TENecteplase in Central Retinal Artery Occlusion Stuy (TenCRAOS)

Central Retinal Artery Occlusion Clinical Trial

— TenCRAOS  

Official title:

TENecteplase in Central Retinal Artery Occlusion Study (TenCRAOS): A Randomized Placebo-controlled Trial of Early Systemic Tenecteplase Treatment in Patients With Central Retinal Artery Occlusion.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04526951
• Other study ID #: Oslo UH
• Secondary ID: 2018-002546-3620
• Status: Recruiting
• Phase: Phase 3
• Start date: October 30, 2020
• Est. completion date: May 31, 2024

Study information

• Verified date: January 2023
• Source: Oslo University Hospital
• Contact: Anne Hege Aamodt
• Phone: +47 23074976
• Email: a.h.aamodt[@]medisin.uio.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

Central retinal artery occlusion (CRAO) is an ophthalmologic emergency that, without prompt revascularization, bears high risk of permanent blindness. The condition is typically the result of an artery-to-artery embolism from a carotid plaque or cardio embolism. A recent meta-analysis of observational data indicates that prompt revascularization with systemic thrombolysis might improve outcome. A randomized controlled trial of early systemic thrombolysis for CRAO is therefore warranted. The aim of this project is to assess the effect of systemic tissue plasminogen activator tenecteplase versus placebo administered within 4.5 hours of CRAO onset in patients admitted to the participating hospitals in Europe. The main endpoint is the proportion of patients with ≤ 0.7 logMAR visual acuity 30 (±5) days after treatment, representing an improvement in visual acuity of at least 0.3 logMAR, equal to at least 15 letters/three lines on a visual acuity chart. In addition, we will access differences in visual field parameters and patient reported outcome measures between the groups. This study is based on a broad collaboration and interaction between leading ophthalmologists and neurologists in European centres.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: May 31, 2024
• Est. primary completion date: February 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Non-arteritic central retinal artery occlusion with = 1.0 logMAR visual acuitiy and symptoms lasting less than 4.5 hours.

2. Ability to administer the Investigator Medicinal Product (IMP) within 4.5 hours of symptom onset.

3. Age =18 years.

4. Informed written consent of the patient.

5. 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.

Exclusion Criteria:

1. No other active intervention targeting CRAO.

2. 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).

3. Systemic diseases; severe general diseases, systemic arterial hypertension (blood pressure >185/110 mmHg), despite medical therapy, or clinical suspicion of acute systemic inflammation.

4. Presence of intracranial haemorrhage on brain MRI/CT.

5. 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.

6. No willingness and ability of the patient to participate in all follow-up examinations.

7. Pregnancy (if suspicion of pregnancy s-hCG or u-hCG must be negative).

8. Allergy or intolerance to any ingredients of IMP or placebo or gentamicin.

9. Other conditions / circumstances likely to lead to poor treatment adherence (eg, history of poor compliance, alcohol or drug dependency, no fixed abode).

10. Significant bleeding disorder either at present or within the past 6 months.

11. Effective oral anticoagulant treatment, eg, warfarin sodium (INR >1.3).

12. Effective anticoagulant treatment with heparin or low molecular weight heparin the last 48 hours.

13. Any history of central nervous system damage (ie, neoplasm, aneurysm, intracranial or spinal surgery).

14. Known hemorrhagic diathesis.

15. Major surgery, biopsy of a parenchymal organ, or significant trauma within the past 2 months (this includes any trauma associated with acute myocardial infarction).

16. Recent non-compressible vessel puncture within 2 weeks.

17. Recent trauma to the head or cranium.

18. Prolonged cardiopulmonary resuscitation (>2 minutes) within the past 2 weeks.

19. Acute pericarditis and/or subacute bacterial endocarditis.

20. Acute pancreatitis.

21. Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal varices) and active hepatitis.

22. Active peptic ulceration.

23. Arterial aneurysm and known arterial/venous malformation.

24. Neoplasm with increased bleeding risk.

25. Any known history of hemorrhagic stroke or stroke of unknown origin.

26. Known history of ischemic stroke or transient ischemic attack in the preceding 3 months.

27. Dementia.

Related Conditions & MeSH terms

• Arterial Occlusive Diseases
• Central Retinal Artery Occlusion
• Retinal Artery Occlusion

Intervention

Drug:
• Intravenous injection of Tenecteplase and one dose of placebo tablet
Drug: Tenecteplase Tenecteplase administered as an intravenous injection (0.25 mg/kg body weigh; maximum 25 mg)
• One tablet of Acetylsalicylic Acid and one dose of IV placebo
300 mg Acetylsalisylic acid

