Adding Antiplatelet During Edoxaban Treatment in Stroke Patients With Non-valvular Atrial Fibrillation (ADD-ON) ((ADD-ON))

October 10, 2019 updated by: Sun U. Kwon, Asan Medical Center

The Role of Additional Antiplatelet Therapy in the Ischemic Stroke With Atrial Fibrillation and Co-morbiD Atherosclerosis During edOxaban treatmeNt. (ADD-ON) Study, Multicenter Registry-based Analysis

This study aims to compare the effectiveness and safety regarding treatment with standard anticoagulant only or adding antiplatelet to anticoagulant in patients with non-valvular atrial fibrillation and significant atherosclerosis including extracranial, intracranial, coronary or peripheral artery.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Although there is a significant increase in the risk of cerebral infarction in the presence of atrial fibrillation, it is difficult to say that all cerebral infarctions occurring in patients with atrial fibrillation are caused by atrial fibrillation. Carotid stenosis is found in 1/4 of patients with atrial fibrillation, which increases the risk of cerebral infarction. Additional antiplatelet therapy to standard anticoagulation therapy should be considered in some patients. To date, the best medical treatment for prevention of cerebral infarction in patients with atrial fibrillation and accompanying atherosclerosis has not been evaluated yet.

Edoxaban reduced bleeding complication compared to warfarin in patients with atrial fibrillation. In addition, the ENGAGE AF TIMI-48 study showed a tendency to reduce cerebral infarction (p for interaction = 0.08) when administered in combination with one antiplatelet agent and edoxaban. The administration of antiplatelet agents may be due to patients had accompanying myocardial infarction or cerebral infarction. This group is also thought to have a high risk of bleeding due to high HAS-BLED scores. Nonetheless, there was a similar degree of bleeding in patients receiving additional antiplatelet agents. There was also less bleeding in the warfarin arm than in the use of additional antiplatelet agents. (Major bleeding: 0.19 vs 0.24% / yr; intracranial hemorrhage: 0.43 vs 0.57% / yr)

Thus, Edoxaban have good clinical trial results in combination with antiplatelet agents in atrial fibrillation with atherosclerosis compared to other NOACs(new oral anticoagulants). It is also considered to be suitable for combination therapy with antiplatelet agents because of its advantages in different bleeding compared to other warfarin. However, there is no evidence to suggest that Edoxaban alone or in combination with additional antiplatelet agents is better for stroke patients with atrial fibrillation and significant arteriosclerosis.

Study Type

Observational

Enrollment (Anticipated)

1200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with acute cerebral infarction or transient ischemic attack with non-valvular atrial fibrillation and significant artherosclerosis

Significant atherosclerosis means atherosclerosis in the cerebral, coronary or peripheral arteries according to the judgment of the researchers.

Description

Inclusion Criteria:

  1. Patients with acute cerebral infarction or transient ischemic attack within 14 days of symptom onset based on Last Known Normal Time.
  2. Patients with non-valvular atrial fibrillation including paroxysmal atrial fibrillation which is eligible for treatment with Edoxaban.

  3. Patients with significant atherosclerosis confirmed by imaging tests on the cerebral arteries, coronary arteries, or peripheral arteries and suitable for the use of antiplatelet agents.

    • Significant intracranial internal stenosis confirmed by CTA or MRA
    • A history of coronary artery disease, meaningful findings from CTA or CAG Arterial stenosis
    • Peripheral arterial disease (Ankle-Brachial Index, ABI <0.9, significant stenosis found in lower limb ultrasonography

3) Men and women over 20 years old 4) Patients who voluntarily agreed to register the registry

Exclusion Criteria:

  1. Patients with chronic renal failure (GFR <30 ml / min) or severe liver damage
  2. patients requiring warfarin medication due to prosthetic valve replacement
  3. patients with internal bleeding (active internal bleeding)
  4. bleeding diathesis
  5. History of acute myocardial infarction or received coronary artery procedure within 6 months before screening
  6. Patients who have received or are scheduled to undergo carotid stenting within 1 year
  7. Currently, two or more antiplatelet agents are required due to arteriosclerosis.
  8. Patients whose survival period is expected to be less than 12 months due to serious diseases such as terminal cancer or liver failure
  9. Patients who are scheduled for invasive surgery with possible uncontrolled bleeding, including major surgery
  10. Women who are pregnant or lactating, do not have contraception during the study
  11. A person who is found to be unsuitable for participation in the study due to the clinical laboratory test results or other reasons

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Edoxaban Monotherapy

edoxaban monotherapy without additional antiplatelet therapy in long term stroke prevention.

However, transient additional antiplatelet therapy will be allowed at the discretion of duty physicians.
Drug: Edoxaban Monotherapy
when the patients will be initially registered in this study, duty physicians will make a decision to give additional antiplatelet therapy in addition to standard edoxaban therapy.
Other Names:
  • Edoxaban and antiplatelet combination
Edoxaban and antiplatelet combination
edoxaban plus additional antiplatelet therapy in long term stroke prevention. However, transient cessation of antiplatelet therapy will be allowed at the discretion of duty physicians.
Drug: Edoxaban Monotherapy
when the patients will be initially registered in this study, duty physicians will make a decision to give additional antiplatelet therapy in addition to standard edoxaban therapy.
Other Names:
  • Edoxaban and antiplatelet combination

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MACE (major adverse cardiac event)
Time Frame: 18 months
Duration for first occurrence of major cardiovascular events after patient registration: ischemic stroke, hemorrhagic stroke, myocardial infarction, vascular death
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemorrhagic stroke
Time Frame: 18 months
Duration for first occurrence of hemorrhagic stroke after patient registration
18 months
Stroke
Time Frame: 18 months
Duration for first occurrence of stroke (ischemic and hemorrhagic) after patient registration
18 months
Acute Myocardial Infarction
Time Frame: 18 months
Duration for first occurrence of acute myocardial infarction after patient registration
18 months
Major bleeding
Time Frame: 18 months
Duration for occurrence of major bleeding based on ISTH( International Society on Thrombosis and Haemostasis) after patient registration
18 months
Vascular death
Time Frame: 18 months
Duration for first occurrence of vascular death after patient registration
18 months
Ischemic stroke
Time Frame: 18 months
Duration for first occurrence of ischemic stroke after patient registration
18 months
Net clinical benefit based on reduction in major adverse cardiac event compared to major bleeding events
Time Frame: 18 months
Net clinical benefit based on reduction in major adverse cardiac event compared to major bleeding events
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Collaborators

Samsung Medical Center
Pusan National University Hospital
Chonnam National University Hospital
Korea University Guro Hospital
Korea University
Kyungpook National University Hospital
Chung-Ang University Hosptial, Chung-Ang University College of Medicine
Ewha Womans University
Keimyung University Dongsan Medical Center
Chungnam National University Hospital
Dongtan Sacred Heart Hospital
Myongji Hospital
Chonbuk National University
Eulji University Hospital

Investigators

  • Principal Investigator: Sun U. Kwon, MD, PhD, Asan Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 1, 2019

Primary Completion (ANTICIPATED)

August 31, 2023

Study Completion (ANTICIPATED)

February 28, 2024

Study Registration Dates

First Submitted

June 24, 2019

First Submitted That Met QC Criteria

July 3, 2019

First Posted (ACTUAL)

July 8, 2019

Study Record Updates

Last Update Posted (ACTUAL)

October 14, 2019

Last Update Submitted That Met QC Criteria

October 10, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Add-on_001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Atrial Fibrillation

Clinical Trials on Edoxaban Monotherapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Gambia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe