Sven Poli, Carsten Grohmann, Daniel A. Wenzel, Khouloud Poli, Johannes Tuennerhoff, Max Nedelmann, Jens Fiehler, Hansjürgen Agostini, Bruce Campbell, Dominik M. Fischer, Marek Sykora, Brian Mac Grory, Nicolas Feltgen, David J Seiffge, Daniel Strbian, Maximilian Schultheiß, Martin S. Spitzer
{"title":"用静脉注射阿替普酶进行早期再灌注治疗以恢复急性视网膜中央动脉闭塞患者的视力(REVISION):III 期试验研究方案","authors":"Sven Poli, Carsten Grohmann, Daniel A. Wenzel, Khouloud Poli, Johannes Tuennerhoff, Max Nedelmann, Jens Fiehler, Hansjürgen Agostini, Bruce Campbell, Dominik M. Fischer, Marek Sykora, Brian Mac Grory, Nicolas Feltgen, David J Seiffge, Daniel Strbian, Maximilian Schultheiß, Martin S. Spitzer","doi":"10.1177/17474930241248516","DOIUrl":null,"url":null,"abstract":"Rationale:Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data is lacking to address this question.Aims:REVISION investigates intravenous alteplase within 4.5 hours of monocular vision loss due to acute CRAO.Methods:Randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial.Study outcomes:Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best corrected visual acuity of the Logarithm of the Minimum An-gle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy out-comes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomogra-phy/angiography, ultrasound and MRI biomarkers will be conducted.Sample size:Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm.Discussion:By enrolling patients within 4.5 hours of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may trans-late to CRAO with its similar pathophysiology.Trial registration:ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.","PeriodicalId":14442,"journal":{"name":"International Journal of Stroke","volume":null,"pages":null},"PeriodicalIF":6.3000,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Early REperfusion Therapy with Intravenous Alteplase for Recovery of VISION in Acute Central Retinal Artery Occlusion (REVISION): Study Protocol of a Phase III Trial\",\"authors\":\"Sven Poli, Carsten Grohmann, Daniel A. Wenzel, Khouloud Poli, Johannes Tuennerhoff, Max Nedelmann, Jens Fiehler, Hansjürgen Agostini, Bruce Campbell, Dominik M. Fischer, Marek Sykora, Brian Mac Grory, Nicolas Feltgen, David J Seiffge, Daniel Strbian, Maximilian Schultheiß, Martin S. Spitzer\",\"doi\":\"10.1177/17474930241248516\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Rationale:Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data is lacking to address this question.Aims:REVISION investigates intravenous alteplase within 4.5 hours of monocular vision loss due to acute CRAO.Methods:Randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial.Study outcomes:Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best corrected visual acuity of the Logarithm of the Minimum An-gle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy out-comes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomogra-phy/angiography, ultrasound and MRI biomarkers will be conducted.Sample size:Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm.Discussion:By enrolling patients within 4.5 hours of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may trans-late to CRAO with its similar pathophysiology.Trial registration:ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.\",\"PeriodicalId\":14442,\"journal\":{\"name\":\"International Journal of Stroke\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.3000,\"publicationDate\":\"2024-04-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Stroke\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17474930241248516\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Stroke","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17474930241248516","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Early REperfusion Therapy with Intravenous Alteplase for Recovery of VISION in Acute Central Retinal Artery Occlusion (REVISION): Study Protocol of a Phase III Trial
Rationale:Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data is lacking to address this question.Aims:REVISION investigates intravenous alteplase within 4.5 hours of monocular vision loss due to acute CRAO.Methods:Randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial.Study outcomes:Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best corrected visual acuity of the Logarithm of the Minimum An-gle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy out-comes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomogra-phy/angiography, ultrasound and MRI biomarkers will be conducted.Sample size:Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm.Discussion:By enrolling patients within 4.5 hours of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may trans-late to CRAO with its similar pathophysiology.Trial registration:ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.
期刊介绍:
The International Journal of Stroke is a welcome addition to the international stroke journal landscape in that it concentrates on the clinical aspects of stroke with basic science contributions in areas of clinical interest. Reviews of current topics are broadly based to encompass not only recent advances of global interest but also those which may be more important in certain regions and the journal regularly features items of news interest from all parts of the world. To facilitate the international nature of the journal, our Associate Editors from Europe, Asia, North America and South America coordinate segments of the journal.