Trial of Andexanet Alfa in ICrH Patients Receiving an Oral FXa Inhibitor

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

Timeline

Start

2019-06-06

Primary completion

2023-05-27

Completion

2023-08-09

Outcome

Met primary endpoint

paper Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet PMID 38749032 ↗

paper (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P = 0.003). PMID 38749032 ↗

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.
• Eikelboom 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.
• Shoamanesh 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.
• Connolly 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.
• Siepen 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.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Andexanet alfa	Protein / enzyme biologic	—	—

Indications