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Atrial FibrillationPhase 4DARING-AFNCT02666157

Comparison of Efficacy and Safety Among Dabigatran, Rivaroxaban, and Apixaban in Non-Valvular Atrial Fibrillation

A Phase 4 study testing Dabigatran etexilate, Rivaroxaban and Apixaban in people with Atrial Fibrillation, run by National Cheng-Kung University Hospital at 5 sites in Taiwan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

1. The recent development of novel oral anticoagulants (NOACs), including direct thrombin inhibitor (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), could potentially overcome many drawbacks of warfarin, and might provide a safer, and even more effective and convenient alternative approach… Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Atrial Fibrillation
What is being tested?
Dabigatran etexilate, Rivaroxaban and Apixaban
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3,672 participants
Where
5 sitesTaiwan
Study dates
Jan 2016to Dec 2018
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Inclusion Criteria: Known AF (paroxysmal or persistent/ permanent) who are suitable and ready for NOAC treatment plus at least one of the following criteria

  • Prior ischemic stroke, transient ischemic accident or systemic embolism
  • Left ventricular ejection fraction ≤40% (documented by echocardiography or contrast ventriculography)
  • Symptomatic congestive heart failure (≥ New York Heart Association Functional Class 2) within 6 months before screening
  • Age ≥75 years
  • Age ≥65 but <75 years with diabetes mellitus, hypertension or coronary artery disease

Exclusion Criteria: Subjects are excluded if they have at least one of the following situations before screening:

  • Known severe (i.e. hemodynamically significant) mitral stenosis regardless of having received operation
  • Time elapsed from the onset of stroke ≤7 days
  • Bleeding tendency
  • Creatinine clearance rate ≤30 mL/min
  • Known active liver disease (persistent elevation of alanine aminotransferase, aspartate transaminase or alkaline phosphatase ≥3 × upper normal limit; or advanced liver cirrhosis ≥Pugh B)
  • Pregnancy
  • Recent documented active malignancy or radiation therapy (≤6 months) and not expected to survive 3 years
  • Unwilling to give informed consent
  • Conditions other than AF that required anticoagulation
  • Anemia (hemoglobin level <90 g/L) or thrombocytopenia (platelet count <100 × 109/L)
  • Persistent uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >100 mmHg)
  • Active infective endocarditis
  • Patients considered unreliable by the investigator or have a life expectancy less than the expected duration of the trial because of concomitant disease, or has any condition which in the opinion of the investigator, would not allow safe participation in the study

Trial locations and contacts

5 sites in 1 country.

Ting-Hsing Chao, MD contact

886-6-2353535 ext. 2382

chaoth@mail.ncku.edu.tw

5 sites in 1 country

Taiwan5 sites, 5 recruiting

  • National Cheng Kung University Hospital Dou-Liou Branch

    Dou-Liou City, 640

    Yang-Cheh Hsueh, MD, 886-5-5332121 ext. 5101, p308378@dou6.hosp.ncku.edu.tw

    Yang-Cheh Hsueh, MD

    Not yet recruiting

  • E-DA Hospital

    Kaohsiung City, 824

    Wei-Kung Tseng, MD and PhD, 886-7-6150011 ext. 5005, arthurtseng@me.com

    Wei-Kung Tseng, MD and PhD

    Not yet recruiting

  • National Cheng Kung University Hospital

    Tainan, Tainan City, 704

    Ting-Hsing Chao, MD, 886-6-2353535 ext. 2382, chaoth@mail.ncku.edu.tw

    Ting-Hsing Chao, MD

    Recruiting

  • Tainan Hospital Ministry of Health and Welfare

    Tainan, Tainan City, 704

    Li-Dan Yang, MD, 886-6-2200055 ext. 9, litannyang@yahoo.com.tw

    Li-Dan Yang, MD

    Not yet recruiting

  • Tainan Municipal Hospital

    Tainan, 701

    I-Chih Chen, MD, 886-6-2609926 ext. 212045, ichih1230@yahoo.com.tw

    I-Chih Chen, MD

    Recruiting

Other trials in Taiwan

About this study

Official title: Comparison of Efficacy and Safety Among DAbigatran, RIvaroxaban, and ApixabaN in Patients HavinG Non-Valvular Atrial Fibrillation in Taiwan (DARING-AF Study)

  1. The recent development of novel oral anticoagulants (NOACs), including direct thrombin inhibitor (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), could potentially overcome many drawbacks of warfarin, and might provide a safer, and even more effective and convenient alternative approach to warfarin in non-valvular atrial fibrillation (NVAF), especially in Asians.
  2. According to the results of a meta-analysis comparing Asians and non-Asians, NOACs are preferentially indicated in Asians in terms of both efficacy and safety.
  3. There is no randomized controlled trial with sufficient power to directly compare the efficacy and safety among NOACs in NVAF, not to speak of Asians and Chinese.
  4. Indirect comparisons are only based on observation with a lot of limitations such as heterogeneous background characteristics, difference in study design, and diversity in time within therapeutic range in control group. The findings from indirect comparisons are not conclusive but only hypothesis-generating.
  5. This investigator-initiated prospective randomized open blinded end-point clinical trial will directly compare the efficacy and safety among 3 NOACs in patients with NVAF in Taiwan. We hypothesize that rivaroxaban or apixaban is non-inferior to dabigatran in terms of the efficacy.
Read the detailed description
  1. participants
  2. eligible participants are randomly assigned to dabigatran, rivaroxaban, or apixaban with allocation ratio of 1:1:1
  • Patients are randomly assigned to receive dabigatran (110 or 150 mg twice daily), rivaroxaban (15 or 20 mg daily), or apixaban (5 mg twice daily) with dosage and frequency approved by the Ministry of Health and Welfare, Taiwan. Reduced doses (dabigatran 110 mg twice daily, rivaroxaban 10 or 15 mg daily, or apixaban 2.5 mg twice daily) are allowed in a subset of patients with one or more of the following criteria: an age of at least 80 years, a body weight of no more than 60 kg, a serum creatinine level ≥1.5 mg per deciliter (133 μmol per liter) or creatinine clearance around 30 to 49 ml per minute)
  1. blood sampling, genotyping, and measurement of biomarkers
  2. bood samples (13 mL) from peripheral veins in all study subjects at baseline and 10 mL 3 months later, and stored for enzyme-linked immunosorbent assay as well as genotyping
  3. outcome follow-up a. clinical follow-up is performed and clinical outcomes are obtained by clinic visit, telephone call or direct contact with participants or subjects' family quarterly after treatment for 2 times, then every 6 months
Being tested
Dabigatran etexilate, Rivaroxaban, Apixaban
Keywords
atrial fibrillation, stroke, systemic embolism, bleeding, oral anticoagulant
Medical subject headings
Atrial Fibrillation, Stroke, Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dabigatran etexilateDrug

