Evaluataion of NOAC Levels in Acute Stroke

Evaluation of Non-Vitamin K Antagonist Oral Anticoagulants Concentration Among Patients With Acute Stroke (The Direct Oral AntiCoagulant Registry in Taiwan-Emergent Department, DOACT-ED)

Non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over warfarin in preventing stroke and thromboembolism among patients with atrial fibrillation (AF) in several guidelines. To evaluate the pharmacological effects of NOACs, directly measuring the concentration is the most arbitrary way since the correlation between concentration and common coagulation tests are not reliable. Our previous investigation reported under the fixed dose regimen, dabigatran exposure increased in elderly, renal impairments and patients with multiple co-morbid conditions. Our data also showed difference in NOACs exposure in Asians. For example, patients under rivaroxaban, in comparison to apxiaban, were more likely to have lower than expected range drug level. Furthermore, the NOACs concentration also affected by the prescription pattern of physicians (non-compliant to labeled dose) and patients' behavior (poor medication adherence).

The relationship between NOACs exposure and safety has been elucidated in large-scale clinical trials. As the NOACs level increased, the risk for bleeding increased, too. Nevertheless, no additional protection was noted with increased NOACs levels. In post marketing surveillance, bleeding and thrombotic events have been reported. Investigating the NOACs level among these patients helps evaluating the residual drug in the body, which could be a reference for clinical decision in emergent situation.

Specific purpose: Investigate the correlation between NOACs concentration upon the arrival of emergency department (ED) and important clinical outcomes including systemic thromboembolism, and major bleeding.

Direction for investigation:

1. Prospectively record the NOACs concentration among AF patients under NOACs therapy and suffered from ischemic stroke (IS), transient ischemic attack (TIA), intracerebral hemorrhage (ICH) and other major bleeding.
2. Investigate the correlation between NOACs concentration upon ED arrival and thromboembolic or bleeding events.
3. Propose a therapeutic range for NOACs, in order to provide a guide for important decision in acute setting.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; Anticoagulant Adverse Reaction
• Intervention / Treatment: Drug: Dabigatran, rivaroxaban, apixaban, edoxaban

Detailed Description

Non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over warfarin in preventing stroke and thromboembolism among patients with atrial fibrillation (AF) in several guidelines. To evaluate the pharmacological effects of NOACs, directly measuring the concentration is the most arbitrary way since the correlation between concentration and common coagulation tests are not reliable. Our previous investigation reported under the fixed dose regimen, dabigatran exposure increased in elderly, renal impairments and patients with multiple co-morbid conditions. Our data also showed difference in NOACs exposure in Asians. For example, patients under rivaroxaban, in comparison to apxiaban, were more likely to have lower than expected range drug level. Furthermore, the NOACs concentration also affected by the prescription pattern of physicians (non-compliant to labeled dose) and patients' behavior (poor medication adherence).

The relationship between NOACs exposure and safety has been elucidated in large-scale clinical trials. As the NOACs level increased, the risk for bleeding increased, too. Nevertheless, no additional protection was noted with increased NOACs levels. In post marketing surveillance, bleeding and thrombotic events have been reported. Investigating the NOACs level among these patients helps evaluating the residual drug in the body, which could be a reference for clinical decision in emergent situation.

Specific purpose:

1. Prospectively record the NOACs concentration among AF patients under NOACs therapy and suffered from IS, TIA, ICH or major bleeding.

   AF patients who presented to emergent department (ED) for acute IS, TIA, ICH (non-traumatic), or other major bleeding and was under NOACs therapy will be recruited to this study. Blood sample will be collected before acute management to measure NOACs concentration. Co-morbid disease, laboratory tests and concurrent medications will be retrieved from electronic medical records. The onset, location, severity of IS. ICH or other major bleeding, and the outcome and long-term managements will be prospectively recorded.

2. Investigate the correlation between NOACs concentration and thromboembolic or bleeding events.

   For each NOACs, we are going to compare the differences in NOACs exposure between patients with thromboembolism or major bleedi. Important baseline characteristics, co-medications and disease severity will be adjusted before making comparison.

3. Propose a therapeutic range for NOACs, in order to provide a guide for important decision in acute setting.

From the data of NOACs concentration among patients with IS or ICH, we plan to propose a therapeutic range with acceptable efficacy and safety for NOACs therapy. Our data will provide a guide for physicians to make important clinical decision.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Shin Yi Lin, M.S.; Phone Number: 63699 +88623123456; Email: hsin924@ntuh.gov.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Shin Yi Lin, MS; Phone Number: +886972651956; Email: hsin924@ntuh.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patient under direct oral anticoagulant therapy and suffered from ischemic stroke or intracranial hemorrhage.

Description

Inclusion Criteria:

1. Age ≥ 20 years
2. Having AF diagnosis
3. Under NOACs therapy including dabigatran, rivaroxaban, apixaban and edoxaban.
4. Admitted for acute IS, transient ischemic attack (TIA), ICH or major bleeding

Exclusion Criteria:

1. The ICH is resulted from trauma.
2. Decline the inform consent.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional outcome	Functional status measured by using the modified Rankin Scale.	3 months after stroke (ischemic or hemorrhagic)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic intracranial hemorrhage (sICH)	Type 2 parenchymal hemorrhage on the follow-up neuroimage in 24 to 36 hours after EVT, with neurological deterioration of ≥4 points on the National Institute of Health Stroke Scale (NIHSS) score from baseline	24-36 hours after stroke
Early neurological improvement	Reduction of 8 points or more in the NIHSS score within 24 hours.	24 hours after stroke
Successful reperfusion (in ischemic stroke patients receiving endovascular thrombectomy)	Defined as Thrombolysis in Cerebral Infarction (TICI) scale 2b to 3	Evaluated after EVT
Recurrent ischemic stroke	Neurological symptoms with ischemic lesion noted on neuroimaging	3 years
Recurrent intracranial hemorrhage	Neurological symptoms with hemorrhagic lesion noted on neuroimaging	3 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Shin Yi Lin, M.S., National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 17, 2023
• First Submitted That Met QC Criteria: November 17, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 22, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Ischemic stroke; Drug level; Intracranial hemorrhage; Direct oral anticoagulant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Rivaroxaban; Dabigatran; Apixaban; Edoxaban; Anticoagulants
• Other Study ID Numbers: 202003059RINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No