drugset / Trial / NCT05836766
Cilostazol Dexborneol Versus Placebo for Microcirculation Dysfunction After Reperfusion Therapy in Patients With Acute Ischemic Stroke With Large Vessel Occlusion
RandomizedParallel-groupQuadruple-blindTreatment
Summary
This study aims to evaluate the efficacy of Y-6 sublingual tablets in improving microcirculation dysfunction and reducing thrombo-inflammation in patients who had AIS caused by LVO and received reperfusion therapy. Moreover, we expect to evaluate the safety of using Y-6 sublingual tablet in such study population.
Timeline
- Start
- 2023-06-05
- Primary completion
- 2024-07
- Completion
- 2024-08
Publications
- Background Smith WS, Lev MH, English JD, Camargo EC, Chou M, Johnston SC, Gonzalez G, Schaefer PW, Dillon WP, Koroshetz WJ, Furie KL. Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA. Stroke. 2009 Dec;40(12):3834-40. doi: 10.1161/STROKEAHA.109.561787. Epub 2009 Oct 15.
- Background Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016 Apr 23;387(10029):1723-31. doi: 10.1016/S0140-6736(16)00163-X. Epub 2016 Feb 18.
- Background van Horn N, Kniep H, Leischner H, McDonough R, Deb-Chatterji M, Broocks G, Thomalla G, Brekenfeld C, Fiehler J, Hanning U, Flottmann F. Predictors of poor clinical outcome despite complete reperfusion in acute ischemic stroke patients. J Neurointerv Surg. 2021 Jan;13(1):14-18. doi: 10.1136/neurintsurg-2020-015889. Epub 2020 May 15.
- Background Ng FC, Coulton B, Chambers B, Thijs V. Persistently Elevated Microvascular Resistance Postrecanalization. Stroke. 2018 Oct;49(10):2512-2515. doi: 10.1161/STROKEAHA.118.021631.
- Background Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G, Grotta J, Howard G, Kaste M, Koga M, von Kummer R, Lansberg M, Lindley RI, Murray G, Olivot JM, Parsons M, Tilley B, Toni D, Toyoda K, Wahlgren N, Wardlaw J, Whiteley W, del Zoppo GJ, Baigent C, Sandercock P, Hacke W; Stroke Thrombolysis Trialists' Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014 Nov 29;384(9958):1929-35. doi: 10.1016/S0140-6736(14)60584-5. Epub 2014 Aug 5.
- Background Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-e418. doi: 10.1161/STR.0000000000000211. Epub 2019 Oct 30.
- Background Hussein HM, Georgiadis AL, Vazquez G, Miley JT, Memon MZ, Mohammad YM, Christoforidis GA, Tariq N, Qureshi AI. Occurrence and predictors of futile recanalization following endovascular treatment among patients with acute ischemic stroke: a multicenter study. AJNR Am J Neuroradiol. 2010 Mar;31(3):454-8. doi: 10.3174/ajnr.A2006. Epub 2010 Jan 14.
- Background Casetta I, Fainardi E, Saia V, Pracucci G, Padroni M, Renieri L, Nencini P, Inzitari D, Morosetti D, Sallustio F, Vallone S, Bigliardi G, Zini A, Longo M, Francalanza I, Bracco S, Vallone IM, Tassi R, Bergui M, Naldi A, Saletti A, De Vito A, Gasparotti R, Magoni M, Castellan L, Serrati C, Menozzi R, Scoditti U, Causin F, Pieroni A, Puglielli E, Casalena A, Sanna A, Ruggiero M, Cordici F, Di Maggio L, Duc E, Cosottini M, Giannini N, Sanfilippo G, Zappoli F, Cavallini A, Cavasin N, Critelli A, Ciceri E, Plebani M, Cappellari M, Chiumarulo L, Petruzzellis M, Terrana A, Cariddi LP, Burdi N, Tinelli A, Auteri W, Silvagni U, Biraschi F, Nicolini E, Padolecchia R, Tassinari T, Filauri P, Sacco S, Pavia M, Invernizzi P, Nuzzi NP, Marcheselli S, Amista P, Russo M, Gallesio I, Craparo G, Mannino M, Mangiafico S, Toni D; Italian Registry of Endovascular Treatment in Acute Stroke. Endovascular Thrombectomy for Acute Ischemic Stroke Beyond 6 Hours From Onset: A Real-World Experience. Stroke. 2020 Jul;51(7):2051-2057. doi: 10.1161/STROKEAHA.119.027974. Epub 2020 Jun 17.
