Anticoagulant-associated Intracranial Hemorrhage

Intracranial Hemorrhages Clinical Trial

— AAIHINNN  

Official title:

Anticoagulant-associated Intracranial Hemorrhage: Patient Characteristics and Outcomes From National Institute of Neurology and Neurosurgery Manuel Velasco: Single-Center Observational Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06168838
• Other study ID #: INNN-DI-CI-271-2023
• Status: Recruiting
• Start date: August 9, 2023
• Est. completion date: January 31, 2024

Study information

• Verified date: December 2023
• Source: El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
• Contact: Andrés Alberto Mercado Pompa, MD
• Phone: +525556063822
• Email: clinica-evc[@]innn.edu.mx
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Oral anticoagulant therapy, including factors Xa and 2a inhibitors has become more popular in recent years due to its efficacy and convenience in preventing thrombotic events and reducing the risk for stroke in patients with rosk factors (e.g. atrial fibrillation, deep venous thrombosis, pulmonary embolism). These drugs have replaced traditional therapies such as warfarin, which requires frequent dose adjustments and control blood samples. Warfarin also has a higher risk of bleeding events.

Many patients with atrial fibrillation, particularly old patients and those with comorbidities may have trouble achieving the dose and control requirements for warfarin therapy. On the other hand, Direct Oral Anticoagulant therapies do not require a close monitorization and have a lower risk of bleeding events, which makes them a more attractive option for many patients.

There is solid evidence behind the efficacy and safety of Direct Oral Anticoagulant therapies. Multiple clinical trials have demonstrated that Factor Xa inhibitors like rivaroxaban and apixaban are as effective as warfarin in preventing blood clots and reducing stroke risk in patients living with atrial fibrillation.

These challenges remark the need for new research that can improve our comprehension about the risk of bleeding associated to anticoagulant therapies and develop novel and more effective strategies for minimizing this risk.

Hence, an observational analysis about anticoagulant-associated intracranial hemorrhage may help identifying its incidence and prevalence, as well as treatment patterns and identifying any patient with risk factors linked to these events.

This information can be used to improve patient outcomes and guide future research.

Work Hypothesis: The majority of intracranial hemorrhage events are associated with heparin, low molecular weight heparin and warfarin instead of Factor Xa inhibitors or direct thrombin inhibitors. Nevertheless, the growing use in recent years of factor Xa inhibitors can increase the number of this therapy related bleeding events.

Description:

Study observational. The total number of subjects for this study will be determined by the number of patients with intracranial bleeding associated with anticoagulant therapy on the clinical records.

Primary objective: To identify the incidence and prevalence of intracranial bleeding events associated to oral anticoagulant therapy including vitamin k antagonists, factor Xa inhibitors and factor 2a inhibitors.

Secondary objective:

• To identify mortality related to intracranial bleeding associated with oral anticoagulant therapy, including vitamin K antagonists, factor Xa inhibitors and factor 2a inhibitors.

• To identify patients´ characteristics correlated with intracranial hemorrhage associated with oral anticoagulants.

• To identify treatment patterns: anticoagulant-associated intracranial bleeding management, including clinical, pharmacological, surgical, and interventional treatments, as well as procoagulant therapies.

Sample size Justification / Statistical Analysis: Non probabilistic, incidental reasoned selection.

The sample size will be determined by the number of patients with intracranial hemorrhage associated with anticoagulation in the clinical records. All electronic medical records that meet the inclusion criteria will be included in the analysis.

Descriptive analysis:

Descriptive statistics will be used for demographic and clinical characteristics of the study sample. This will include measures of central tendency (mean, median) and measures of dispersion (standard deviation, range).

Analytic (Inferential) analysis:

A univariate analysis will take place in order to examine the relationship between demographic and clinical variables with anticoagulation-associated intracranial hemorrhage This will include chi-squared tests for categorical data and T-tests or Mann-Whitney U Tests for continuous data.

A multivariable logistic regression analysis will be done to identify independent predictors of intracranial bleeding associated with anticoagulant therapy. The variables to include in the model will be determined by de univariate analysis results.

The investigators will consider a p-value under 0.05 for statistical significance.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: January 31, 2024
• Est. primary completion date: January 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Age >18 years

• Intracranial hemorrhage diagnosis and concomitant oral anticoagulant therapy

• Available clinical record from January 2015 to July 2023

Exclusion Criteria:

• Non available clinical record

• Patients that did not complete follow up on days 30 and 90 after an intracranial bleeding.

