- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04045093
Dabigatran for Mitral Stenosis Atrial Fibrillation
Rationale and Design of Dabigatran for Mitral Stenosis Atrial Fibrillation Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
While the stroke risk amongst AF patients appears heterogeneous, patients with underlying valvular heart diseases particularly MS are at very high risk for stroke if left un-anticoagulated. However, this group of patients were typically excluded in randomized control trials. As a result, current international guidelines for management of AF do not recommend NOACs for stroke prevention in AF patients with underlying moderate or severe MS.
In a stark contrast to developed countries, mitral stenosis remains prevalent in many Asian countries. Together with the much higher intracranial haemorrhage risk in Asians on Warfarin, NOACs appear to be a very attractive and promising alternative. Nonetheless off-label use of NOACs in patients with MS is not uncommon in the real world practice. This study refers as a prospective, randomized, open-label trial with blinded end-point adjudication, aiming at evaluating the safety and efficacy of Dabigatran for stroke prevention in AF patients with underlying moderate or severe mitral stenosis.
Subjects enrolled in this study will be randomized into 2 groups in a 1:1 ratio, to receive either Dabigatran (150mg or 110mg according to creatinine clearance level, twice daily) or Warfarin (targeting in the international normalized ratio (INR) range 2-3) in an open-label design. Primary and secondary outcomes will be assessed, including ischemic stroke, systemic embolism, haemorrhagic stroke, intracranial haemorrhage, major bleeding and death. The estimated sample size is approximately 686 participants.
The results will contribute to the stroke prevention strategy for patients with mitral stenosis and may be immediately translatable to real clinical practice. Ultimately, this study will provide the necessary evidence for establishing universal guidelines for this group of patients.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Chun Ka Wong, Clinical Assistant Professor
- Phone Number: +852-22553597
- Email: wongeck@hku.hk
Study Locations
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Hong Kong, Hong Kong
- Recruiting
- Queen Mary Hospital
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Contact:
- Chun Ka Wong, Clinical Assistant Professor
- Phone Number: +852-22553597
- Email: wongeck@hku.hk
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients with atrial fibrillation documented with standard 12-lead ECG documented atrial fibrillation on the day of screening or randomization
- Patients with age 18 years old or above
- Patients with moderate or severe mitral stenosis, i.e. mitral valvular area (MVA) ≤ 2.5cm2
- Patients should be able to provide a written informed consent
- Patients should have all 4 inclusion-criteria fulfilled to be qualified for the study
Exclusion Criteria:
- Patients with prosthetic valve, or with active endocarditis
- Patients with planned valvular intervention within 1 year
- Patients with left atrial appendage occlusive device
- Patients with planned AF ablation
- Patients with history of intracranial, intraocular, spinal, or retroperitoneal bleeding
- Unexplained anemia (haemoglobin level <10g/dL) or thrombocytopenia (platelet count <100x10*9/L)
- Need for anticoagulant therapy of disorders other than atrial fibrillation
- Patients receiving antiplatelet therapy for disorders other an atrial fibrillation
- Uncontrolled hypertension (systolic blood pressure >180mmHg and/or diastolic blood pressure >100mmHg)
- Estimated creatinine clearance equal to or less than 30mL/min
- Liver dysfunction of Child Pugh stage B or C
- Women who are pregnant or of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study
- Patients considered unreliable by the investigator or have a life expectancy less than 1 year because of concomitant disease, or has any condition, which in the opinion of the investigator, would not allow safe participation in the study (e.g. drug addiction, alcohol abuse)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dabigatran etexilate
Subjects randomized into this group will be prescribed with either Dabigatran 150mg or Dabigatran 110mg (twice daily) according to creatinine clearance level, twice daily) for stroke prevention.
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Subjects will be randomized into 2 groups in a 1:1 ratio, to receive either Dabigatran or Warfarin for stroke prevention, in a open-label design.
Other Names:
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Active Comparator: Warfarin
Subjects randomized into this group will be prescribed with Warfarin with dosage adjustment according to INR level (targeting to INR 2-3) for stroke prevention.
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Subjects will be randomized into 2 groups in a 1:1 ratio, to receive either Dabigatran or Warfarin for stroke prevention, in a open-label design.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Stroke
Time Frame: 1 year
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It is defined as a neurological deficit of sudden onset that persisted for more than 24 hours and corresponded to a vascular territory that cannot be explained by other causes.
It will be further classified as ischemic stroke and haemorrhagic stroke according to computerized axial tomography or magnetic resonance imaging of the brain.
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1 year
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Systemic embolism
Time Frame: 1 year
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It is defined as an acute vascular occlusion of an extremity or organ other than the brain, documented by imaging, surgery, and/or autopsy.
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1 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ischemic stroke
Time Frame: 1 year
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It is diagnosed with computerized axial tomography or magnetic resonance imaging of the brain.
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1 year
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Haemorrhagic stroke
Time Frame: 1 year
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It is diagnosed with computerized axial tomography or magnetic resonance imaging of the brain.
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1 year
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Intracranial haemorrhage
Time Frame: 1 year
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It consists of haemorrhagic stroke (intracerebral haemorrhage and cerebellar haemorrhage), subdural haemorrhage, and subarachnoid haemorrhage, and will be confirmed with computerized axial tomography or magnetic resonance imaging of the brain.
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1 year
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Major bleeding
Time Frame: 1 year
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It is defined as a drop in the haemoglobin level of at least 2g/dL, transfusion of at least 2 units of blood, or symptomatic bleeding in a critical area or organ.
Life-threatening bleeding includes fatal bleeding, symptomatic intracranial bleeding, bleeding with a haemoglobin drop of at least 5g/dL, or bleeding requiring transfusion of at least 4 units of blood or inotropic agents or requiring surgery.
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1 year
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Death
Time Frame: 1 year
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It is defined as medically certified cessation of life.
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1 year
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Chun Ka Wong, Clinical Assistant Professor, The University of Hong Kong
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Pathological Conditions, Anatomical
- Arrhythmias, Cardiac
- Heart Valve Diseases
- Atrial Fibrillation
- Constriction, Pathologic
- Mitral Valve Stenosis
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protease Inhibitors
- Antithrombins
- Serine Proteinase Inhibitors
- Anticoagulants
- Dabigatran
- Warfarin
Other Study ID Numbers
- NOAC Dabi MSAF protocol_v.2.1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
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