Acute Intracranial HemorrhagePhase 4NCT03661528
Trial of Andexanet Alfa in ICrH Patients Receiving an Oral FXa Inhibitor
A Phase 4 study testing andexanet alfa in people with Acute Intracranial Hemorrhage, run by Alexion Pharmaceuticals, Inc. at 142 sites in 24 countries.
Trial summary
Randomized, controlled clinical trial evaluating the efficacy and safety of andexanet alfa versus usual care in patients with intracranial hemorrhage anticoagulated with a direct oral FXa anticoagulant Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Intracranial Hemorrhage
- What is being tested?
- andexanet alfa
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 530 participants
- Where
- 142 sitesin 24 countries
- Study dates
- 6 Jun 2019to 9 Aug 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Written informed consent. Either the patient or his or her medical proxy (or legally authorized representative if permissible by local or regional laws and regulations) has been adequately informed of the nature and risks of the study and has given written informed consent prior to Screening.
- Deferred consent procedure is allowed where approved by local ethics committees. In cases of deferred consent, the time of the study physician's documented decision to include the patient into the study will serve as "time of consent" with respect to protocol-specific procedures.
- In all cases where the patient does not sign informed consent prior to study entry, informed consent from the patient will be obtained as soon as realistically possible after inclusion in the trial and in accordance with the Declaration of Helsinki, International Conference on Harmonization-Good Clinical Practice (GCP), the EU General Data Protection Regulation (GDPR) and national and local regulations.
- Age ≥ 18 years old at the time of consent.
- An acute intracerebral bleeding episode, defined as an estimated blood volume ≥ 0.5 to ≤ 60 mL acutely observed radiographically within the cerebrum. Patients may have extracerebral (e.g., subdural, subarachnoid, epidural) or extracranial (e.g., gastrointestinal, intraspinal) bleeding additionally, but the intracerebral hemorrhage must be considered the most clinically significant bleed at the time of enrollment.
- Performance of a head CT or MRI scan demonstrating the intracerebral bleeding within 2 hours prior to randomization (the baseline scan may be repeated only once to meet this criterion).
Show all 13Show fewer
- Treatment with an oral FXa inhibitor (apixaban [last dose 2.5 mg or greater], rivaroxaban [last dose 10 mg or greater], or edoxaban [last dose 30 mg or greater]):
- ≤ 15 hours prior to randomization.
- > 15 hours prior to randomization or unknown time of last dose, if documented anti fXa activity is > 100 ng/mL for direct fXa inhibitors (apixaban, rivaroxaban or edoxaban) may be enrolled, irrespective of the time of the last dose, and the local anti-fXa activity level is obtained within 2 hours prior to consent, performed as per standard of care. Note: Patients enrolled in this manner should receive a high andexanet dosing regimen.
- Time from bleeding symptom onset < 6 hours prior to the baseline imaging scan. Time of trauma (if applicable) or time last seen normal may be used as surrogates for time of symptom onset. (If the baseline scan is repeated to meet Inclusion Criterion #4, the time from bleeding symptom onset must be < 6 hours prior to the repeat baseline imaging scan.)
- Female patients of childbearing potential and male patients with female partners of childbearing potential must follow protocol-specified guidance for avoiding pregnancy for 30 days after the last dose of study drug.
- Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
- NIHSS score ≤ 35 at the time of consent.
Who cannot join
- If a patient meets any of the following criteria, he or she is not eligible to participate in this trial:
- Planned surgery, including Burr holes for hematoma drainage, within 12 hours after randomization. Minimally invasive surgery/procedures not directly related to the treatment of intracranial bleeding and that are not expected to significantly affect hematoma volume are allowed (e.g., Burr holes for intracranial pressure monitoring, endoscopy, bronchoscopy, central lines.
- GCS score < 7 at the time of consent. If a patient is intubated and/or sedated at the time of consent, they may be enrolled if it can be documented that they were intubated/sedated for non-neurologic reasons within 2 hours prior to consent.
- Purposefully left blank.
- Anticipation that the baseline and follow up brain scans will not be able to use the same imaging modalities (i.e., patients with a baseline CT scan should have a CT scan in follow up; similarly, for MRI).
- Expected survival of less than 1 month (not related to the intracranial bleed).
Show all 19Show fewer
- Recent history (within 2 weeks) of a diagnosed TE or clinically relevant symptoms of the following:
- ○ Venous Thromboembolism (VTE: e.g., deep venous thrombosis, PE, cerebral venous thrombosis), myocardial infarction (MI), Disseminated Intravascular Coagulation (DIC), cerebral vascular accident, transient ischemic attack (TIA), acute coronary syndrome, or arterial systemic embolism.
- Acute decompensated heart failure or cardiogenic shock at the time of randomization.
- Severe sepsis or septic shock at the time of randomization.
- The patient is a pregnant or lactating female.
- Receipt of any of the following drugs or blood products within 7 days prior to consent:
- VKA (e.g., warfarin).
- Dabigatran.
- PCC (e.g., KCentra®) or rfVIIa (e.g., NovoSeven®), or anti-inhibitor coagulant complex (e.g., FEIBA®), FFP, and whole blood.
- Past use of andexanet (or planned use of commercial andexanet).
- Treatment with an investigational drug < 30 days prior to consent.
- Any tumor-related bleeding.
- Known hypersensitivity to any component of andexanet.
Trial locations and contacts
142 sites in 24 countries.
142 sites in 24 countries
Germany31 sites
Research Site
Altenburg, 4600
Research Site
Augsburg, 86156
Research Site
Bad Neustadt an der Saale, 97616
Research Site
Bochum, 44892
Research Site
Bonn, 53127
Research Site
Bremen, 28755
Research Site
Chemnitz, 9116
Research Site
Dortmund, 44137
Research Site
Dresden, 1067
Research Site
Dresden, 1307
Research Site
Erlangen, 91054
Research Site
Essen, 45131
Research Site
Frankfurt, 65929
Research Site
Frankfurt am Main, 60528
Research Site
Giessen, 35392
Research Site
Göttingen, 37075
Research Site
Hamburg, 20246
Research Site
Hamburg, 22291
Research Site
Hanover, 30625
Research Site
Heidelberg, 69120
Research Site
Konstanz, 78464
Research Site
Lübeck, 23538
Research Site
Lünen, 44534
Research Site
Mannheim, 68135
Research Site
München, 81377
Research Site
Münster, 48149
Research Site
Osnabrück, 49076
Research Site
Sande, 26452
Research Site
Stuttgart, 70174
Research Site
Tübingen, 72076
Research Site
Ulm, 89081
United States11 sites
Research Site
Albany, New York, 12208
Research Site
Allentown, Pennsylvania, 18103
Research Site
Augusta, Georgia, 30905
Research Site
Austin, Texas, 78705
Research Site
Austin, Texas, 78712
Research Site
Columbus, Ohio, 43210
Research Site
Fort Lauderdale, Florida, 33308
Research Site
Nashville, Tennessee, 37203
Research Site
Royal Oak, Michigan, 48073
Research Site
Troy, Michigan, 48085
Research Site
Tulsa, Oklahoma, 74104
France11 sites
Research Site
Angers, 49933
Research Site
Bordeaux, 33076
Research Site
Bourg-en-Bresse, 01012
Research Site
Clermont-Ferrand, 63003
Research Site
Lyon, 69437
Research Site
Montpellier, 34295
Research Site
Nancy, 54035
Research Site
Paris, 75014
Research Site
Paris, 75019
Research Site
Suresnes, 92151
Research Site
Toulouse, 31300
Spain10 sites
Research Site
Albacete, 02006
Research Site
Barcelona, 08035
Research Site
Barcelona, 08041
Research Site
L'Hospitalet de Llobregat, 08907
Research Site
Lleida, 25198
Research Site
Madrid, 28034
Research Site
Madrid, 28041
Research Site
Seville, 41009
Research Site
Seville, 41013
Research Site
Valencia, 46026
Canada9 sites
Research Site
Calgary, Alberta, T2N 2T9
Research Site
Edmonton, Alberta, T6G 2B7
Research Site
Hamilton, Ontario, L8L 2X2
Research Site
London, Ontario, N6A 5A5
Research Site
Montreal, Quebec, H3A 2B4
Research Site
Montreal, Quebec, H3T 1E2
Research Site
New Westminster, British Columbia, V3L 0E3
Research Site
Québec, Quebec, G1J 4Z1
Research Site
Vancouver, British Columbia, V5Z 1M9
Italy8 sites
Research Site
Bologna, 40133
Research Site
Genova, 16132
Research Site
Milan, 20132
Research Site
Perugia, 06156
Research Site
Roma, 00133
Research Site
Roma, 00168
Research Site
Rome, 152
Research Site
Rome, 161
Israel7 sites
Research Site
Ashdod, 7747629
Research Site
Beersheba, 84101
Research Site
Haifa, 3109601
Research Site
Jerusalem, 91120
Research Site
Jerusalem, 9372212
Research Site
Petah Tikva, 4941492
Research Site
Tel Aviv, 6423906
Austria6 sites
Research Site
Innsbruck, 6020
Research Site
Klagenfurt, 9020
Research Site
Linz, 4020
Research Site
Salzburg, 5020
Research Site
Sankt Pölten, 3100
Research Site
Vienna, 1020
Belgium6 sites
Research Site
Belgium, 1200
