecteplase group, including one fatal intracranial hemorrhage.

CONCLUSIONS: Intravenous tenecteplase administered within 4.5 hours after onset of central retinal artery occlusion did not result in significantly greater vision recovery at 30 days than oral aspirin but was associated with serious safety concerns. (Funded by Oslo University Hospital and others; TenCRAOS ClinicalTrials.gov number, NCT04526951; EU Clinical Trials number, 2024-517606-29-00.).

Originalsprog	Engelsk
Tidsskrift	The New England journal of medicine
Vol/bind	394
Udgave nummer	5
Sider (fra-til)	442-450
Antal sider	9
ISSN	0028-4793
DOI	https://doi.org/10.1056/NEJMoa2508515
Status	Udgivet - 29 jan. 2026

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Ryan, S. J., Jørstad, Ø. K., Skjelland, M., Pesonen, M., Simonsen, C. Z., Bek, T., Blauenfeldt, R. A., Ijäs, P., Laitinen, A., Khanevski, A., Krohn, J., Rødahl, E., Lemmens, R., Demeestere, J., Cassiman, C., Nakstad, I., Evensen, K., Sandell, T., Hamann, S., ... TenCRAOS Investigators (2026). A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion. The New England journal of medicine, 394(5), 442-450. https://doi.org/10.1056/NEJMoa2508515

Ryan, SJ, Jørstad, ØK, Skjelland, M, Pesonen, M, Simonsen, CZ, Bek, T, Blauenfeldt, RA, Ijäs, P, Laitinen, A, Khanevski, A, Krohn, J, Rødahl, E, Lemmens, R, Demeestere, J, Cassiman, C, Nakstad, I, Evensen, K, Sandell, T, Hamann, S , Truelsen, TC , Christensen, LM , Rosenbaum, S, Matijošaitis, V, Žemaitienė, R, Ellekjær, H, Almaas, E, Austeng, D, Mazya, MV, Traïsk, F, Ylikotila, P, Salmi, U, Jenssen, KN, Lisether, H, Breivik, C, Devik, K, Honningsvåg, L-ME, Valaikienė, J, Cimbalas, A, Malmberg, VN, Anderson, E, Roy, A, Skattør, TH, Kraglund, KL, Kefaloykos, C, Olsen, IC, Vanacker, P, Strbian, D, Moe, MC, Aamodt, AH & TenCRAOS Investigators 2026, 'A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion', The New England journal of medicine, bind 394, nr. 5, s. 442-450. https://doi.org/10.1056/NEJMoa2508515

@article{bc5b7d7e64604351900f701a9070ceb5,

title = "A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion",

abstract = "BACKGROUND: Central retinal artery occlusion can result in permanent vision loss. Effective treatment is lacking.METHODS: We conducted a phase 3, double-blind, double-dummy, randomized, controlled trial involving adults with acute, nonarteritic central retinal artery occlusion who had symptom onset within 4.5 hours before treatment. Patients were assigned, in a 1:1 ratio, to receive intravenous tenecteplase (at a dose of 0.25 mg per kilogram of body weight) and oral placebo or intravenous placebo and oral aspirin (at a dose of 300 mg). The primary end point was vision recovery, defined as a best corrected visual acuity (BCVA) in the affected eye at 30 days of up to 0.7 logMAR (logarithm of the minimum angle of resolution; equivalent to ≥20/100). Key secondary visual end points were a BCVA of up to 0.5 logMAR (equivalent to ≥20/63), mean improvement in BCVA, and perimetry score at 30 days. Key safety end points included symptomatic intracranial hemorrhage, major bleeding, and death.RESULTS: A total of 78 patients at 16 sites in six countries underwent randomization, with 40 assigned to receive tenecteplase and 38 to receive aspirin. At 30 days, 8 patients (20\%) in the tenecteplase group and 9 patients (24\%) in the aspirin group had vision recovery (risk difference, -3.7 percentage points; 95\% confidence interval, -22.0 to 14.7; P = 0.69). The outcomes with regard to the secondary visual end points did not differ substantially between the groups. There was a greater incidence of adverse events in the tenecteplase group, including one fatal intracranial hemorrhage.CONCLUSIONS: Intravenous tenecteplase administered within 4.5 hours after onset of central retinal artery occlusion did not result in significantly greater vision recovery at 30 days than oral aspirin but was associated with serious safety concerns. (Funded by Oslo University Hospital and others; TenCRAOS ClinicalTrials.gov number, NCT04526951; EU Clinical Trials number, 2024-517606-29-00.).",

keywords = "Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Acute Disease/therapy, Administration, Intravenous, Administration, Oral, Aspirin/administration \& dosage, Double-Blind Method, Fibrinolytic Agents/administration \& dosage, Intracranial Hemorrhages/chemically induced, Retinal Artery Occlusion/drug therapy, Tenecteplase/administration \& dosage, Visual Acuity/drug effects, Recovery of Function/drug effects, Incidence, Prospective Studies, Treatment Outcome",

author = "Ryan, \{Stephen J\} and J{\o}rstad, \{{\O}ystein Kalsnes\} and Mona Skjelland and Maiju Pesonen and Simonsen, \{Claus Z\} and Toke Bek and Blauenfeldt, \{Rolf Ankerlund\} and Petra Ij{\"a}s and Arja Laitinen and Andrej Khanevski and J{\o}rgen Krohn and Eyvind R{\o}dahl and Robin Lemmens and Jelle Demeestere and Catherine Cassiman and Ingvild Nakstad and Kristin Evensen and Tiril Sandell and Steffen Hamann and Truelsen, \{Thomas C\} and Christensen, \{Louisa M\} and Sverre Rosenbaum and Vaidas Matijo{\v s}aitis and Reda {\v Z}emaitienė and Hanne Ellekj{\ae}r and Erlend Almaas and Dordi Austeng and Mazya, \{Michael V\} and Frank Tra{\"i}sk and Pauli Ylikotila and Ulpu Salmi and Jenssen, \{Kristian N\} and H{\aa}vard Lisether and Cathrine Breivik and Kristina Devik and Honningsv{\aa}g, \{Lasse-Marius Elden\} and Jurgita Valaikienė and Andrius Cimbalas and Malmberg, \{Vetle Nilsen\} and Espen Anderson and Ansar Roy and Skatt{\o}r, \{Thor H{\aa}kon\} and Kraglund, \{Kristian Lundsgaard\} and Christina Kefaloykos and Olsen, \{Inge Christoffer\} and Peter Vanacker and Daniel Strbian and Moe, \{Morten C\} and Aamodt, \{Anne Hege\} and \{TenCRAOS Investigators\}",

note = "Copyright {\textcopyright} 2026 Massachusetts Medical Society.",

year = "2026",

month = jan,

day = "29",

doi = "10.1056/NEJMoa2508515",

language = "English",

volume = "394",

pages = "442--450",

journal = "The New England journal of medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "5",

