Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Bath, Philip M.W.; Christensen, L M; Woodhouse, Lisa J.; Bentsen, L; Appleton, Jason P.; Krarup Hansen, C; Beridze, M.; Thomsen, T T; Christensen, Hanne; Kruuse, C; Dineen, Robert A.; Jensen, H H; Duley, Lelia; Hansen, S S; England, Timothy J.; Petrovic, V; Flaherty, Katie; Beridze, N; Havard, Diane; Kakabadze, N; Heptinstall, Stan; Kherkheulidze, T; James, Marilyn; Kakabadze, D; Krishnan, Kailash; Toidze, I; Markus, H.S.; Lobjanidze, N; Montgomery, Alan A.; Akiashvili, N; Pocock, Stuart J.; ATevdoradze; Randall, Marc; Khizanishvili, N; Ranta, A.; Tsanava, T; Robinson, Thompson G.; Taylor, R; Scutt, Polly; Iniesta, I; Venables, Graham S.; Kok, J; Sprigg, Nikola; Duignan, J; Funnell, M; Cariga, P; Rodriguez, M; Watson, I J; Tennant, S; Macleod, M; Furnace, J; Gow, H; Irvine, J; Joyson, A; Nelson, S; Taylor, V; Smith, M; Bellfield, R; Hairsine, B; Davies, R; Dodd, A; Corrigan, J; Doherty, M; Ahmed, A; Denniss, C; Johnson-Holland, S; Kay, K A; Icart Palau, R; Auld, G; Daboo, P; Erande, R; Grimwood, G; Hove, D; Howaniec, L; Redjep, O; Rangasamay, R; Butt, G; Sandler, D; Reddan, J; Stafford, S; McIlmoyle, J; Maguire, S; Murphy, P; Chambers, J; Guthrie, L; Osborn, M; Steele, A; Burn, M; Benford, A; Misra, A; Hilton, D; O'Brien, E; Amis, E; Finlay, S; Mitchell, J; Geraghty, O; Harvey, K; Hazel, B; Mashate, S; Wilding, P; Sajid, M; Ball, M; Gascoyne, R; Sivakumar, R; Wright, A; Chatterjee, K; Booth, S; Eccleson, H; Kelly, C; Leason, S; Perkins, C; Bruce, D; Brown, E; Clayton, S; Garside, M; Rogers, G; Lawrence, E; Mahmood, S; Watchurst, C; Chadha, D; Glover, L; Holford, L; Smith, K; Walstow, D; Williams, R; O'Shea, L; Goodsell, J; Athulathmudali, C; Barbon, E; Namushi, R; Jacob, P; Johnson, L; Morse, D; McGhee, C; Speirs, O; Atkinson, S; Peacocke, A; Langhorne, P; Graham, R; Wright, F; McAlpine, C; Ravindrane, A; Bajoriene, M; Matter, L; Windebank, S; Giallombardo, E; Dellafera, D; Eglinton, C; Wilson, J; Broughton, D; Chapman, K; Dixon, L; Zaidi, M; Ayes, K; Kessell, J; Manawadu, D; Adegbaju, O; Aeron-Thomas, J; Anderson, K; Brigden, A; Cattermole, E; Good, J; Hassan, S; Khoromana, E; Lee-Carbon, L; Marks, K; Mckenzie, E; Sikondari, N; Cooper, M; Whysall, K; Wynter, I; Bamford, J; Hassan, A; Wanklyn, P; Kambafwile, M; Makawa, L; Waugh, D; Veraque, E; Soliman, M G G; Arif, S; Brown, R; Butler, S; Hewitt, C; Hindle, J; Pusalkar, A; Beadle, H; Chan, K; Siddiqui, M; Dangri, P; Buddha, S; Asokanathan, A; Mistri, A; Eveson, D; Musarrat, K; Manning, L; Anand, S; Christian, P; Khan, S; Patel, C; Sein, M; Banns, J; Gibson, E; Gordon, T; Gruenbeck, Y; Wong, S; Datta, P; Bateman, G; Jackson, L; Needle, A; Duodu, Y; Oliver, R; Padilla-Harris, C; Barber, M; Esson, D; Brodie, F; McInnes, C; Fotherby, K; Butler, D; Morgan, D; Preece, K; Willberry, A; Dent, M; Hammonds, F; Hunt, J; Vernon, C; O'Kane, D; Faola, F; Lai, P; O'Callaghan, J; Smith, C; Price, C; Lakey, R; Riddell, V; Smith, A; Storey, G; Munshi, S; Buck, A; Clarke, J; Gilzeane, N; Godfrey, M; Keshvara, R; Richardson, C; Roffe, J; Ryan, L; Shelton, F; Sunman, W; Tittle, A; Tomlinson, J; Whittamore, K; Wilkes, G; Owusu-Agyei, P; Temple, N; Mangion, D; Hardwick, A; Netherton, K; MohdNor, A; Hyams, B; Norman, S; Persad, N; Ragab, S; Dickson, C; Dube, J; Jinks, E; Knops, K; Wadams, B; Ali, K; Gaylard, J; Spurling, G; Sztriha, L; Ajao, T; Alao, M; KChan, F; Webster, P; HowardT