Intracranial HemorrhagesPhase 3FibERNCT05300672
Fibrinogen Replacement to Prevent Intracranial Haemorrhage in Ischemic Stroke Patients After Thrombolysis (FibER)
A Phase 3 study testing fibrinogen infusion in people with Intracranial Hemorrhages and Ischemic Stroke, run by Azienda Usl di Bologna at 1 site in Italy.
Trial summary
Fibrinogen replacement could prevent haemorrhagic complications in ischemic stroke patients with secondary post-rtPA hypofibrinogenemia Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intracranial Hemorrhages, Ischemic Stroke
- What is being tested?
- fibrinogen infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 207 participants
- Where
- 1 siteItaly
- Study dates
- 8 Feb 2022to 27 May 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- contraindication to rtPA treatment;
- patients who present symptomatic ICH during infusion of rt-PA,
- absence of written informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Fibrinogen Replacement to Prevent Intracranial Haemorrhage in Ischemic Stroke Patients After Thrombolysis: a Pilot Probe Randomized Controlled Trial (FibER)
Fibrinogen replacement could prevent haemorrhagic complications in ischemic stroke patients with secondary post-rtPA hypofibrinogenemia
Read the detailed description
Intravenous recombinant tissue plasminogen activator (rtPA) is the first recommended reperfusion therapy for acute ischemic stroke, as well as endovascular treatment in case of large vessel occlusion, but it increases the risk of ICH.
The pathophysiological mechanisms of ICH after i.v. thrombolysis in ischemic stroke is complex: hyperglycemia, early ischemic changes on neuroimaging, clinical stroke severity assessed by the National Institutes of Health Stroke Scale score (NIHSS) on admission, advanced age and high blood pressure are known risk factors for hemorrhagic cerebral transformations. The risk of bleeding is likely mediated by coagulopathy, reperfusion injury, and breakdown of blood-brain barrier.
The rtPA binds the plasminogen within the clot, converting it to plasmin, a proteolytic enzyme capable to dissolve the clot. However plasmin activity is not specific for clot-associated fibrin, but also breaks down other circulating proteins, including fibrinogen. An early fibrinogen degradation coagulopathy can occur after i.v. thrombolysis, that could be implicated in bleeding complications.
In 2002, it was shown how high levels of fibrin and fibrinogen degradation factors at 2 hours after rtPA could be a risk factor for early ICH.
Few years ago, the investigators published a work demonstrating that an early decrease in fibrinogen levels is a risk factor for ICH within the first 24 hours and 7 days after rtPA therapy in ischemic stroke patients. In this experience, the investigators collected data about ischemic stroke patients that experienced a severe hypofibrinogenemia after 2 hours from iv rtPA. All patient were treated with fibrinogen replacement, fibrinogen infusion was well tolerated, without any thrombotic complication, and the infusion of fibrinogen did not reduce the rate of recanalization and, therefore, did not negatively affect the chances of reopening the occluded vessel. These data agree with another study showing that prominent fibrinogen turnover after thrombolysis is a relevant cause of major bleeding complications, and specifically that a decrease >200 mg/dL in the fibrinogen level 6 hours after thrombolysis emerges as a significant and independent predictor for bleeding risk. Morover, other authors confirmed that the decrease of fibrinogen level less than 2 g/L in the first 2 hours after thrombolysis multiplies the odds of early parenchymal hematoma (PH) by a factor of 12.82 . Similarly, a large study about symptomatic intracerebral haemorrhage (sICH) showed that severe hypofibrinogenemia (<150 mg/dL) was associated with ICH expansion.