Research Site
Genk, 3600
Research Site
Ghent, 9000
Research Site
Kortrijk, 8500
Research Site
Leuven, 3000
Research Site
Ottignies, 1340
United Kingdom6 sites
Research Site
Cambridge, CB2 0QQ
Research Site
Harrow, HA1 3UJ
Research Site
Leeds, LS1 3EX
Research Site
Leicester, LE1 5WW
Research Site
London, SW17 0QT
Research Site
Newcastle upon Tyne, NE1 4LP
Denmark5 sites
Research Site
Aalborg, 9100
Research Site
Århus N, 8200
Research Site
Copenhagen, DK-2400
Research Site
Copenhagen Ø, 2100
Research Site
Odense C, 5000
Hungary5 sites
Research Site
Budapest, 1083
Research Site
Budapest, 1106
Research Site
Budapest, 1134
Research Site
Debrecen, 4032
Research Site
Pécs, 7623
Netherlands5 sites
Research Site
Amsterdam, 1061 AE
Research Site
Amsterdam, 1105 AZ
Research Site
Enschede, 7512 KZ
Research Site
Leiden, 2333 ZA
Research Site
Zwolle, 8025 AB
Poland4 sites
Research Site
Krakow, 30-688
Research Site
Krakow, 31-913
Research Site
Lublin, 20-718
Research Site
Wejherowo, 84-200
Czechia3 sites
Research Site
Brno, 656 91
Research Site
Ostrava, 703 84
Research Site
Prague, 150 06
Portugal2 sites
Research Site
Coimbra, 3000-075
Research Site
Vila Nova de Gaia, 4434-502
Russia2 sites
Research Site
Arkhangelsk, 163045
Research Site
Novosibirsk, 630003
About this study
Official title: A Randomized Clinical Trial of Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor
Randomized, controlled clinical trial evaluating the efficacy and safety of andexanet alfa versus usual care in patients with intracranial hemorrhage anticoagulated with a direct oral FXa anticoagulant
Read the detailed description
This is a randomized, multicenter clinical trial designed to determine the efficacy and safety of andexanet alfa compared to usual care in patients presenting with acute intracranial hemorrhage within 6 hours of symptom onset to baseline scan and within 15 hours of taking an oral factor Xa inhibitor. The study will use a prospective, randomized, open label (PROBE) design. The primary efficacy outcome will be adjudicated by a blinded Endpoint Adjudication Committee. To support the adjudication of hemostatic efficacy, a blinded Imaging Core Laboratory will review all available scans. Between 900 and 1200 patients are planned to be enrolled in the study.
- Conditions
- Acute Intracranial Hemorrhage
- Being tested
- andexanet alfa, Usual Care
- Keywords
- thrombosis, anticoagulant, acute intracranial hemorrhage, andexanet alfa
- Medical subject headings
- Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
andexanet alfaDrug
Andexanet alfa is a recombinant version of human FXa
Usual CareDrug
Usual care will consist of any treatment(s) (including no treatment) other than andexanet alfa administered within 3 hours post-randomization that the Investigator and/or other treating physicians consider to be appropriate.
| Study group | Role | What they receive |
|---|---|---|
| andexanet alfa | Experimental | Patients will receive one of two dosing regimens of andexanet alfa based on which FXa inhibitor they received and the amount and timing of the most recent dose. Receives: Drug: andexanet alfa |
| Usual Care | Other | Usual care will consist of any treatment(s) (including no treatment) other than andexanet alfa administered within 3 hours post-randomization that the Investigator and/or other treating physicians consider to be appropriate. Receives: Drug: Usual Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Achieved Effective Hemostasis
Effective hemostasis was defined as a change from baseline in National Institutes of Health Stroke Scale (NIHSS) of + 6 or less at the 12 hour timepoint and ≤35% increase in haematoma volume compared to baseline on a repeat computed tomography (CT) or magnetic resonance imaging (MRI) scan at 12 hours and no rescue therapies administered between 3 hours and 12 hours after randomization (defined as excellent or good hemostasis). The NIHSS is a validated quantitative assessment tool to measure stroke-related neurological deficits and ranges from 0 (no neurological deficits) to a maximum of 42, indicative of a very severe level of impairment. Data presented is for the number of participants who achieved effective hemostasis (excellent or good hemostasis), as adjudicated by the independent Endpoint Adjudication Committee (IEAC).