JDobson, P; Hyatt, L; Sims, D; Cunningham, J; Esisi, B; Cassidy, T; Bokhari, M; McClelland, B; Mokoena, B; Gunathilagan, G; Jones, S; Reader, M; Thomas, G; Tilby, S; Findlay, P; Barrett, F; Leslie, F; Ross, S; Shread, I; Okwera, J; Howe, J; Harrington, F; Courtauld, G; Schofield, C; Donnelly, R; Maddula, M; Scott, J; Beavan, J; Muhidden, K; Memon, I; Clarke, M; Hedstrom, A; Mills, L; Hemsley, A; Bowring, A; Boxall, L; Kingwell, H; Keenan, S; Roughan, C; Manoj, A; Cox, P; Fletcher, G; Lopez, P; Emsley, H; Gregary, B; McLoughlin, A; Raj, S; Roffe, C; Abano, N; Barry, A; Butler, A; Carpio, R; Castro, K; Finney, K; Gomm, S; Hiden, J; Grocott, J; Lyjko, S; Maguire, H; Remegoso, A; Sanyal, R; Stevens, S; Natarajan, I; Chembala, J; Muddegowda, G; Warusevitane, A; Blight, A; Balazikova, O; Lawlor, C; Shaw, L; Button, D; Howcroft, D; Lucas, S; Madigan, B; McCann, S; Dixit, A; Barkat, A; Davis, J; Fawcett, M; Finlay, L; Guy, H; Hays, C; Hogg, V; Horsley, E; Hubbuck, C; Pringle, C; Stevenson, C; Storey, K; Thompson, T; Woodward, S; Banerjee, A; Allcock, C; Merotra, S; Douglass, C; Campbell, E; Jarapa, R; Johnes, M; Keaveney, C; Marsden, T; Naing, Z; Perez, J; Shaw, K; Black, T; Anthony, A; Clarke, C; Paterson, J; Deighton, K; Temlett, E; Blank, C; Doyle, C; Duty, S; Gill, K; Harkness, K; Kamara, C; Richards, E; Elfandi, K; Guyler, P; Harman, P; Khuoge, C; Kunhunny, S; Tysoe, S; Moynihan, B; Adedoyin, T; Chopra, N; Dayal, N; Ghatala, R; Jeyaraj, N; Jones, I; Kennedy, F; Kerin, L; Khanom, N; Lewis, S; Maheswaran, S; Montague, L; Niemierko, M; O'Reilly, J; Trippier, S; Watson, F; Wilkinson, P; Young, E; Dizayee, K; Cochrane, H; O'Connell, J; Mokoena, L; Osborne, E; Nair, A; Greig, J; Jenkins, C; Powell, J; Price, F; Chowdhury, M; Brixey, S; Hunt, L; Rands, N; Rose, G; Stoddart, S; Srinivasan, M; Motherwell, N; Shekhar, R; Fuller, T; Lankester, A; Lingwood, P; Rankin, C; Webb, H; Jupp, B; Bell, J; Hann, G; Longland, B; Ovington, C; Bhaskaran, B; Ayres, G; Bailey, C; Bearne, H; Buxton, J; Fitzell, P; Hilaire, C; Kelly, D; Szabo, S; Tomlin, D; Gamble, E; Charles, B; Kumar, R; Fluskey, T; Mellor, Z; Peters, J; Sutton, V; Kenton, A; Martin, I; Nyabadza, S; Ghosh, S; Henry, M; Kumar, B; Bruce, D; Ambulo, C; Crawford, S; Nozedar, T; Platton, M; Cvoro, V; Couser, M; McCormick, K; Wilkinson, D; Javaid, K; Hurdowar, S; Attygalle, T; Sundayi, S; Orugun, O; Crowther, H; Jolly, R; Poultney, U; Azim, A; Krasinska-Chavez, M; White, J; Sengupta, N; Margalef, J; Metiu, M G; Meenakshisundaram, S; Dealing, S; Hargroves, D; Beranova, E; Cowie, L; Rudenko, H; Thomson, A; Verrion, A; Rashed, K; Board, S; Buckley, C; Hayward, D; Jenkins, K; Keeling, E; Rowland-Axe, R; Vickers, C; Wood, D; Lehman, A; Erande, R; Patel, M; Russell, H; Rehman, H; Forrest, D; Farren, P

