Clinical trial NCT04045093: Dabigatran for Mitral Stenosis Atrial Fibrillation
Official title: Rationale and Design of Dabigatran for Mitral Stenosis Atrial Fibrillation Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Atrial Fibrillation
Mitral Stenosis
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2019-08-05
Enrollment: 370
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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 AF at significant ischemic stroke risk, given the superior safety and comparable efficacy of NOACs over warfarin. However, warfarin therapy remains in the stroke prevention strategy for AF patients with mitral stenosis (MS) as NOACs lack of evidence for safety and efficacy amongst this group of patients. A local study is initiated to compare and evaluate the safety and efficacy among the two groups of anticoagulants - NOACs and traditional Warfarin therapy - in AF patients with underlying moderate to severe MS.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Stroke
timeFrame: 1 year
measure: Systemic embolism
timeFrame: 1 year
Secondary outcomes:
measure: Ischemic stroke
timeFrame: 1 year
measure: Haemorrhagic stroke
timeFrame: 1 year
measure: Intracranial haemorrhage
timeFrame: 1 year
measure: Major bleeding
timeFrame: 1 year
measure: Death
timeFrame: 1 year
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
Study officials:
affiliation: The University of Hong Kong
name: Chun Ka Wong, Clinical Assistant Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.