The correction of the coagulopathy after rtPA remained the mainstay of treatment for sICH after
thrombolysis, but no specific agent has been shown to be most effective. Data from other disease states, however, raise the possibility that certain agents not routinely used, may be effective. As regard, in the consensus statement of 2017, American Heart Association Stroke (AHA) Council investigated possible treatments for sICH after rtPA in ischemic stroke patients, evaluating the role of cryoprecipitate, prothrombin complex concentrate, fresh frozen plasma, antifibrinolytic agents, platelets, Factor VI and vit. K. In particular, infusion of cryoprecipitate was suggested because it contains fibrinogen, that corrects dysfibrinogenemia. In particular, if sICH is diagnosed, physicians were recommended to consider immediately sending a blood sample for fibrinogen level and empirically transfusing with 10 U cryoprecipitate and anticipate giving more cryoprecipitate as needed to achieve a fibrinogen level of >150 mg/dL.
Indeed, several studies in other different medical fields, suggested fibrinogen supplementation with anti- haemorrhagic purposes in patients with severe haemorrhages and related fibrinogen deficiency, following trauma and surgery.
The investigators had previously analysed the trend of fibrinogen decrease after i.v. rtPA in 56 ischemic patients taking fibrinogen dosage at 2, 6, 12 and 24 hours from rtPA infusion: fibrinogen level drops within the first 2 hours and then slowly increases in the following 24 hours, still being lower than basal fibrinogen value. Dividing patients in two subgroups according to pre-rtPA fibrinogen level, a higher baseline fibrinogen resulted in higher risk of deep decrease in fibrinogen value. Medical literature about the rate of thrombotic complication after fibrinogen concentrate administration in stroke patients is relatively lacking. However, experiences in cardiac surgery showed that administration of fibrinogen concentrate was not associated with an increased risk of mortality and thromboembolic events, and a recent Cochrane review on fibrinogen concentrate in bleeding patients, did not show any adverse events such as thrombotic episodes following the use of fibrinogen concentrate.
In a pilot experience, the investigators administrated i.v. fibrinogen in 39 patients with severe hypofibrinogenemia after 2 hours from i.v. rtPA. Fibrinogen infusion was well tolerated: no thrombotic complications occurred in 37 out of 39 patients (94.77%). Two patients developed pulmonary embolism, of which 1 was only segmental and 1 in an active cancer patient. Moreover fibrinogen replacement did not reduce the rate of recanalization, so it did not negatively affect the chances of reopening the occluded vessel.
- Conditions
- Intracranial Hemorrhages, Ischemic Stroke
- Being tested
- fibrinogen infusion
- Keywords
- Intracranial Hemorrhages, Ischemic Stroke, Fibrinogen replacement, Thrombolysis
- Medical subject headings
- Intracranial Hemorrhages, Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fibrinogen infusionDrug
fibrinogen infusion (2 g) in stroke patients with secondary post-rtPA hypofibrinogenemia
| Study group | Role | What they receive |
|---|---|---|
| fibrinogen infusion | Experimental | fibrinogen infusion (2 g) in stroke patients with secondary post-rtPA hypofibrinogenemia Receives: Drug: fibrinogen infusion |
| No fibrinogen infusion | No intervention | No fibrinogen infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 7 days after randomization
Secondary outcomes (2)
Symptomatic intracranial hemorrhage
Number of participants who develop symptomatic intracranial hemorrhage (sICH) according to NINDS, ECASS and SITS classifications.
Measured: 7 days after randomization
Extracranial bleedings
Number of participants who develop any extracranial bleedings.
Measured: 7 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2022
- Study start8 Feb 2022
- Primary completion31 Dec 2024
- Study completion27 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Intracranial HemorrhagesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 207 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Usl di Bologna
- Sponsor type
- Other government
- Collaborators
- Ministero della Salute, Italy
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05300672
- Sponsor's protocol ID
- 1123-2020-FARM-AUSLBO
- Other IDs
- 2020-005242-41
- Acronym
- FibER
- Status last verified
- Jul 2025
- First submitted
- 1 Mar 2022
- Last updated
- 1 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27289487Lansberg 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.
PubMed 17519538Trouillas 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.
PubMed 16397182Francis 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.
PubMed 1309052Tanne 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.
PubMed 11940547Vandelli 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.
PubMed 25497721Matosevic 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.
PubMed 23486872Sun 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.
