Early Reperfusion Therapy With Intravenous Thrombolysis for Recovery of VISION in Acute Central Retinal Artery Occlusion

NCT04965038 | Recruiting Phase 3 DMC

• 1 other identifier: 2021-000183-29
• Study Type: interventional
• Target: 422
• Locations: 1 country
• Sites: 1

Brief Summary

Non-arteritic, thromboembolic central retinal artery occlusion (CRAO) is an acute neurovascular-ophthalmological emergency which leads to severe and permanent vision loss; no evidence-based therapy does exist. Two recent meta-analyses indicate early intravenous thrombolysis to be beneficial in CRAO. Therefore, the REVISION randomized placebo-controlled interventional trial will investigate intravenous alteplase in CRAO as it is practiced in acute ischemic stroke, i.e. within 4.5 hours after symptom onset. The REVISION observational study will evaluate retinal changes on optical coherence tomography (OCT) in patients within 12 hours of CRAO onset, and the REVISION substudy, which will be conducted adjunct to either the interventional or the observational study, will evaluate the value of the retrobulbar spot sign for prediction of outcome and treatment response.

Conditions

Central Retinal Artery Occlusion

Keywords

Central Retinal Artery Occlusion; Thrombolysis; Alteplase

Outcome Measures

Primary Outcomes (1)

• Functional recovery at visit 3

  Functional recovery to best corrected visual acuity of logarithm of the minimum angle of resolution ≤ 0.5 in the affected eye, which corresponds to normal to mild vision impairment (intention-to-treat analysis).

  30 days

Secondary Outcomes (17)

• best corrected visual acuity (BCVA) at visits 2, 3, and 4

  90 days

• Shift in visual outcome categories at visits 2, 3, and 4

  90 days

• Dichotomized analysis of visual outcome at visits 2, 3, and 4

  90 days

• Visual field at visits 3 and 4

  90 days

• Central retinal artery recanalization at visits 2, 3, and 4

  90 days

Other Outcomes (3)

• Exploratory Outcomes of the REVISION Interventional Study

  90 days

• Exploratory Outcomes of the REVISION Observational Study

  1 day

• Exploratory Outcomes of the Retrobulbar Spot Sign Substudy

  30 days

Study Arms (3)

Thrombolysis (interventional study)

ACTIVE COMPARATOR

Tenecteplase (0.25 mg per kg body weight as bolus; until trial protocol V04: Alteplase \[0.9 mg per kg body weight; 10% as bolus; remaining over one hour\] will be administered intravenously within 4.5 hours of symptom onset

Drug: Tenecteplase (until trial protocol V04: Alteplase)

Placebo (interventional study)

PLACEBO COMPARATOR

Placebo (0.25 mg per kg body weight as bolus; until trial protocol V04: 0.9 mg per kg body weight; 10% as bolus; remaining over one hour) will be administered intravenously within 4.5 hours of symptom onset

Drug: Tenecteplase (until trial protocol V04: Alteplase)

Observational study

NO INTERVENTION

The prospective REVISION observational study will enroll patients within 12 hours of symptom onset

Interventions

Tenecteplase (until trial protocol V04: Alteplase) DRUG

Intravenous thrombolysis within 4.5 hours of symptom onset

Placebo (interventional study); Thrombolysis (interventional study)

Eligibility Criteria

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

You may qualify if:

• Acute non-arteritic CRAO (i.e. sudden, painless monocular vision loss) ≤ 12 hours after symptom onset confirmed by an experienced ophthalmologist through assessment of: BCVA, intraocular pressure, swinging flash light test (relative afferent pupil defect), slit-lamp biomicroscopy, fundoscopy, and OCT of the macula of both eyes\* (\*within the 4.5-hour time window: to be skipped if not feasible ≤ 10 minutes; beyond the 4.5-hour time window: mandatory)
• BCVA of LogMAR ≥ 1.3 in the affected eye (functional blindness according to WHO ICD-11)
• Reading must have been possible with the affected eye before CRAO (LogMAR ≤ 0.5)
• Neurological examination performed by an experienced stroke neurologist
• Brain imaging as per local standard for acute retinal ischemia/stroke assessment, either cranial computed tomography (CT) or cranial magnetic resonance imaging (MRI)

You may not qualify if:

• Suspected giant cell arteritis
• Other-than-CRAO cause of acute visual loss (e.g., retinal detachment, vitreous hemorrhage, acute glaucoma, acute optic neuritis)
• BCVA of LogMAR \< 1.3 or rapidly improving vision in the affected eye
• Acute ischemic stroke with indication for on-label intravenous thrombolysis (IVT)
• Any co-existing or terminal disease with anticipated life expectancy of \< 3 months
• Prior participation in the REVISION trial

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Hospital Tuebingen

Tübingen, 72076, Germany

RECRUITING

Related Publications (1)

• Poli S, Grohmann C, Wenzel DA, Poli K, Tunnerhoff J, Nedelmann M, Fiehler J, Burghaus I, Lehmann M, Glauch M, Schadwinkel HM, Kalmbach P, Zeller J, Peters T, Eschenfelder C, Agostini H, Campbell BC, Fischer MD, Sykora M, Mac Grory B, Feltgen N, Kowarik M, Seiffge D, Strbian D, Albrecht M, Alzureiqi MS, Auffarth G, Bazner H, Behnke S, Berberich A, Bode F, Bohmann FO, Cheng B, Czihal M, Danyel LA, Dimopoulos S, Pinhal Ferreira de Pinho JD, Fries FN, Gamulescu MA, Gekeler F, Gomez-Exposito A, Gumbinger C, Guthoff R, Hattenbach LO, Kellert L, Khoramnia R, Kohnen T, Kurten D, Lackner B, Laible M, Lee JI, Leithner C, Liegl R, Lochner P, Mackert M, Mbroh J, Muller S, Nagel S, Prasuhn M, Purrucker J, Reich A, Mundiyanapurath S, Royl G, Salchow DJ, Schafer JH, Schlachetzki F, Schmack I, Thomalla G, Tieck Fernandez MP, Wakili P, Walter P, Wolf A, Wolf M, Bartz-Schmidt KU, Schultheiss M, Spitzer MS. Early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial. Int J Stroke. 2024 Aug;19(7):823-829. doi: 10.1177/17474930241248516. Epub 2024 Jun 25.

  PMID: 38591748 DERIVED

MeSH Terms

Conditions

Retinal Artery Occlusion

Interventions

Tenecteplase

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

Central Study Contacts

Sven Poli

CONTACT

+49-7071-29-0; sven.poli@uni-tuebingen.de

Julia Zeller

CONTACT

+49-7071-29-0; julia.zeller@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2021
• First Posted: July 16, 2021
• Study Start: October 10, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 27, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)