doi:10.1016/S0140-6736(17)32849-0

Endovascular Thrombectomy vs Best Medical Therapy for Late Presentation Acute Ischaemic Stroke with Proximal Large Vessel Occlusion Selected Based on Non-Contrast CT: A Retrospective Analysis of Two Prospectively Defined Cohorts (2022)
Journal Article
Singh Dhillon, P., Butt, W., Jovin, T. G., Podlasek, A., McConachie, N., Lenthall, R., …England, T. J. (2023). Endovascular Thrombectomy vs Best Medical Therapy for Late Presentation Acute Ischaemic Stroke with Proximal Large Vessel Occlusion Selected Based on Non-Contrast CT: A Retrospective Analysis of Two Prospectively Defined Cohorts. Stroke: Vascular and Interventional Neurology, 3(2), Article e000686. https://doi.org/10.1161/SVIN.122.000686

Background: The efficacy and safety of endovascular thrombectomy (EVT) beyond 6 hours from acute ischaemic stroke (AIS) onset for patients selected without CT perfusion or MR imaging is undetermined in routine clinical practice. Methods: In this... Read More about Endovascular Thrombectomy vs Best Medical Therapy for Late Presentation Acute Ischaemic Stroke with Proximal Large Vessel Occlusion Selected Based on Non-Contrast CT: A Retrospective Analysis of Two Prospectively Defined Cohorts.

Effect of Tranexamic Acid Administration on Remote Cerebral Ischemic Lesions in Acute Spontaneous Intracerebral Hemorrhage: A Substudy of a Randomized Clinical Trial (2022)
Journal Article
Pszczolkowski, S., Sprigg, N., Woodhouse, L. J., Gallagher, R., Swienton, D., Law, Z. K., …Dineen, R. A. (2022). Effect of Tranexamic Acid Administration on Remote Cerebral Ischemic Lesions in Acute Spontaneous Intracerebral Hemorrhage: A Substudy of a Randomized Clinical Trial. JAMA Neurology, 79(5), 468-477. https://doi.org/10.1001/jamaneurol.2022.0217

Importance: Hyperintense foci on diffusion-weighted imaging (DWI) that are spatially remote from the acute hematoma occur in 20% of people with acute spontaneous intracerebral hemorrhage (ICH). Tranexamic acid, a hemostatic agent that is under invest... Read More about Effect of Tranexamic Acid Administration on Remote Cerebral Ischemic Lesions in Acute Spontaneous Intracerebral Hemorrhage: A Substudy of a Randomized Clinical Trial.

Association between time to treatment and clinical outcomes in endovascular thrombectomy beyond 6 hours without advanced imaging selection (2022)
Journal Article
Dhillon, P. S., Butt, W., Podlasek, A., McConachie, N., Lenthall, R., Nair, S., …England, T. J. (2023). Association between time to treatment and clinical outcomes in endovascular thrombectomy beyond 6 hours without advanced imaging selection. Journal of NeuroInterventional Surgery, 15(4), 336-342. https://doi.org/10.1136/neurintsurg-2021-018564

Background: The effectiveness and safety of endovascular thrombectomy (EVT) in the late window (6-24 hours) for acute ischemic stroke (AIS) patients selected without advanced imaging is undetermined. We aimed to assess clinical outcomes and the relat... Read More about Association between time to treatment and clinical outcomes in endovascular thrombectomy beyond 6 hours without advanced imaging selection.

Endovascular thrombectomy beyond 24 hours from ischemic stroke onset: A propensity score matched cohort study (2022)
Journal Article
Singh Dhillon, P., Butt, W., Podlasek, A., Barrett, E., McConachie, N., Lenthall, R., …England, T. J. (2023). Endovascular thrombectomy beyond 24 hours from ischemic stroke onset: A propensity score matched cohort study. Journal of NeuroInterventional Surgery, 15(3), 233-237. https://doi.org/10.1136/neurintsurg-2021-018591

Background: The safety and functional outcome of endovascular thrombectomy (EVT) in the very late (VL; >24 hours) time window from ischemic stroke onset remains undetermined. Methods: Using data from a national stroke registry, we used propensity sco... Read More about Endovascular thrombectomy beyond 24 hours from ischemic stroke onset: A propensity score matched cohort study.