Measured: Baseline up to 12 hours
Secondary outcomes (1)
Percentage Change From Baseline to Nadir in Anti-FXa Activity
Anti-FXa activity was measured from plasma samples to assess the anticoagulant status of FXa inhibitors using a modified chromogenic assay performed at a Central Laboratory. Nadir was defined as the minimum anti-FXa activity post-randomization.
Measured: Baseline up to 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2018
- Study start6 Jun 2019
- Primary completion27 May 2023
- Study completion9 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Acute Intracranial HemorrhageStudies of the same condition, open and under way.
- More trials run by Alexion Pharmaceuticals, Inc.The sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 530 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexion Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03661528
- Sponsor's protocol ID
- 18-513
- Other IDs
- 2018-002620-17, 2018
- Status last verified
- Jul 2024
- First submitted
- 30 Aug 2018
- Last updated
- 3 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Shoamanesh A, Connolly SJ, Demchuk AM, Seiffge DJ, Sandset EC, Molina CA, Tsivgoulis G, Christensen H, Beyer-Westendorf J, Coutinho JM, Amarenco P, Lemmens R, Veltkamp R, Middeldorp S, Zini A, Himmelmann A, Ladenvall P, Knutsson M, Xu L, Crowther M, Sharma M; ANNEXA-I Investigators. Predictors of Hematoma Expansion and Response to Andexanet in Patients With Intracerebral Hemorrhage: Secondary Analyses of the ANNEXA-I Randomized Clinical Trial. Stroke. 2026 Jul;57(7):1920-1928. doi: 10.1161/STROKEAHA.124.050418. Epub 2026 May 7.
PubMed 42093656Eikelboom JW, Sharma M, Xu L, Bamberg K, Beyer-Westendorf J, Falkenberg C, Ladenvall P, Narayan R, Penland RC, Verhamme P, Shoamanesh A. Association of Biomarkers With Intracerebral Hematoma Expansion and Arterial Thromboembolic Events in Patients With Acute Intracranial Hemorrhage: The ANNEXA-I Biomarker Substudy. Stroke. 2025 Jul;56(7):1807-1815. doi: 10.1161/STROKEAHA.124.049966. Epub 2025 Apr 28.
PubMed 40289797Shoamanesh A, Sharma M. Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage. Reply. N Engl J Med. 2024 Aug 22;391(8):10.1056/NEJMc2407378#sa4. doi: 10.1056/NEJMc2407378. No abstract available.
PubMed 39167819Connolly SJ, Sharma M, Cohen AT, Demchuk AM, Czlonkowska A, Lindgren AG, Molina CA, Bereczki D, Toni D, Seiffge DJ, Tanne D, Sandset EC, Tsivgoulis G, Christensen H, Beyer-Westendorf J, Coutinho JM, Crowther M, Verhamme P, Amarenco P, Roine RO, Mikulik R, Lemmens R, Veltkamp R, Middeldorp S, Robinson TG, Milling TJ Jr, Tedim-Cruz V, Lang W, Himmelmann A, Ladenvall P, Knutsson M, Ekholm E, Law A, Taylor A, Karyakina T, Xu L, Tsiplova K, Poli S, Kallmunzer B, Gumbinger C, Shoamanesh A; ANNEXA-I Investigators. Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage. N Engl J Med. 2024 May 16;390(19):1745-1755. doi: 10.1056/NEJMoa2313040.
PubMed 38749032Siepen BM, Polymeris A, Shoamanesh A, Connolly S, Steiner T, Poli S, Lemmens R, Goeldlin MB, Muller M, Branca M, Rauch J, Meinel T, Kaesmacher J, Z'Graggen W, Arnold M, Fischer U, Peters N, Engelter ST, Lyrer P, Seiffge D. Andexanet alfa versus non-specific treatments for intracerebral hemorrhage in patients taking factor Xa inhibitors - Individual patient data analysis of ANNEXA-4 and TICH-NOAC. Int J Stroke. 2024 Jun;19(5):506-514. doi: 10.1177/17474930241230209. Epub 2024 Mar 8.
