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

NCT05300672 | Completed Phase 3

• 2 other identifiers: 1123-2020-FARM-AUSLBO2020-005242-41
• Study Type: interventional
• Target: 207
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Intracranial Hemorrhages; Ischemic Stroke

Keywords

Intracranial Hemorrhages; Ischemic Stroke; Fibrinogen replacement; Thrombolysis

Outcome Measures

Primary Outcomes (1)

• Intracranial hemorrhage defined as parenchymal hematoma

  Change in combined rate of parenchymal hematomas within the infarct area (PH1, PH2) or remote from the actual infarct (rPH1, rPH2), either asymptomatic or symptomatic (according to the NINDS, ECASS and SITS classification) documented on the brain CT scan after 24 hours from rtPA infusion, or before in case of clinical worsening, and at day 7 (or at the discharge if before).

  7 days after randomization

Secondary Outcomes (2)

• Symptomatic intracranial hemorrhage

  7 days after randomization

• Extracranial bleedings

  7 days after randomization

Other Outcomes (5)

• Serious thromboembolic adverse events

  7 days after randomization

• National Institutes of Health Stroke Scale (NIHSS)

  7 days after randomization

• Modified Rankin Scale (mRS)

  3 months after randomization

Study Arms (2)

fibrinogen infusion

EXPERIMENTAL

fibrinogen infusion (2 g) in stroke patients with secondary post-rtPA hypofibrinogenemia

Drug: fibrinogen infusion

No fibrinogen infusion

NO INTERVENTION

No fibrinogen infusion

Interventions

fibrinogen infusion DRUG

fibrinogen infusion (2 g) in stroke patients with secondary post-rtPA hypofibrinogenemia

fibrinogen infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with acute ischemic stroke treated with i.v. thrombolysis (rtPA 0,9 mg/Kg, 10% in bolus and 90% in infusion in 60 minutes)
• age \>18 years
• critical hypofibrinogenemia post-tPA, defined as a decrease of serum fibrinogen level \<200 mg/dl and/or a rate decrease \>50% than baseline level
• written informed consent

You may not qualify if:

• contraindication to rtPA treatment;
• patients who present symptomatic ICH during infusion of rt-PA,
• absence of written informed consent

Sponsors & Collaborators

• Azienda Usl di Bologna: lead
• Ministero della Salute, Italy: collaborator

Study Sites (1)

IRCCS Istituto delle Scienze Neurologiche di Bologna

Bologna, Italy

Location

Related Publications (16)

• 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.

  PMID: 27289487 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.

  PMID: 17519538 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.

  PMID: 16397182 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.

  PMID: 1309052 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.

  PMID: 11940547 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.

  PMID: 25497721 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.

  PMID: 23486872 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.

  PMID: 25783009 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.

  PMID: 26501741 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.

  PMID: 29097489 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.

  PMID: 22024795 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.

  PMID: 18818192 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.

  PMID: 25324348 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.

  PMID: 23986527 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.

  PMID: 30507073 BACKGROUND

• 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 Jan 23:108572. doi: 10.1016/j.jstrokecerebrovasdis.2026.108572. Online ahead of print.

  PMID: 41581534 DERIVED

MeSH Terms

Conditions

Intracranial Hemorrhages; Ischemic Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Stroke

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: blinded-endpoint (PROBE)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: This is a pilot, phase 3, prospective randomized open label, blinded-endpoint (PROBE) controlled trial on the effect of fibrinogen infusion in acute ischemic stroke patients treated with i.v. rtPA who develop hypofibrinogenemia (fibrinogen\<2 g/L or decrease rate \>50% after 2 and 6 hours from iv rtPA, compared to baseline values

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: March 29, 2022
• Study Start: February 8, 2022
• Primary Completion: December 31, 2024
• Study Completion: May 27, 2025
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)