Dabigatran for Mitral Stenosis Atrial Fibrillation

NCT ID: NCT04045093

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

370 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-22

Study Completion Date

2027-09-30

Brief Summary

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Atrial fibrillation (AF) is the most common sustained cardiac arrythmia encountered in clinical practice and patients suffer from this are at increased risk of ischemic stroke and systemic thromboembolism due to the formation and embolism of left atrial thrombi. Current international guidelines recommend non-vitamin K oral anticoagulants (NOACs) for stroke prevention amongst these patients with non-valvular atrial fibrillation (AF) at significant ischemic stroke risk, given the superior safety and comparable efficacy of NOACs over warfarin. However, the safety and efficacy of NOACs had not been evaluated in AF patients with underlying mitral stenosis (MS) thereby the currently recommended stroke prevention strategy remains warfarin therapy for AF patients with underlying MS. A local study is initiated to compare efficacy and safety of Dabigatran with Warfarin therapy in AF patients with moderate to severe MS.

Detailed Description

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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 was 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. Nonetheless off-label use of NOACs in patients with MS is not uncommon in the real world practice.

This is of particular importance for Asian AF patients, in whom MS remains relatively prevalent despite a declining trend. More importantly, the much higher baseline risk of intracranial haemorrhage and apparently higher ischemic stroke risk in Asian populations potentially undermine the benefits of Warfarin therapy. On the other hand, the efficacy and safety of NOACs compared with Warfarin appear to be even higher in Asian population than the non-Asian population as shown in sub-analyses pivotal randomised control trials as well as in the real world evidence. 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 MS.

After providing written informed consent, study participants from participating local centres 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. In a year of individual study period, vital signs, laboratory blood check and adverse events will be monitored, and primary and secondary outcomes will be assessed. The estimated sample size is approximately 370 participants. On addition, a subgroup of patients up to 10% of the target sample size will be invited for an one-time non-invasive magnetic resonance imaging (MRI) for assessment of any intra-cardiac thrombus.

The results will be an important contribution to the stroke prevention strategy for patients with MS 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.

Conditions

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Atrial Fibrillation Mitral Stenosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective study with randomization in 1:1 ratio
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Dabigatran etexilate

Subjects randomized into this group will be prescribed with either Dabigatran 150mg or Dabigatran 110mg (twice daily) according to creatinine clearance level) for stroke prevention.

Group Type EXPERIMENTAL

Dabigatran etexilate

Intervention Type DRUG

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.

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.

Group Type ACTIVE_COMPARATOR

Warfarin

Intervention Type DRUG

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.

Interventions

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Dabigatran etexilate

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.

Intervention Type DRUG

Warfarin

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.

Intervention Type DRUG

Other Intervention Names

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Pradaxa

Eligibility Criteria

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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
* 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 mechanical 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
* 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 than atrial fibrillation
* Uncontrolled hypertension (systolic blood pressure \> 180mmHg and/or diastolic blood pressure \> 100mmHg)
* Estimated creatinine clearance ≤ 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The University of Hong Kong

OTHER

Sponsor Role lead

Responsible Party

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Wong Chun Ka

Clinical Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Siu Han Jo Jo Hai, Bachelor

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

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The University of Hong Kong / Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status

Countries

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Hong Kong

References

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Zhou M, Chan EW, Hai JJ, Wong CK, Lau YM, Huang D, Lam CC, Tam CCF, Wong YTA, Yung SYA, Chan KWK, Feng Y, Tan N, Chen JY, Yung CY, Lee KL, Choi CW, Lam H, Ng A, Fan K, Jim MH, Yiu KH, Yan BP, Siu CW. Protocol, rationale and design of DAbigatran for Stroke PreVention In Atrial Fibrillation in MoDerate or Severe Mitral Stenosis (DAVID-MS): a randomised, open-label study. BMJ Open. 2020 Sep 25;10(9):e038194. doi: 10.1136/bmjopen-2020-038194.

Reference Type DERIVED
PMID: 32978200 (View on PubMed)

Other Identifiers

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DAMS-01

Identifier Type: -

Identifier Source: org_study_id