}

TY - JOUR

T1 - A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion

AU - Ryan, Stephen J

AU - Jørstad, Øystein Kalsnes

AU - Skjelland, Mona

AU - Pesonen, Maiju

AU - Simonsen, Claus Z

AU - Bek, Toke

AU - Blauenfeldt, Rolf Ankerlund

AU - Ijäs, Petra

AU - Laitinen, Arja

AU - Khanevski, Andrej

AU - Krohn, Jørgen

AU - Rødahl, Eyvind

AU - Lemmens, Robin

AU - Demeestere, Jelle

AU - Cassiman, Catherine

AU - Nakstad, Ingvild

AU - Evensen, Kristin

AU - Sandell, Tiril

AU - Hamann, Steffen

AU - Truelsen, Thomas C

AU - Christensen, Louisa M

AU - Rosenbaum, Sverre

AU - Matijošaitis, Vaidas

AU - Žemaitienė, Reda

AU - Ellekjær, Hanne

AU - Almaas, Erlend

AU - Austeng, Dordi

AU - Mazya, Michael V

AU - Traïsk, Frank

AU - Ylikotila, Pauli

AU - Salmi, Ulpu

AU - Jenssen, Kristian N

AU - Lisether, Håvard

AU - Breivik, Cathrine

AU - Devik, Kristina

AU - Honningsvåg, Lasse-Marius Elden

AU - Valaikienė, Jurgita

AU - Cimbalas, Andrius

AU - Malmberg, Vetle Nilsen

AU - Anderson, Espen

AU - Roy, Ansar

AU - Skattør, Thor Håkon

AU - Kraglund, Kristian Lundsgaard

AU - Kefaloykos, Christina

AU - Olsen, Inge Christoffer

AU - Vanacker, Peter

AU - Strbian, Daniel

AU - Moe, Morten C

AU - Aamodt, Anne Hege

AU - TenCRAOS Investigators

PY - 2026/1/29

Y1 - 2026/1/29

N2 - BACKGROUND: Central retinal artery occlusion can result in permanent vision loss. Effective treatment is lacking.METHODS: We conducted a phase 3, double-blind, double-dummy, randomized, controlled trial involving adults with acute, nonarteritic central retinal artery occlusion who had symptom onset within 4.5 hours before treatment. Patients were assigned, in a 1:1 ratio, to receive intravenous tenecteplase (at a dose of 0.25 mg per kilogram of body weight) and oral placebo or intravenous placebo and oral aspirin (at a dose of 300 mg). The primary end point was vision recovery, defined as a best corrected visual acuity (BCVA) in the affected eye at 30 days of up to 0.7 logMAR (logarithm of the minimum angle of resolution; equivalent to ≥20/100). Key secondary visual end points were a BCVA of up to 0.5 logMAR (equivalent to ≥20/63), mean improvement in BCVA, and perimetry score at 30 days. Key safety end points included symptomatic intracranial hemorrhage, major bleeding, and death.RESULTS: A total of 78 patients at 16 sites in six countries underwent randomization, with 40 assigned to receive tenecteplase and 38 to receive aspirin. At 30 days, 8 patients (20%) in the tenecteplase group and 9 patients (24%) in the aspirin group had vision recovery (risk difference, -3.7 percentage points; 95% confidence interval, -22.0 to 14.7; P = 0.69). The outcomes with regard to the secondary visual end points did not differ substantially between the groups. There was a greater incidence of adverse events in the tenecteplase group, including one fatal intracranial hemorrhage.CONCLUSIONS: Intravenous tenecteplase administered within 4.5 hours after onset of central retinal artery occlusion did not result in significantly greater vision recovery at 30 days than oral aspirin but was associated with serious safety concerns. (Funded by Oslo University Hospital and others; TenCRAOS ClinicalTrials.gov number, NCT04526951; EU Clinical Trials number, 2024-517606-29-00.).

AB - BACKGROUND: Central retinal artery occlusion can result in permanent vision loss. Effective treatment is lacking.METHODS: We conducted a phase 3, double-blind, double-dummy, randomized, controlled trial involving adults with acute, nonarteritic central retinal artery occlusion who had symptom onset within 4.5 hours before treatment. Patients were assigned, in a 1:1 ratio, to receive intravenous tenecteplase (at a dose of 0.25 mg per kilogram of body weight) and oral placebo or intravenous placebo and oral aspirin (at a dose of 300 mg). The primary end point was vision recovery, defined as a best corrected visual acuity (BCVA) in the affected eye at 30 days of up to 0.7 logMAR (logarithm of the minimum angle of resolution; equivalent to ≥20/100). Key secondary visual end points were a BCVA of up to 0.5 logMAR (equivalent to ≥20/63), mean improvement in BCVA, and perimetry score at 30 days. Key safety end points included symptomatic intracranial hemorrhage, major bleeding, and death.RESULTS: A total of 78 patients at 16 sites in six countries underwent randomization, with 40 assigned to receive tenecteplase and 38 to receive aspirin. At 30 days, 8 patients (20%) in the tenecteplase group and 9 patients (24%) in the aspirin group had vision recovery (risk difference, -3.7 percentage points; 95% confidence interval, -22.0 to 14.7; P = 0.69). The outcomes with regard to the secondary visual end points did not differ substantially between the groups. There was a greater incidence of adverse events in the tenecteplase group, including one fatal intracranial hemorrhage.CONCLUSIONS: Intravenous tenecteplase administered within 4.5 hours after onset of central retinal artery occlusion did not result in significantly greater vision recovery at 30 days than oral aspirin but was associated with serious safety concerns. (Funded by Oslo University Hospital and others; TenCRAOS ClinicalTrials.gov number, NCT04526951; EU Clinical Trials number, 2024-517606-29-00.).

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Acute Disease/therapy

KW - Administration, Intravenous

KW - Administration, Oral

KW - Aspirin/administration & dosage

KW - Double-Blind Method

KW - Fibrinolytic Agents/administration & dosage

KW - Intracranial Hemorrhages/chemically induced

KW - Retinal Artery Occlusion/drug therapy

KW - Tenecteplase/administration & dosage

KW - Visual Acuity/drug effects

KW - Recovery of Function/drug effects

KW - Incidence

KW - Prospective Studies

KW - Treatment Outcome

UR - https://www.scopus.com/pages/publications/105028929153

U2 - 10.1056/NEJMoa2508515

DO - 10.1056/NEJMoa2508515

M3 - Journal article

C2 - 41604638

SN - 0028-4793

VL - 394

SP - 442

EP - 450

JO - The New England journal of medicine

JF - The New England journal of medicine

IS - 5

ER -

A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion

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