Locations

Country	Name	City	State
Australia	St Vincent's Hospital Melbourne	Melbourne
Austria	Universitätsklinik für Neurologie Christian-Doppler-Klinik Salzburg	Salzburg
Belgium	ULB-Hôpital Erasme	Anderlecht
Belgium	University Hospital Antwerp	Antwerp
Belgium	UZ Brussel	Brussel
Belgium	University Hospital Leuven	Leuven
Denmark	Aarhus University Hospital	Aarhus
Denmark	Rigshospitalet University Hospital	Copenhagen
Finland	Helsinki University Hospital	Helsinki
Finland	Turku University Hospital	Turku
Ireland	Mater Misericordiae University Hospital	Dublin
Ireland	University Hospital Galway	Galway
Ireland	University Hospital Limerick	Limerick
Ireland	University Hospital Waterford	Waterford
Lithuania	Kauno Klinikos Kaunas	Kaunas
Lithuania	Respublican Vilnius University Hospital	Vilnius
Lithuania	Vilnius University Hospital	Vilnius
Norway	Sørlandet Hospital Trust	Arendal
Norway	Haukeland University Hospital	Bergen
Norway	Vestre Viken Hospital Trust Drammen	Drammen
Norway	Østfold Hospital Trust Kalnes, Dept of Ophthalmology	Grålum
Norway	Innlandet Hospital Trust	Lillehammer
Norway	Nordmøre and Romsdal Regional Hospital	Molde
Norway	Helse Nord Trøndelag Trust	Namsos
Norway	Oslo University Hospital	Oslo
Norway	Telemark Hospital Trust	Skien
Norway	Stavanger University Hospital	Stavanger
Norway	Vestfold Hospital Trust	Tønsberg
Norway	University Hospital of North Norway, Tromsø	Tromsø
Norway	St Olav University Hospital	Trondheim
Sweden	Karolinska University Hospital	Stockholm
Sweden	Sundsvall Hospital	Sundsvall

Sponsors (1)

Lead Sponsor	Collaborator
Oslo University Hospital

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Denmark,  Finland,  Ireland,  Lithuania,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	All-cause and stroke-related death at discharge, 30 (±5) and 90 (±15) days.	Mortality	Discharge assessed up to 7 days , 30 (±5) and 90 (±15) days
Other	Proportion of patients with any intracranial haemorrhage at 24 hrs	Intracranial haemorrhage	24 hours
Other	Proportion of patients with symptomatic intracranial haemorrhage until discharge.	Symptomatic intracranial haemorrhage	at discharge, assessed up to 7 days
Other	Proportion of patients with complications such as systemic bleeding at 24 hrs, discharge and 30 (±5) days	Systemic bleeding	24 hours, at discharge assessed up to 7 days and 30 (±5) days
Other	Other serious adverse events	Frequency of serious adverse events	24 hours, at discharge, 30 (±5) days and 90 days (±15) days.
Other	Occurrence of adverse events	Frequency of adverse events	24 hours, at discharge assessed up to 7 days, 30 (±5) days and 90 days (±15) days.
Other	Retrobulbar spot sign detection using Duplex/Doppler ultrasound at baseline, point-of-care ultrasound (POCUS)	Frequency of retrobulbar spot sign	30 (±5) and 90 (±15) days
Other	Retrobulbar spot sign and central retinal artery recanalisation using Duplex/Doppler ultrasound at 24h and discharge	Frequency of retrobulbar spot sign	24 hours and at discharge assessed up to 7 days
Other	Macular optical coherence tomography (OCT) volume scans and macular OCT angiography (OCT-A) at 30 and 90 days	OCT measures	30 (±5) and 90 (±15) days
Primary	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	Proportion of patients with = 0.5 logMAR visual acuity in the affected eye at 30 (±5) and 90 (±15) days.	logMAR	30 (±5) and 90 (±15) days
Secondary	Mean improvement in logMAR visual acuity in the affected eye from baseline to 30 (±5) and 90 (±15) days.	logMAR	30 (±5) and 90 (±15) days
Secondary	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	logMAR	30 (±5) and 90 (±15) days
Secondary	Number of test points seen (of 100) on monocular Esterman perimetry at 30 (±5) and 90 (±15) days	Number of test points	30 (±5) and 90 (±15) days
Secondary	Acute ischemic lesions on follow-up on diffusion-weighted (DWI) MRI or on brain CT at baseline and 24hrs.	DWI lesions	24 hours
Secondary	National Institutes of Health Stroke Scale score (NIHSS) at 24hrs and discharge.	NIHSS score	24 hours
Secondary	Modified Rankin Scale score (mRS) at discharge, 30 (±5) and 90 days (±15) days.	mRS score	Discharge, 30 (±5) and 90 days (±15) days.
Secondary	Mean score on National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) at 30 (±5) and 90 (±15) days	Visual function related quality of life at 30 and 90 days. Measures the dimensions of self-reported vision-targeted health status that are most important for persons who have chronic eye diseases. 100 = best possible, 0 = worst possible	30 (±5) and 90 (±15) days
Secondary	Mean score on EQ-5D at 30 (±5) and 90 (±15) days	Quality of life reported at 30 and 90 days. Health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.	30 (±5) and 90 (±15) days
Secondary	Presence of ocular neovascularisation at 30 (±5) and 90 (±15) days	presence	30 (±5) and 90 (±15) days