PubMed 38264861
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Clinical Trial of Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor
- ClinicalTrials.gov ID
- NCT03661528
- Acronym / sponsor ID
- 18-513
- Conditions
- Acute Intracranial Hemorrhage
- Keywords
- thrombosis, anticoagulant, acute intracranial hemorrhage, andexanet alfa
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 530 participants (actual)
- Lead sponsor
- Alexion Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 6 Jun 2019 (actual)
- Primary completion
- 27 May 2023 (actual)
- Study completion
- 9 Aug 2023 (actual)
- First posted
- 7 Sep 2018 (actual)
- Results
- Posted 3 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomized, controlled clinical trial evaluating the efficacy and safety of andexanet alfa versus usual care in patients with intracranial hemorrhage anticoagulated with a direct oral FXa anticoagulant
Detailed description
This is a randomized, multicenter clinical trial designed to determine the efficacy and safety of andexanet alfa compared to usual care in patients presenting with acute intracranial hemorrhage within 6 hours of symptom onset to baseline scan and within 15 hours of taking an oral factor Xa inhibitor. The study will use a prospective, randomized, open label (PROBE) design. The primary efficacy outcome will be adjudicated by a blinded Endpoint Adjudication Committee. To support the adjudication of hemostatic efficacy, a blinded Imaging Core Laboratory will review all available scans. Between 900 and 1200 patients are planned to be enrolled in the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| andexanet alfa | Experimental | Drug: andexanet alfaPatients will receive one of two dosing regimens of andexanet alfa based on which FXa inhibitor they received and the amount and timing of the most recent dose. |
| Usual Care | Other | Drug: Usual CareUsual care will consist of any treatment(s) (including no treatment) other than andexanet alfa administered within 3 hours post-randomization that the Investigator and/or other treating physicians consider to be appropriate. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Written informed consent. Either the patient or his or her medical proxy (or legally authorized representative if permissible by local or regional laws and regulations) has been adequately informed of the nature and risks of the study and has given written informed consent prior to Screening.
- Age ≥ 18 years old at the time of consent.
- An acute intracerebral bleeding episode, defined as an estimated blood volume ≥ 0.5 to ≤ 60 mL acutely observed radiographically within the cerebrum. Patients may have extracerebral (e.g., subdural, subarachnoid, epidural) or extracranial (e.g., gastrointestinal, intraspinal) bleeding additionally, but the intracerebral hemorrhage must be considered the most clinically significant bleed at the time of enrollment.
- Performance of a head CT or MRI scan demonstrating the intracerebral bleeding within 2 hours prior to randomization (the baseline scan may be repeated only once to meet this criterion).
- Treatment with an oral FXa inhibitor (apixaban [last dose 2.5 mg or greater], rivaroxaban [last dose 10 mg or greater], or edoxaban [last dose 30 mg or greater]):
Key exclusion criteria (19 listed)
- If a patient meets any of the following criteria, he or she is not eligible to participate in this trial:
- Planned surgery, including Burr holes for hematoma drainage, within 12 hours after randomization. Minimally invasive surgery/procedures not directly related to the treatment of intracranial bleeding and that are not expected to significantly affect hematoma volume are allowed (e.g., Burr holes for intracranial pressure monitoring, endoscopy, bronchoscopy, central lines.
- GCS score < 7 at the time of consent. If a patient is intubated and/or sedated at the time of consent, they may be enrolled if it can be documented that they were intubated/sedated for non-neurologic reasons within 2 hours prior to consent.
- Purposefully left blank.
- Anticipation that the baseline and follow up brain scans will not be able to use the same imaging modalities (i.e., patients with a baseline CT scan should have a CT scan in follow up; similarly, for MRI).
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 |
|---|---|---|
| andexanet alfaAndexanet alfa is a recombinant version of human FXa | Drug | andexanet alfa |
| Usual CareUsual care will consist of any treatment(s) (including no treatment) other than andexanet alfa administered within 3 hours post-randomization that the Investigator and/or other treating physicians consider to be appropriate. | Drug | Usual Care |
Primary outcome
Number of Participants Who Achieved Effective Hemostasis
Time frame: Baseline up to 12 hours
Effective hemostasis was defined as a change from baseline in National Institutes of Health Stroke Scale (NIHSS) of + 6 or less at the 12 hour timepoint and ≤35% increase in haematoma volume compared to baseline on a repeat computed tomography (CT) or magnetic resonance imaging (MRI) scan at 12 hours and no rescue therapies administered between 3 hours and 12 hours after randomization (defined as excellent or good hemostasis). The NIHSS is a validated quantitative assessment tool to measure stroke-related neurological deficits and ranges from 0 (no neurological deficits) to a maximum of 42, indicative of a very severe level of impairment. Data presented is for the number of participants who achieved effective hemostasis (excellent or good hemostasis), as adjudicated by the independent Endpoint Adjudication Committee (IEAC).
