TENecteplase in Central Retinal Artery Occlusion Stuy (TenCRAOS)

NCT04526951 | Completed Phase 3 DMC

• 4 other identifiers: Oslo UH2018-002546-362019/3272024-517606-29-00
• Study Type: interventional
• Target: 81
• Locations: 6 countries
• Sites: 18

Brief Summary

TENecteplase in Central Retinal Artery Occlusion (TenCRAOS): A Prospective, randomized-controlled, double-dummy, double-blind phase 3 multi-centre trial of TNK 0.25 mg/kg + placebo vs. ASA + placebo (2 arms with 1:1 block randomization). A Prospective, randomized-controlled, double-dummy, double-blind phase 3 multi-centre trial of TNK 0.25 mg/kg + placebo vs. ASA + placebo (2 arms with 1:1 block randomization). At all participating centers, ophthalmologists are involved in the diagnosis and visual outcome measurements using a standardized protocol. The patients will be promptly examined by the ophthalmologist. As soon as the CRAO is diagnosed by the ophthalmologist, the patients will be managed in the stroke unit during treatment, monitoring, and medical investigations. After treatment in the stroke unit, the patients will be re-examined by an ophthalmologist and a neurologist as an out-patient at (30 ±5) and 90 (±15) days

Conditions

Central Retinal Artery Occlusion

Keywords

thrombolysis tenecteplase

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with ≤ 0.7 logMAR visual acuity in the affected eye at 30 (±5) days after treatment, representing an improvement in visual acuity of at least 0.3 logMAR (intention-to-treat (ITT) analysis).

  logMAR

  30 (±5) days

Secondary Outcomes (10)

• Proportion of patients with ≤ 0.5 logMAR visual acuity in the affected eye at 30 (±5) and 90 (±15) days.

  30 (±5) and 90 (±15) days

• Mean improvement in logMAR visual acuity in the affected eye from baseline to 30 (±5) and 90 (±15) days.

  30 (±5) and 90 (±15) days

• Proportion of patients with visual recovery (logMAR ≤ 0.7) and (logMAR ≤ 0.5) in the affected eye 30 (±5) and 90 (±15) days in patients who were treated with tenecteplase within 3 hours of onset

  30 (±5) and 90 (±15) days

• Number of test points seen (of 100) on monocular Esterman perimetry at 30 (±5) and 90 (±15) days

  30 (±5) and 90 (±15) days

• Acute ischemic lesions on follow-up on diffusion-weighted (DWI) MRI or on brain CT at baseline and 24hrs.

  24 hours

Other Outcomes (9)

• All-cause and stroke-related death at discharge, 30 (±5) and 90 (±15) days.

  Discharge assessed up to 7 days , 30 (±5) and 90 (±15) days

• Proportion of patients with any intracranial haemorrhage at 24 hrs

  24 hours

• Proportion of patients with symptomatic intracranial haemorrhage until discharge.

  at discharge, assessed up to 7 days

Study Arms (2)

Tenecteplase

ACTIVE COMPARATOR

The total dose of tenecteplase is 0.25 mg/kg body weight, maximum 25 mg. The total dose will be given as an intravenous bolus

Drug: Intravenous injection of Tenecteplase and one dose of placebo tablet

acetylsalicylic acid

ACTIVE COMPARATOR

one tablet of aspirin 300 mg Other Name: Aspirin

Drug: One tablet of Acetylsalicylic Acid and one dose of IV placebo

Interventions

Intravenous injection of Tenecteplase and one dose of placebo tablet DRUG

Drug: Tenecteplase Tenecteplase administered as an intravenous injection (0.25 mg/kg body weigh; maximum 25 mg)

Also known as: Metalyse

Tenecteplase

One tablet of Acetylsalicylic Acid and one dose of IV placebo DRUG

300 mg Acetylsalisylic acid

Also known as: Aspirin

acetylsalicylic acid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Non-arteritic central retinal artery occlusion with ≥ 1.0 logMAR visual acuitiy and symptoms lasting less than 4.5 hours.
• Ability to administer the Investigator Medicinal Product (IMP) within 4.5 hours of symptom onset.
• Age ≥18 years.
• Informed written consent of the patient.
• A woman of childbearing potential (WOCBP) must confirm that in her opinion, she cannot be pregnant, OR if there is a possibility that she is pregnant, a negative pregnancy test must be confirmed before any IMP is given.