Brief Consent Methods Enable Rapid Enrollment in Acute Stroke Trial: Results From the TICH-2 Randomized Controlled Trial (2021)
Journal Article
the TICH-2 Investigators, Law, Z. K., Appleton, J. P., Scutt, P., Roberts, I., Al-Shahi Salman, R., …Sprigg, N. (2021). Brief Consent Methods Enable Rapid Enrollment in Acute Stroke Trial: Results From the TICH-2 Randomized Controlled Trial. Stroke, 53(4), 1141-1148. https://doi.org/10.1161/STROKEAHA.121.035191

Background: Seeking consent rapidly in acute stroke trials is crucial as interventions are time sensitive. We explored the association between consent pathways and time to enrollment in the TICH-2 (Tranexamic Acid in Intracerebral Haemorrhage-2) rand... Read More about Brief Consent Methods Enable Rapid Enrollment in Acute Stroke Trial: Results From the TICH-2 Randomized Controlled Trial.

Predictors and outcomes of neurological deterioration in intracerebral hemorrhage: results from the TICH-2 randomised controlled trial (2020)
Journal Article
Kang Law, Z., Dineen, R., England, T. J., Cala, L., Mistri, A. K., Appleton, J. P., …TICH-2 investigators. (2021). Predictors and outcomes of neurological deterioration in intracerebral hemorrhage: results from the TICH-2 randomised controlled trial. Translational Stroke Research, 12, 275-283. https://doi.org/10.1007/s12975-020-00845-6

Neurological deterioration is common after intracerebral hemorrhage (ICH). We aimed to identify the predictors and effects of neurological deterioration and whether tranexamic acid reduced the risk of neurological deterioration. Data from the Tranexa... Read More about Predictors and outcomes of neurological deterioration in intracerebral hemorrhage: results from the TICH-2 randomised controlled trial.

Incidence and predictors of early seizures in intracerebral haemorrhage and the effect of tranexamic acid (2020)
Journal Article
Law, Z. K., England, T. J., Mistri, A. K., Woodhouse, L. J., Cala, L., Dineen, R., …TICH-2 investigators. (2020). Incidence and predictors of early seizures in intracerebral haemorrhage and the effect of tranexamic acid. European Stroke Journal, 5(2), 123-129. https://doi.org/10.1177/2396987320901391

Introduction: Seizures are common after intracerebral haemorrhage. Tranexamic acid increases the risk of seizures in non-intracerebral haemorrhage population but its effect on post-intracerebral haemorrhage seizures is unknown. We explored the risk f... Read More about Incidence and predictors of early seizures in intracerebral haemorrhage and the effect of tranexamic acid.

Triple versus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: The TARDIS RCT (2018)
Journal Article
Bath, P. M., Woodhouse, L. J., Appleton, J. P., Beridze, M., Christensen, H., Dineen, R. A., …Sprigg, N. (2018). Triple versus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: The TARDIS RCT. Health Technology Assessment, 22(48), 1-75. https://doi.org/10.3310/hta22480

© Queen’s Printer and Controller of HMSO 2018. Background: Two antiplatelet agents are better than one for preventing recurrent stroke after acute ischaemic stroke or transient ischaemic attack (TIA). Therefore, intensive treatment with three agents... Read More about Triple versus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: The TARDIS RCT.

Does tranexamic acid lead to changes in MRI-measures of brain tissue health in patients with spontaneous intracerebral haemorrhage? An MRI sub-study nested within the double-blind randomised controlled TICH-2 trial (2018)
Journal Article
Dineen, R. A., Pszczolkowski, S., Flaherty, K., Law, Z. K., Morgan, P. S., Roberts, I., …Sprigg, N. (in press). Does tranexamic acid lead to changes in MRI-measures of brain tissue health in patients with spontaneous intracerebral haemorrhage? An MRI sub-study nested within the double-blind randomised controlled TICH-2 trial. BMJ Open, 8(2), Article e019930. https://doi.org/10.1136/bmjopen-2017-019930

Objectives: To test whether administration of the antifibrinolytic drug tranexamic acid (TXA) in patients with spontaneous intracerebral haemorrhage (SICH) leads to increased prevalence of diffusion-weighted MRI defined hyperintense ischaemic lesions... Read More about Does tranexamic acid lead to changes in MRI-measures of brain tissue health in patients with spontaneous intracerebral haemorrhage? An MRI sub-study nested within the double-blind randomised controlled TICH-2 trial.

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial (2017)
Journal Article
Bath, P. M., Christensen, L. M., Woodhouse, L. J., Bentsen, L., Appleton, J. P., Krarup Hansen, C., …Farren, P. (2018). Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial. Lancet, 391(10123), 850-859. https://doi.org/10.1016/S0140-6736%2817%2932849-0

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplat... Read More about Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial.

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