TENecteplase in Central Retinal Artery Occlusion Study (TEN-CRAOS): A randomised-controlled, double-dummy, double-blind trial of tenectecteplase vs. ASA for CRAO

TENECTEPLASE IN CENTRAL RETINAL ARTERY OCCLUSION STUDY (TenCRAOS)This Prospective, randomised-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) started 30 October 2020.Today the trial is running in Norway, Finland, Lithuania, Sweden, Denmark and Belgium. By the end of 2023 56 of 78 patients were included.The inclusion is expected to be completed in the first half year of 2024. Centers: Norway: Oslo University Hospital, Haukeland University Hospital, St. Olav Hospital, Stavanger University Hospital, University Hospital of North Norway, Sørlandet Hospital Trust, Vestfold Hospital Trust, Vestre Viken Hospital Trust, Telemark Hospital Trust, Østfold Hospital Trust, Nordmøre and Romsdal Regional Hospital, Innlandet Hospital Trust Lillehammer, Helse Nord Trøndelag Trust. Denmark: Aarhus University Hospital, Copenhagen University Hospital. Sweden: Karolinska University Hospital, Sundvall Finland: Helsinki University Hospital, Turku University Hospital. Belgium: University Hospital Antwerp, Leuven, Brussels and Erasme. Ireland: Mater Misericordiae University Hospital Lithuania: Vilnius University Hospital Santaros klinikos, Republican Vilnius University Hospital, Hospital of Lithuanian University of Health Sciences - Kauno klinikos. The study have been presented at ESOC, EAN, WSC in 2023. Numerous study meetings have been helt.

Tenecteplase in Central Retinal Artery Occlusion (TenCRAOS)This prospective, randomised-controlled, double-dummy, double-blind phase 3 multi-centre international trial of TNK 0.25 mg/kg + placebo vs. ASA + placebo started inclusion in October 2020 in Norway. Today the trial is running in Finland, Lithuania, Sweden, Denmark and Belgium. As of today, 29 of the planned 78 patients have been included. Sponsor Oslo University Hospital. Phase III interventional study. Investigational Medical Product: Tenecteplase (TNK) and NaCl.Centers: Norway: Oslo University Hospital, Haukeland University Hospital, St. Olav Hospital, Stavanger University Hospital, University Hospital of North Norway, Sørlandet Hospital Trust, Vestfold Hospital Trust, Vestre Viken Hospital Trust, Telemark Hospital Trust, Østfold Hospital Trust, Nordmøre and Romsdal Regional Hospital, Innlandet Hospital Trust Lillehammer, Helse Nord Trøndelag Trust. Denmark: Aarhus University Hospital, Copenhagen University Hospital. Sweden: Karolinska University Hospital, Sundvall Finland: Helsinki University Hospital, Turku University Hospital. Belgium: University Hospital Antwerp, Leuven, Brussels and Erasme - all are activated. Ireland: Mater Misericordiae University Hospital, University Hospital Waterford, University Hospital Limerick. Lithuania: Vilnius University Hospital Santaros klinikos, Republican Vilnius University Hospital, Hospital of Lithuanian University of Health Sciences - Kauno klinikos. Austria: Salzburg University Hospital, more Austrian centers are being recruited. Melbourne Lithuania, Finland, Sweden, Denmark and Norway have included patients whereas all the Belgian centers are activated. Both the Austrian and Australian centers are preparing for start-up. The study have been presented at ESOC, EAN, WSC in 2022. Numerous study meetings have been helt.

Tenecteplase in Central Retinal Artery Occlusion (TenCRAOS)This prospective, randomised-controlled, double-dummy, double-blind phase 3 multi-centre international trial of TNK 0.25 mg/kg + placebo vs. ASA + placebo started inclusion in October 2020 in Norway. Today the trial is running in Finland, Lithuania, Sweden, Denmark and Belgium. As of today, 8 of the planned 78 patients have been included.Sponsor Oslo University Hospital. Phase III interventional study. Investigational Medical Product: Tenecteplase (TNK) and NaCl. Centers: Norway: Oslo University Hospital, Haukeland University Hospital, St. Olav Hospital, Stavanger University Hospital, University Hospital of North Norway, Sørlandet Hospital Trust, Vestfold Hospital Trust, Vestre Viken Hospital Trust, Telemark Hospital Trust, Østfold Hospital Trust, Nordland Hospital Trust, Nordmøre and Romsdal Regional Hospital, Innlandet Hospital Trust Lillehammer, Helse Nord Trøndelag Trust. Denmark: Aarhus University Hospital, Copenhagen University Hospital. Sweden: Karolinska University Hospital, Sundvall Finland: Helsinki University Hospital, Turku University Hospital. Belgium: University Hospital Antwerp. More Belgian centers are being activated. Ireland: Mater Misericordiae University Hospital, University Hospital Waterford, University Hospital Limerick. Lithuania: Vilnius University Hospital Santaros klinikos, Republican Vilnius University Hospital, Hospital of Lithuanian University of Health Sciences - Kauno klinikos. Portugal: Centro Hospitalar Universitário de São João, more Portuguese centres are being recruited. Austria: Salzburg University Hospital. Study Period: Estimated date of first patient enrolled: October 2020. Anticipated recruitment period: October 2020 to September 2023 Estimated date of last patient completed: January 2024. End of study defined as last patient visit. Treatment Duration: Expected treatment duration pr. patient: 1 day. Follow-up: Expected follow-up period pr. patient 90 (±15) days. Objectives To assess the effect of systemic tenecteplase within 4.5 hours of onset of CRAO. Endpoints: Primary endpoint: Proportion of patients with ≤ 0.7 logMAR best-corrected visual acuity in the affected eye at 30 (±5) days after treatment, representing an improvement in best-corrected visual acuity of at least 0.3 logMAR (intention-to-treat (ITT) analysis). Secondary endpoints: 1. Proportion of patients with ≤ 0.5 logMAR best-corrected visual acuity in the affected eye at 30 (±5) and 90 (±15) days. 2. Mean improvement in logMAR best-corrected visual acuity in the affected eye from baseline to 30 (±5) and 90 (±15) days. 3. 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. 4. Number of test points seen (of 100) on monocular Esterman perimetry at 30 (±5) and 90 (±15) days. 5. Acute ischemic lesions on follow-up on diffusion-weighted (DWI) MRI or on brain CT at baseline and 24hrs. 6. National Institutes of Health Stroke Scale score (NIHSS) at 24hrs and discharge. 7. Modified Rankin Scale score (mRS) at discharge, 30 (±5) and 90 days (±15) days. 8. Mean score on National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) at 30 (±5) and 90 (±15) days (1). 9. Mean score on EQ-5D at 30 (±5) and 90 (±15) days. 10. Presence of ocular neovascularisation at 30 (±5) and 90 (±15) days. Safety endpoints: 11. All-cause and stroke-related death at discharge, 30 (±5) and 90 (±15) days. 12. Proportion of patients with any intracranial haemorrhage at 24 hrs. 13. Proportion of patients with symptomatic intracranial haemorrhage until discharge. 14. Proportion of patients with complications such as systemic bleeding at 24 hrs, discharge and 30 (±5) days. 15. Other serious adverse events. 16. Occurrence of adverse events.

BLODPROPPLØSENDE MEDISIN VED BLODPROPP I ØYETVed blodpropp i øyet – såkalt sentralarterieokklusjon i netthinnen i øyet - er det stor risiko for permanent blindhet. Per i dag finnes ingen dokumentert effektiv behandling for å fjerne blodproppen. I denne internasjonale studien tester vi effekten av blodproppløsende medisin hos personer med blodpropp i øyetPasienten undersøkes raskt hos øyelege som diagnostiserer tilstanden, og overflyttes deretter til akuttbehandling ved nærmeste slagenhet for behandling og utredning innen 4,5 timer etter symptomdebut. Oppfølging er etter 30 og 90 dager hos øyelege og nevrolog. Studien ledes fra Oslo universitetssykehus og foregår i alle helseregioner i Norge og i 7 andre land. I denne studien skal effekten av en ny blodproppløsende medisin sammenlignes med dagens behandling. Per i dag er det ikke dokumentert noen effektiv blodproppløsende behandling ved blodpropp i øyet. Det gis derfor ingen spesiell medisin, men vi gjør undersøkelser for å kartlegge hvor blodproppen kommer fra, årsaken til blodproppen, samt at vi følger opp tilstanden i øyet med undersøkelser hos øyelege. Ved blodpropp i hjernen, altså hjerneslag, er det godt dokumentert at blodproppløsende medisin virker. Blodpropp i øyet har en del likheter med blodpropp i hjernen og vi vil derfor teste ut effekten av samme type medisin. For å gjøre utprøvingen systematisk, er studiemedisin slik at halvparten av dosene som brukes inneholder blodproppløsende medisin og den andre inneholder saltvann, såkalt placebo. Verken pasient eller behandler vil derfor ikke vite om studiemedisinen inneholder blodproppløsende medisin eller saltvann mens studien pågår. Når studiemedisin gis, gjøres monitorering og observasjoner etter rutine ved denne typen behandling med hyppige målinger av blodtrykk, puls og nevrologisk funksjon det første døgnet. Vi gjør også en radiologisk bildeundersøkelse av hjernen (CT eller MR). Det første døgnet er det derfor ekstra undersøkelser. Utover dette er det ingen ekstra undersøkelser utover rutineundersøkelsen etter 1 og 3 måneder blir stilt noen spørsmål. Det er per i dag standard behandling å starte med tablett med blodfortynnende medisin som også gis i regi av studien. Datainnsamling er planlagt i 3 år eller til minst 78 pasienter er inkludert.