You may not qualify if:

• Other active intervention targeting CRAO.
• Branch retinal artery occlusion, cilioretinal artery supplying the macula, combined arterial-venous occlusion, proliferative diabetic retinopathy, elevated intraocular pressure (\> 30 mmHg) or clinical suspicion of ophthalmic artery occlusion occlusion (e.g. choroidal nonperfusion, absence of cherry red spot, no light perception).
• Systemic diseases; severe general diseases, systemic arterial hypertension (blood pressure \>185/110 mmHg), despite medical therapy, or clinical suspicion of acute systemic inflammation.
• Presence of intracranial haemorrhage on brain MRI/CT.
• Medical history: heart attack within the last 6 weeks, intracerebral bleeding or neurosurgical operation within the last 4 weeks, therapy with anticoagulation, allergic reaction to contrast agent, hemorrhagic diathesis, aneurysms, inflammatory vascular diseases (eg, giant cell arteritis, granulomatosis with polyangitis), endocarditis, or gastric ulcer.
• No willingness and ability of the patient to participate in all follow-up examinations.
• Pregnancy (if suspicion of pregnancy s-hCG or u-hCG must be negative).
• Allergy or intolerance to any ingredients of IMP or placebo or gentamicin.
• Other conditions / circumstances likely to lead to poor treatment adherence (eg, history of poor compliance, alcohol or drug dependency, no fixed abode).
• Significant bleeding disorder either at present or within the past 6 months.
• Effective oral anticoagulant treatment, eg, warfarin sodium (INR \>1.3).
• Effective anticoagulant treatment with heparin or low molecular weight heparin the last 48 hours.
• Any history of central nervous system damage (ie, neoplasm, aneurysm, intracranial or spinal surgery).
• Known hemorrhagic diathesis.
• Major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months (this includes any trauma associated with acute myocardial infarction).

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (18)

University Hospital Antwerp

Antwerp, Belgium

Location

University Hospital Leuven

Leuven, 3000, Belgium

Location

Aarhus University Hospital

Aarhus, Denmark

Location

Bispebjerg University Hospital

Copenhagen, Denmark

Location

Rigshospitalet University Hospital

Copenhagen, Denmark

Location

Helsinki University Hospital

Helsinki, Finland

Location

Turku University Hospital

Turku, Finland

Location

Kauno Klinikos Kaunas

Kaunas, Lithuania

Location

Vilnius University Hospital

Vilnius, Lithuania

Location

Haukeland University Hospital

Bergen, Norway

Location

Vestre Viken Hospital Trust Drammen

Drammen, Norway

Location

Østfold Hospital Trust Kalnes, Dept of Ophthalmology

Grålum, Norway

Location

Helse Nord Trøndelag Trust

Namsos, Norway

Location

Oslo University Hospital

Oslo, 0424, Norway

Location

Telemark Hospital Trust

Skien, Norway

Location

St Olav University Hospital

Trondheim, Norway

Location

Vestfold Hospital Trust

Tønsberg, Norway

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Related Publications (1)

• Ryan SJ, Jorstad OK, Skjelland M, Pesonen M, Simonsen CZ, Bek T, Blauenfeldt RA, Ijas P, Laitinen A, Khanevski A, Krohn J, Rodahl E, Lemmens R, Demeestere J, Cassiman C, Nakstad I, Evensen K, Sandell T, Hamann S, Truelsen TC, Christensen LM, Rosenbaum S, Matijosaitis V, Zemaitiene R, Ellekjaer H, Almaas E, Austeng D, Mazya MV, Traisk F, Ylikotila P, Salmi U, Jenssen KN, Lisether H, Breivik C, Devik K, Honningsvag LE, Valaikiene J, Cimbalas A, Malmberg VN, Anderson E, Roy A, Skattor TH, Kraglund KL, Kefaloykos C, Olsen IC, Vanacker P, Strbian D, Moe MC, Aamodt AH; TenCRAOS Investigators. A Randomized Trial of Tenecteplase in Acute Central Retinal Artery Occlusion. N Engl J Med. 2026 Jan 29;394(5):442-450. doi: 10.1056/NEJMoa2508515.

  PMID: 41604638 DERIVED

MeSH Terms

Conditions

Retinal Artery Occlusion

Interventions

Tenecteplase; Aspirin

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD

Model Details: A prospective, randomized-controlled, double-dummy, double-blind phase 3 multi-centre trial of TNK 0.25 mg/kg + placebo vs. ASA + placebo (2 arms with 1:1 block randomisation). At all participating centers, ophthalmologists are involved in the diagnosis and visual outcome measurements using a standardized protocol. The patients will be promptly examined by the ophthalmologist. As soon as the CRAO is diagnosed by the ophthalmologist, the patients will be managed in the stroke unit during treatment, monitoring, and medical investigations. After treatment in the stroke unit, the patients will be re-examined by an ophthalmologist and a neurologist as an out-patient at (30 ±5) and 90 (±15) days.

Study Record Dates

• First Submitted: August 20, 2020
• First Posted: August 26, 2020
• Study Start: October 30, 2020
• Primary Completion: June 20, 2025
• Study Completion: June 20, 2025
• Last Updated: September 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Protocol is planned to be published in peer-reviewed journal in 2023
• Access Criteria: Protocol is planned to be published in peer-reviewed journal in 2023 and will be available at the journal site

Locations

NO (8); DK (3); FI (2); LI (2); SE (1); BE (2)