- Background Berkhemer OA, Jansen IG, Beumer D, Fransen PS, van den Berg LA, Yoo AJ, Lingsma HF, Sprengers ME, Jenniskens SF, Lycklama A Nijeholt GJ, van Walderveen MA, van den Berg R, Bot JC, Beenen LF, Boers AM, Slump CH, Roos YB, van Oostenbrugge RJ, Dippel DW, van der Lugt A, van Zwam WH, Marquering HA, Majoie CB; MR CLEAN Investigators. Collateral Status on Baseline Computed Tomographic Angiography and Intra-Arterial Treatment Effect in Patients With Proximal Anterior Circulation Stroke. Stroke. 2016 Mar;47(3):768-76. doi: 10.1161/STROKEAHA.115.011788. Epub 2016 Jan 28.
- Background Groot AE, Treurniet KM, Jansen IGH, Lingsma HF, Hinsenveld W, van de Graaf RA, Roozenbeek B, Willems HC, Schonewille WJ, Marquering HA, van den Berg R, Dippel DWJ, Majoie CBLM, Roos YBWEM, Coutinho JM; MR CLEAN Registry Investigators. Endovascular treatment in older adults with acute ischemic stroke in the MR CLEAN Registry. Neurology. 2020 Jul 14;95(2):e131-e139. doi: 10.1212/WNL.0000000000009764. Epub 2020 Jun 11.
- Background Hussein HM, Saleem MA, Qureshi AI. Rates and predictors of futile recanalization in patients undergoing endovascular treatment in a multicenter clinical trial. Neuroradiology. 2018 May;60(5):557-563. doi: 10.1007/s00234-018-2016-2. Epub 2018 Mar 25.
- Background Rubiera M, Garcia-Tornel A, Olive-Gadea M, Campos D, Requena M, Vert C, Pagola J, Rodriguez-Luna D, Muchada M, Boned S, Rodriguez-Villatoro N, Juega J, Deck M, Sanjuan E, Hernandez D, Pinana C, Tomasello A, Molina CA, Ribo M. Computed Tomography Perfusion After Thrombectomy: An Immediate Surrogate Marker of Outcome After Recanalization in Acute Stroke. Stroke. 2020 Jun;51(6):1736-1742. doi: 10.1161/STROKEAHA.120.029212. Epub 2020 May 14.
- Background Raja R, Rosenberg GA, Caprihan A. MRI measurements of Blood-Brain Barrier function in dementia: A review of recent studies. Neuropharmacology. 2018 May 15;134(Pt B):259-271. doi: 10.1016/j.neuropharm.2017.10.034. Epub 2017 Oct 28.
- Background Bai R, Li Z, Sun C, Hsu YC, Liang H, Basser P. Feasibility of filter-exchange imaging (FEXI) in measuring different exchange processes in human brain. Neuroimage. 2020 Oct 1;219:117039. doi: 10.1016/j.neuroimage.2020.117039. Epub 2020 Jun 10.
- Background Batra A, Latour LL, Ruetzler CA, Hallenbeck JM, Spatz M, Warach S, Henning EC. Increased plasma and tissue MMP levels are associated with BCSFB and BBB disruption evident on post-contrast FLAIR after experimental stroke. J Cereb Blood Flow Metab. 2010 Jun;30(6):1188-99. doi: 10.1038/jcbfm.2010.1. Epub 2010 Mar 3.
- Background Koh SX, Lee JK. S100B as a marker for brain damage and blood-brain barrier disruption following exercise. Sports Med. 2014 Mar;44(3):369-85. doi: 10.1007/s40279-013-0119-9.