1 secondary outcome
Percentage Change From Baseline to Nadir in Anti-FXa Activity
Time frame: Baseline up to 2 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42093656Shoamanesh A, Connolly SJ, Demchuk AM, Seiffge DJ, Sandset EC, Molina CA, Tsivgoulis G, Christensen H, Beyer-Westendorf J, Coutinho JM, Amarenco P, Lemmens R, Veltkamp R, Middeldorp S, Zini A, Himmelmann A, Ladenvall P, Knutsson M, Xu L, Crowther M, Sharma M; ANNEXA-I Investigators. Predictors of Hematoma Expansion and Response to Andexanet in Patients With Intracerebral Hemorrhage: Secondary Analyses of the ANNEXA-I Randomized Clinical Trial. Stroke. 2026 Jul;57(7):1920-1928. doi: 10.1161/STROKEAHA.124.050418. Epub 2026 May 7.
- Derived from this study: PubMed 40289797Eikelboom JW, Sharma M, Xu L, Bamberg K, Beyer-Westendorf J, Falkenberg C, Ladenvall P, Narayan R, Penland RC, Verhamme P, Shoamanesh A. Association of Biomarkers With Intracerebral Hematoma Expansion and Arterial Thromboembolic Events in Patients With Acute Intracranial Hemorrhage: The ANNEXA-I Biomarker Substudy. Stroke. 2025 Jul;56(7):1807-1815. doi: 10.1161/STROKEAHA.124.049966. Epub 2025 Apr 28.
- Derived from this study: PubMed 39167819Shoamanesh A, Sharma M. Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage. Reply. N Engl J Med. 2024 Aug 22;391(8):10.1056/NEJMc2407378#sa4. doi: 10.1056/NEJMc2407378. No abstract available.
- Derived from this study: PubMed 38749032Connolly SJ, Sharma M, Cohen AT, Demchuk AM, Czlonkowska A, Lindgren AG, Molina CA, Bereczki D, Toni D, Seiffge DJ, Tanne D, Sandset EC, Tsivgoulis G, Christensen H, Beyer-Westendorf J, Coutinho JM, Crowther M, Verhamme P, Amarenco P, Roine RO, Mikulik R, Lemmens R, Veltkamp R, Middeldorp S, Robinson TG, Milling TJ Jr, Tedim-Cruz V, Lang W, Himmelmann A, Ladenvall P, Knutsson M, Ekholm E, Law A, Taylor A, Karyakina T, Xu L, Tsiplova K, Poli S, Kallmunzer B, Gumbinger C, Shoamanesh A; ANNEXA-I Investigators. Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage. N Engl J Med. 2024 May 16;390(19):1745-1755. doi: 10.1056/NEJMoa2313040.
- Derived from this study: PubMed 38264861Siepen BM, Polymeris A, Shoamanesh A, Connolly S, Steiner T, Poli S, Lemmens R, Goeldlin MB, Muller M, Branca M, Rauch J, Meinel T, Kaesmacher J, Z'Graggen W, Arnold M, Fischer U, Peters N, Engelter ST, Lyrer P, Seiffge D. Andexanet alfa versus non-specific treatments for intracerebral hemorrhage in patients taking factor Xa inhibitors - Individual patient data analysis of ANNEXA-4 and TICH-NOAC. Int J Stroke. 2024 Jun;19(5):506-514. doi: 10.1177/17474930241230209. Epub 2024 Mar 8.
- Related InfoLink provided by the sponsor.
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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.
142 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing andexanet alfa in people with Acute Intracranial Hemorrhage, run by Alexion Pharmaceuticals, Inc. at 142 sites in 24 countries.
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 13 inclusion and 19 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 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 142 sites in Germany, United States, France, Spain, Canada and 19 more countries. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants Who Achieved Effective Hemostasis (time frame: Baseline up to 12 hours). 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 NCT03661528, which also lists 5 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 3 Jul 2024.