Related Conditions & MeSH terms

• Anticoagulant-induced Bleeding
• Hemorrhage
• Intracranial Hemorrhages

Intervention

Drug:
• Anticoagulant
Know the casuistry of spontaneous intracranial hemorrhages and secondary to the use of both oral and parenteral anticoagulants

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Neurología y Neurocirugía	Mexico City

Sponsors (2)

Lead Sponsor	Collaborator
El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez	AstraZeneca

Country where clinical trial is conducted

Mexico, 

References & Publications (17)

Adachi T, Hoshino H, Takagi M, Fujioka S; Saiseikai Stroke Research Group. Volume and Characteristics of Intracerebral Hemorrhage with Direct Oral Anticoagulants in Comparison with Warfarin . Cerebrovasc Dis Extra. 2017;7(1):62-71. doi: 10.1159/000462985. — View Citation

Ballestri S, Romagnoli E, Arioli D, Coluccio V, Marrazzo A, Athanasiou A, Di Girolamo M, Cappi C, Marietta M, Capitelli M. Risk and Management of Bleeding Complications with Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Venous Thromb — View Citation

Barrios V, Cinza-Sanjurjo S, Gavin O, Egocheaga I, Burgos-Pol R, Soto J, Polanco C, Suarez J, Casado MA. Cost and burden of poor anticoagulation control with vitamin K antagonists in patients with nonvalvular atrial fibrillation in Spain. Rev Esp Cardiol — View Citation

Deitelzweig S, Neuman WR, Lingohr-Smith M, Menges B, Lin J. Incremental economic burden associated with major bleeding among atrial fibrillation patients treated with factor Xa inhibitors. J Med Econ. 2017 Dec;20(12):1217-1223. doi: 10.1080/13696998.2017. — View Citation

Flaherty ML. Anticoagulant-associated intracerebral hemorrhage. Semin Neurol. 2010 Nov;30(5):565-72. doi: 10.1055/s-0030-1268866. Epub 2011 Jan 4. — View Citation

Grysiewicz R, Gorelick PB. Incidence, mortality, and risk factors for oral anticoagulant-associated intracranial hemorrhage in patients with atrial fibrillation. J Stroke Cerebrovasc Dis. 2014 Nov-Dec;23(10):2479-2488. doi: 10.1016/j.jstrokecerebrovasdis. — View Citation

Hellenbart EL, Faulkenberg KD, Finks SW. Evaluation of bleeding in patients receiving direct oral anticoagulants. Vasc Health Risk Manag. 2017 Aug 23;13:325-342. doi: 10.2147/VHRM.S121661. eCollection 2017. — View Citation

Izumi C, Miyake M, Amano M, Kitai T, Obayashi Y, Takegami M, Kimura T, Sugio K, Matsumoto T, Nishimura K, Furukawa Y. Registry of antithrombotic therapy in atrial fibrillation patients with bioprosthetic valves: A retrospective observational study. J Card — View Citation

Lip GYH, Banerjee A, Boriani G, Chiang CE, Fargo R, Freedman B, Lane DA, Ruff CT, Turakhia M, Werring D, Patel S, Moores L. Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest. 2018 Nov;154(5):1121-1201. doi: 10. — View Citation

Milling TJ Jr, Frontera J. Exploring indications for the Use of direct oral anticoagulants and the associated risks of major bleeding. Am J Manag Care. 2017 Apr;23(4 Suppl):S67-S80. — View Citation

Miyamoto S, Ikeda T, Ogawa S, Kitazono T, Nakagawara J, Minematsu K, Murakawa Y, Iwashiro S, Takeichi M, Kidani Y, Okayama Y, Sunaya T, Sato S, Yamanaka S. Clinical Risk Factors of Thromboembolic and Major Bleeding Events for Patients with Atrial Fibrilla — View Citation

Qureshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet. 2009 May 9;373(9675):1632-44. doi: 10.1016/S0140-6736(09)60371-8. — View Citation

Rohla M, Weiss TW, Pecen L, Patti G, Siller-Matula JM, Schnabel RB, Schilling R, Kotecha D, Lucerna M, Huber K, De Caterina R, Kirchhof P. Risk factors for thromboembolic and bleeding events in anticoagulated patients with atrial fibrillation: the prospec — View Citation

Roskell NS, Samuel M, Noack H, Monz BU. Major bleeding in patients with atrial fibrillation receiving vitamin K antagonists: a systematic review of randomized and observational studies. Europace. 2013 Jun;15(6):787-97. doi: 10.1093/europace/eut001. Epub 2 — View Citation

Rozjabek HM, Coleman CI, Ashton V, Laliberte F, Oyefesobi P, Lejeune D, Germain G, Schein JR, Yuan Z, Lefebvre P, Peterson ED. Healthcare costs of stroke and major bleeding in patients with atrial fibrillation treated with non-vitamin K antagonist oral an — View Citation

Ruiz-Sandoval JL, Chiquete E, Garate-Carrillo A, Ochoa-Guzman A, Arauz A, Leon-Jimenez C, Carrillo-Loza K, Murillo-Bonilla LM, Villarreal-Careaga J, Barinagarrementeria F, Cantu-Brito C; RENAMEVASC investigators. Spontaneous intracerebral hemorrhage in Me — View Citation

You JJ, Singer DE, Howard PA, Lane DA, Eckman MH, Fang MC, Hylek EM, Schulman S, Go AS, Hughes M, Spencer FA, Manning WJ, Halperin JL, Lip GYH. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: Am — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Know incidence and prevalence of intracranial bleeding events	To identify the incidence and prevalence of intracranial bleeding events associated to oral anticoagulant therapy including vitamin k antagonists, factor Xa inhibitors and factor 2a inhibitors.	From January 2015 to November 2023