Early Reperfusion Therapy for Recovery of Vision in Acute Central Retinal Artery Occlusion

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Tuebingen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

8 Sep 2022 → 29 Apr 2026

Decision date (initial)

2023-10-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BMBF

External identifiers

EU CT number

2023-507388-21-00

EudraCT number

2021-000183-29

ClinicalTrials.gov

NCT04965038

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

Functional recovery to best corrected visual acuity (BCVA) of Logarithm
of the Minimum Angle of Resolution (LogMAR) ≤ 0.5 (normal to mild
vision impairment according to WHO ICD-11 (WHO, 2019)) in the
affected eye at Visit (V) 3 (30 ± 5 days), dichotomized ITT analysis
(functional recovery to LogMAR ≤ 0.5 vs. no functional recovery, i.e.,
LogMAR > 0.5)

Secondary objectives 1

1. To investigate efficacy of IVT using alternative endpoints as well as to investigate safety of IVT in non-arteritic CRAO.

Conditions and MedDRA coding

Acute non-arteritic central retinal artery occlusion (CRAO)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥ 18 years
2. 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)
3. BCVA of LogMAR ≥ 1.3 in the affected eye (functional blindness according to WHO ICD-11)
4. Reading must have been possible with the affected eye before CRAO (LogMAR ≤ 0.5)
5. Neurological examination performed by an experienced stroke neurologist
6. Brain imaging as per local standard for acute retinal ischemia/stroke assessment, either cranial computed tomography (CT) or cranial magnetic resonance imaging (MRI)

Exclusion criteria 6

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary efficacy endpoint of the interventional study: Functional recovery to best corrected visual acuity (BCVA) of Logarithm of the Minimum Angle of Resolution (LogMAR) ≤ 0.5 (normal to mild vision impairment according to WHO ICD-11) in the affected eye at Visit (V) 3 (30 ± 5 days), intention-to-treat (ITT) analysis

Secondary endpoints 12

1. Functional recovery to LogMAR ≤ 0.5 at V3 (30 ± 5 days) (dichotomized) in the per protocol population
2. Functional recovery to LogMAR ≤ 0.5 at V2 (18 – 72 hours), and V4 (90 ± 10 days) (dichotomized)
3. Shift in visual outcome categories (according to WHO ICD-11 (WHO, 2019): normal vision (LogMAR ≤ 0), mild visual impairment (LogMAR > 0 and ≤ 0.5), moderate visual impairment (LogMAR > 0.5 and ≤ 1.0), severe visual impairment (LogMAR > 1.0 and ≤ 1.3), counting fingers (LogMAR > 1.3 and ≤ counting fingers), hand motion or light perception, and no light perception) at V2, V3, and V4
4. Dichotomized analysis of visual outcome: ‘normal vision to moderate visual impairment’ vs. ‘severe visual impairment or functional blindness’ and ‘normal vision to severe visual impairment’ vs. ‘functional blindness’ at V2, V3, and V4
5. Kinetic visual field using III4e mark at V3 and V4 (as a continuous variable)
6. Central retinal artery recanalization assessed using OCTA of the optic nerve head and the macula at V2, V3, and V4 (continuous)
7. Retinal arterial perfusion assessed using fluorescein angiography at V3 and V4 (continuous)
8. NEI-VFQ-25 at V3 and V4 (continuous)
9. NIHSS at V2 (continuous)
10. mRS at V3, and V4 (dichotomized into categories 0 – 1 (excellent outcome) vs. 2 – 6, 0 – 2 (functional independence) vs. 3 – 6, and shift analysis)
11. Fraction of patients with, number, and volume of acute ischemic lesions on follow-up diffusionweighted (DWI) cranial magnetic resonance imaging (MRI) at V2 (dichotomous and continuous, respectively)
12. Any bleeding until V2 by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 classification of adverse events (AE), i.e., mild, moderate, severe, life-threatening, leading to death.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Tuebingen AöR

Sponsor organisation

Universitaetsklinikum Tuebingen AöR

Address

Geissweg 3, Innenstadt Innenstadt

City

Tübingen

Postcode

72076

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Dept. of Neurology and Stroke

Public contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Dept. of Neurology and Stroke

Third parties 4

Locations

1 EU/EEA country · 39 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications