Fibrinogen Replacement to Prevent Intracranial Haemorrhage in Ischemic Stroke Patients After Thrombolysis (FibER)

Summary

Fibrinogen replacement could prevent haemorrhagic complications in ischemic stroke patients with secondary post-rtPA hypofibrinogenemia

Timeline

Start

2022-02-08

Primary completion

2024-12-31

Completion

2025-05-27

Publications

• Background Whiteley WN, Emberson J, Lees KR, 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 MG, Lindley RI, Lyden P, Olivot JM, Parsons M, Toni D, Toyoda K, Wahlgren N, Wardlaw J, Del Zoppo GJ, Sandercock P, Hacke W, Baigent C; Stroke Thrombolysis Trialists' Collaboration. Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis. Lancet Neurol. 2016 Aug;15(9):925-933. doi: 10.1016/S1474-4422(16)30076-X. Epub 2016 Jun 8.
• Background Lansberg MG, Albers GW, Wijman CA. Symptomatic intracerebral hemorrhage following thrombolytic therapy for acute ischemic stroke: a review of the risk factors. Cerebrovasc Dis. 2007;24(1):1-10. doi: 10.1159/000103110. Epub 2007 May 22.
• Background Trouillas P, von Kummer R. Classification and pathogenesis of cerebral hemorrhages after thrombolysis in ischemic stroke. Stroke. 2006 Feb;37(2):556-61. doi: 10.1161/01.STR.0000196942.84707.71. Epub 2006 Jan 5.
• Background Francis CW, Kornberg A. Fibrinogen- and fibrin-degradation products during fibrinolytic therapy. Ann N Y Acad Sci. 1992 Dec 4;667:310-23. doi: 10.1111/j.1749-6632.1992.tb51632.x. No abstract available.
• Background Tanne D, Kasner SE, Demchuk AM, Koren-Morag N, Hanson S, Grond M, Levine SR. Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey. Circulation. 2002 Apr 9;105(14):1679-85. doi: 10.1161/01.cir.0000012747.53592.6a.
• Background Vandelli L, Marietta M, Gambini M, Cavazzuti M, Trenti T, Cenci MA, Casoni F, Bigliardi G, Pentore R, Nichelli P, Zini A. Fibrinogen decrease after intravenous thrombolysis in ischemic stroke patients is a risk factor for intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2015 Feb;24(2):394-400. doi: 10.1016/j.jstrokecerebrovasdis.2014.09.005. Epub 2014 Dec 11.
• Background Matosevic B, Knoflach M, Werner P, Pechlaner R, Zangerle A, Ruecker M, Kirchmayr M, Willeit J, Kiechl S. Fibrinogen degradation coagulopathy and bleeding complications after stroke thrombolysis. Neurology. 2013 Mar 26;80(13):1216-24. doi: 10.1212/WNL.0b013e3182897015. Epub 2013 Mar 13.
• Background Sun X, Berthiller J, Trouillas P, Derex L, Diallo L, Hanss M. Early fibrinogen degradation coagulopathy: a predictive factor of parenchymal hematomas in cerebral rt-PA thrombolysis. J Neurol Sci. 2015 Apr 15;351(1-2):109-114. doi: 10.1016/j.jns.2015.02.048. Epub 2015 Mar 6.
• Background Yaghi S, Boehme AK, Dibu J, Leon Guerrero CR, Ali S, Martin-Schild S, Sands KA, Noorian AR, Blum CA, Chaudhary S, Schwamm LH, Liebeskind DS, Marshall RS, Willey JZ. Treatment and Outcome of Thrombolysis-Related Hemorrhage: A Multicenter Retrospective Study. JAMA Neurol. 2015 Dec;72(12):1451-7. doi: 10.1001/jamaneurol.2015.2371.
• Background Yaghi S, Willey JZ, Cucchiara B, Goldstein JN, Gonzales NR, Khatri P, Kim LJ, Mayer SA, Sheth KN, Schwamm LH; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; and Council on Quality of Care and Outcomes Research. Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2017 Dec;48(12):e343-e361. doi: 10.1161/STR.0000000000000152. Epub 2017 Nov 2.
• Background Weiss G, Lison S, Glaser M, Herberger S, Johanning K, Strasser T, Huber T, Spannagl M, Heindl B. Observational study of fibrinogen concentrate in massive hemorrhage: evaluation of a multicenter register. Blood Coagul Fibrinolysis. 2011 Dec;22(8):727-34. doi: 10.1097/MBC.0b013e32834cb343.
• Background Fenger-Eriksen C, Lindberg-Larsen M, Christensen AQ, Ingerslev J, Sorensen B. Fibrinogen concentrate substitution therapy in patients with massive haemorrhage and low plasma fibrinogen concentrations. Br J Anaesth. 2008 Dec;101(6):769-73. doi: 10.1093/bja/aen270. Epub 2008 Sep 25.
• Background Fassl J, Lurati Buse G, Filipovic M, Reuthebuch O, Hampl K, Seeberger MD, Bolliger D. Perioperative administration of fibrinogen does not increase adverse cardiac and thromboembolic events after cardiac surgery. Br J Anaesth. 2015 Feb;114(2):225-34. doi: 10.1093/bja/aeu364. Epub 2014 Oct 16.
• Background Wikkelso A, Lunde J, Johansen M, Stensballe J, Wetterslev J, Moller AM, Afshari A. Fibrinogen concentrate in bleeding patients. Cochrane Database Syst Rev. 2013 Aug 29;2013(8):CD008864. doi: 10.1002/14651858.CD008864.pub2.
• Background Vandelli L, Marietta M, Trenti T, Varani M, Bigliardi G, Rosafio F, Dell'acqua ML, Picchetto L, Nichelli P, Zini A. Fibrinogen concentrate replacement in ischemic stroke patients after recombinant tissue plasminogen activator treatment. Adv Clin Exp Med. 2019 Feb;28(2):219-222. doi: 10.17219/acem/84936.
• Zini A, Vandelli L, Forlivesi S, Merli E, Migliaccio L, Gentile L, Romoli M, Baccari F, Sebastiani M, Nonino F, Cevoli S, Bigliardi G. Fibrinogen replacement to prevent intracranial hemorrhage in ischemic stroke patients after thrombolysis - a prospective randomized open blinded endpoint trial (FibER): rationale and methods. J Stroke Cerebrovasc Dis. 2026 Mar;35(3):108572. doi: 10.1016/j.jstrokecerebrovasdis.2026.108572. Epub 2026 Jan 23.

Drugs

Indications