PubMed 25783009Yaghi 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.
PubMed 26501741Yaghi 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.
PubMed 29097489Weiss 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.
PubMed 22024795Fenger-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.
PubMed 18818192Fassl 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.
PubMed 25324348Wikkelso 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.
PubMed 23986527Vandelli 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.
PubMed 30507073
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fibrinogen Replacement to Prevent Intracranial Haemorrhage in Ischemic Stroke Patients After Thrombolysis: a Pilot Probe Randomized Controlled Trial (FibER)
- ClinicalTrials.gov ID
- NCT05300672
- Acronym / sponsor ID
- FibER / 1123-2020-FARM-AUSLBO
- Conditions
- Intracranial Hemorrhages, Ischemic Stroke
- Keywords
- Intracranial Hemorrhages, Ischemic Stroke, Fibrinogen replacement, Thrombolysis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 207 participants (actual)
- Lead sponsor
- Azienda Usl di BolognaOther government
- Collaborators
- Ministero della Salute, Italy
- Study start
- 8 Feb 2022 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 27 May 2025 (actual)
- First posted
- 29 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fibrinogen replacement could prevent haemorrhagic complications in ischemic stroke patients with secondary post-rtPA hypofibrinogenemia
Detailed description
Intravenous recombinant tissue plasminogen activator (rtPA) is the first recommended reperfusion therapy for acute ischemic stroke, as well as endovascular treatment in case of large vessel occlusion, but it increases the risk of ICH.
The pathophysiological mechanisms of ICH after i.v. thrombolysis in ischemic stroke is complex: hyperglycemia, early ischemic changes on neuroimaging, clinical stroke severity assessed by the National Institutes of Health Stroke Scale score (NIHSS) on admission, advanced age and high blood pressure are known risk factors for hemorrhagic cerebral transformations. The risk of bleeding is likely mediated by coagulopathy, reperfusion injury, and breakdown of blood-brain barrier.
The rtPA binds the plasminogen within the clot, converting it to plasmin, a proteolytic enzyme capable to dissolve the clot. However plasmin activity is not specific for clot-associated fibrin, but also breaks down other circulating proteins, including fibrinogen. An early fibrinogen degradation coagulopathy can occur after i.v. thrombolysis, that could be implicated in bleeding complications.
In 2002, it was shown how high levels of fibrin and fibrinogen degradation factors at 2 hours after rtPA could be a risk factor for early ICH.
Few years ago, the investigators published a work demonstrating that an early decrease in fibrinogen levels is a risk factor for ICH within the first 24 hours and 7 days after rtPA therapy in ischemic stroke patients. In this experience, the investigators collected data about ischemic stroke patients that experienced a severe hypofibrinogenemia after 2 hours from iv rtPA. All patient were treated with fibrinogen replacement, fibrinogen infusion was well tolerated, without any thrombotic complication, and the infusion of fibrinogen did not reduce the rate of recanalization and, therefore, did not negatively affect the chances of reopening the occluded vessel. These data agree with another study showing that prominent fibrinogen turnover after thrombolysis is a relevant cause of major bleeding complications, and specifically that a decrease >200 mg/dL in the fibrinogen level 6 hours after thrombolysis emerges as a significant and independent predictor for bleeding risk. Morover, other authors confirmed that the decrease of fibrinogen level less than 2 g/L in the first 2 hours after thrombolysis multiplies the odds of early parenchymal hematoma (PH) by a factor of 12.82 . Similarly, a large study about symptomatic intracerebral haemorrhage (sICH) showed that severe hypofibrinogenemia (<150 mg/dL) was associated with ICH expansion.
The correction of the coagulopathy after rtPA remained the mainstay of treatment for sICH after
thrombolysis, but no specific agent has been shown to be most effective. Data from other disease states, however, raise the possibility that certain agents not routinely used, may be effective. As regard, in the consensus statement of 2017, American Heart Association Stroke (AHA) Council investigated possible treatments for sICH after rtPA in ischemic stroke patients, evaluating the role of cryoprecipitate, prothrombin complex concentrate, fresh frozen plasma, antifibrinolytic agents, platelets, Factor VI and vit. K. In particular, infusion of cryoprecipitate was suggested because it contains fibrinogen, that corrects dysfibrinogenemia. In particular, if sICH is diagnosed, physicians were recommended to consider immediately sending a blood sample for fibrinogen level and empirically transfusing with 10 U cryoprecipitate and anticipate giving more cryoprecipitate as needed to achieve a fibrinogen level of >150 mg/dL.
Indeed, several studies in other different medical fields, suggested fibrinogen supplementation with anti- haemorrhagic purposes in patients with severe haemorrhages and related fibrinogen deficiency, following trauma and surgery.
The investigators had previously analysed the trend of fibrinogen decrease after i.v. rtPA in 56 ischemic patients taking fibrinogen dosage at 2, 6, 12 and 24 hours from rtPA infusion: fibrinogen level drops within the first 2 hours and then slowly increases in the following 24 hours, still being lower than basal fibrinogen value. Dividing patients in two subgroups according to pre-rtPA fibrinogen level, a higher baseline fibrinogen resulted in higher risk of deep decrease in fibrinogen value. Medical literature about the rate of thrombotic complication after fibrinogen concentrate administration in stroke patients is relatively lacking. However, experiences in cardiac surgery showed that administration of fibrinogen concentrate was not associated with an increased risk of mortality and thromboembolic events, and a recent Cochrane review on fibrinogen concentrate in bleeding patients, did not show any adverse events such as thrombotic episodes following the use of fibrinogen concentrate.
In a pilot experience, the investigators administrated i.v. fibrinogen in 39 patients with severe hypofibrinogenemia after 2 hours from i.v. rtPA. Fibrinogen infusion was well tolerated: no thrombotic complications occurred in 37 out of 39 patients (94.77%). Two patients developed pulmonary embolism, of which 1 was only segmental and 1 in an active cancer patient. Moreover fibrinogen replacement did not reduce the rate of recanalization, so it did not negatively affect the chances of reopening the occluded vessel.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| fibrinogen infusion | Experimental | Drug: fibrinogen infusionfibrinogen infusion (2 g) in stroke patients with secondary post-rtPA hypofibrinogenemia |
| No fibrinogen infusion | No intervention | –No fibrinogen infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- contraindication to rtPA treatment;
- patients who present symptomatic ICH during infusion of rt-PA,
- absence of written informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fibrinogen infusionfibrinogen infusion (2 g) in stroke patients with secondary post-rtPA hypofibrinogenemia | Drug | fibrinogen infusion |
Primary outcome
Intracranial hemorrhage defined as parenchymal hematoma
Time frame: 7 days after randomization
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).
2 secondary outcomes
Symptomatic intracranial hemorrhage
Time frame: 7 days after randomization
Extracranial bleedings
Time frame: 7 days after randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2025.
- Background: PubMed 27289487Whiteley 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: PubMed 17519538Lansberg 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: PubMed 16397182Trouillas 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: PubMed 1309052Francis 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: PubMed 11940547Tanne 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: PubMed 25497721Vandelli 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: PubMed 23486872Matosevic 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: PubMed 25783009Sun 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: PubMed 26501741Yaghi 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: PubMed 29097489Yaghi 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: PubMed 22024795Weiss 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: PubMed 18818192Fenger-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.
- Individual participant dataSharing planned: No
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Effect of Different Intravenous Fluids on Post-operative Chronic Subdural Hematoma Size and Recurrence
Chronic Subdural Hematoma
Recruiting
Middle Meningeal Artery Embolisation in Chronic Subdural Hematoma
Chronic Subdural Hematoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing fibrinogen infusion in people with Intracranial Hemorrhages and Ischemic Stroke, run by Azienda Usl di Bologna at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intracranial hemorrhage defined as parenchymal hematoma (time frame: 7 days after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05300672, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2025.