- Background El Amki M, Gluck C, Binder N, Middleham W, Wyss MT, Weiss T, Meister H, Luft A, Weller M, Weber B, Wegener S. Neutrophils Obstructing Brain Capillaries Are a Major Cause of No-Reflow in Ischemic Stroke. Cell Rep. 2020 Oct 13;33(2):108260. doi: 10.1016/j.celrep.2020.108260.
- Background Stoll G, Nieswandt B. Thrombo-inflammation in acute ischaemic stroke - implications for treatment. Nat Rev Neurol. 2019 Aug;15(8):473-481. doi: 10.1038/s41582-019-0221-1. Epub 2019 Jul 1.
- Background Kollikowski AM, Schuhmann MK, Nieswandt B, Mullges W, Stoll G, Pham M. Local Leukocyte Invasion during Hyperacute Human Ischemic Stroke. Ann Neurol. 2020 Mar;87(3):466-479. doi: 10.1002/ana.25665. Epub 2020 Jan 16.
- Background El Amki M, Wegener S. Improving Cerebral Blood Flow after Arterial Recanalization: A Novel Therapeutic Strategy in Stroke. Int J Mol Sci. 2017 Dec 9;18(12):2669. doi: 10.3390/ijms18122669.
- Background Bustamante A, Ning M, Garcia-Berrocoso T, Penalba A, Boada C, Simats A, Pagola J, Ribo M, Molina C, Lo E, Montaner J. Usefulness of ADAMTS13 to predict response to recanalization therapies in acute ischemic stroke. Neurology. 2018 Mar 20;90(12):e995-e1004. doi: 10.1212/WNL.0000000000005162. Epub 2018 Feb 14.
- Background Gragnano F, Sperlongano S, Golia E, Natale F, Bianchi R, Crisci M, Fimiani F, Pariggiano I, Diana V, Carbone A, Cesaro A, Concilio C, Limongelli G, Russo M, Calabro P. The Role of von Willebrand Factor in Vascular Inflammation: From Pathogenesis to Targeted Therapy. Mediators Inflamm. 2017;2017:5620314. doi: 10.1155/2017/5620314. Epub 2017 May 28.
- Background Nieswandt B, Kleinschnitz C, Stoll G. Ischaemic stroke: a thrombo-inflammatory disease? J Physiol. 2011 Sep 1;589(17):4115-23. doi: 10.1113/jphysiol.2011.212886. Epub 2011 Jul 18.
- Background Kraft P, Gob E, Schuhmann MK, Gobel K, Deppermann C, Thielmann I, Herrmann AM, Lorenz K, Brede M, Stoll G, Meuth SG, Nieswandt B, Pfeilschifter W, Kleinschnitz C. FTY720 ameliorates acute ischemic stroke in mice by reducing thrombo-inflammation but not by direct neuroprotection. Stroke. 2013 Nov;44(11):3202-10. doi: 10.1161/STROKEAHA.113.002880. Epub 2013 Sep 12.
- Background Schuhmann MK, Guthmann J, Stoll G, Nieswandt B, Kraft P, Kleinschnitz C. Blocking of platelet glycoprotein receptor Ib reduces "thrombo-inflammation" in mice with acute ischemic stroke. J Neuroinflammation. 2017 Jan 21;14(1):18. doi: 10.1186/s12974-017-0792-y.
- Background Takagi T, Hara H. Protective effects of cilostazol against hemorrhagic stroke: Current and future perspectives. J Pharmacol Sci. 2016 Jul;131(3):155-61. doi: 10.1016/j.jphs.2016.04.023. Epub 2016 May 3.
- Background Horai S, Nakagawa S, Tanaka K, Morofuji Y, Couraud PO, Deli MA, Ozawa M, Niwa M. Cilostazol strengthens barrier integrity in brain endothelial cells. Cell Mol Neurobiol. 2013 Mar;33(2):291-307. doi: 10.1007/s10571-012-9896-1. Epub 2012 Dec 7.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Cilostazol | Small molecule | 25 mg | Other |
| Comparator | Dexborneol | Small molecule | 6 mg | Other |