    Also called Pradaxa

    this drug is administered twice per day for the entire study period

  • RivaroxabanDrug

    Also called Xarelto

    this drug is administered once per day for the entire study period

  • ApixabanDrug

    Also called Eliquis

    this drug is administered twice per day for the entire study period

Study groups in NCT02666157
Study groupRoleWhat they receive
DabigatranActive comparatororal dabigatran etexilate capsule 110 or 150 mg (110 mg in specific population) bid for entire study period
Receives: Drug: Dabigatran etexilate
RivaroxabanActive comparatororal rivaroxaban film-coated tablet 15 or 20 mg (10 or 15 mg in specific population) qd for entire study period
Receives: Drug: Rivaroxaban
ApixabanActive comparatororal apixaban 5 mg (2.5 mg in specific population) bid for entire study period
Receives: Drug: Apixaban

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to the occurrence of the major embolic events

    a composite of stroke (ischemic or hemorrhagic), transient ischemic attack or systemic embolism

    Measured: up to 36 months

Secondary outcomes (3)

  1. Time to the occurrence of the major embolic events and death

    a composite of all stroke (including hemorrhagic), systemic embolism, and death

    Measured: up to 36 months

  2. Time to the occurrence of the major embolic and vascular events

    a composite of all stroke, systemic embolism, pulmonary embolism, acute myocardial infarction, and vascular death

    Measured: up to 36 months

  3. Time to the occurrence of all clinically relevant bleeding events

    a composite of major bleeding or clinically relevant non-major bleeding events

    Measured: up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2016 (estimated)
  2. Study startJan 2016
  3. Primary completionDec 2018 (estimated)
  4. Study completionDec 2018 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
3,672 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02666157
Sponsor's protocol ID
A-BR-104-049
Acronym
DARING-AF
Status last verified
Feb 2016
First submitted
24 Jan 2016
Last updated
17 Feb 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • Chiang CE, Zhang S, Tse HF, Teo WS, Omar R, Sriratanasathavorn C. Atrial fibrillation management in Asia: from the Asian expert forum on atrial fibrillation. Int J Cardiol. 2013 Mar 20;164(1):21-32. doi: 10.1016/j.ijcard.2011.12.033. Epub 2012 Jan 10.

    PubMed 22240753

  • Chiang CE, Wang KL, Lip GY. Stroke prevention in atrial fibrillation: an Asian perspective. Thromb Haemost. 2014 May 5;111(5):789-97. doi: 10.1160/TH13-11-0948. Epub 2014 Feb 6.

    PubMed 24500243

  • Lin LJ, Cheng MH, Lee CH, Wung DC, Cheng CL, Kao Yang YH. Compliance with antithrombotic prescribing guidelines for patients with atrial fibrillation--a nationwide descriptive study in Taiwan. Clin Ther. 2008 Sep;30(9):1726-36. doi: 10.1016/j.clinthera.2008.09.010.

    PubMed 18840379

  • Chang CH, Yang YH, Chen JH, Lin LJ. Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation in Taiwan. Thromb Res. 2014 May;133(5):782-9. doi: 10.1016/j.thromres.2014.02.024. Epub 2014 Mar 3.

    PubMed 24642004

  • Lip GY, Wang KL, Chiang CE. Non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in Asian patients with atrial fibrillation: time for a reappraisal. Int J Cardiol. 2015 Feb 1;180:246-54. doi: 10.1016/j.ijcard.2014.11.182. Epub 2014 Nov 26.

    PubMed 25463377

  • Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30.

    PubMed 19717844

  • Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sep 8;365(10):883-91. doi: 10.1056/NEJMoa1009638. Epub 2011 Aug 10.

    PubMed 21830957

  • Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27.

    PubMed 21870978

  • Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Spinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104. doi: 10.1056/NEJMoa1310907. Epub 2013 Nov 19.

    PubMed 24251359

  • Hori M, Connolly SJ, Zhu J, Liu LS, Lau CP, Pais P, Xavier D, Kim SS, Omar R, Dans AL, Tan RS, Chen JH, Tanomsup S, Watanabe M, Koyanagi M, Ezekowitz MD, Reilly PA, Wallentin L, Yusuf S; RE-LY Investigators. Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation. Stroke. 2013 Jul;44(7):1891-6. doi: 10.1161/STROKEAHA.113.000990. Epub 2013 Jun 6.

    PubMed 23743976

  • Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014 Mar 15;383(9921):955-62. doi: 10.1016/S0140-6736(13)62343-0. Epub 2013 Dec 4.

    PubMed 24315724

  • Lip GY, Larsen TB, Skjoth F, Rasmussen LH. Indirect comparisons of new oral anticoagulant drugs for efficacy and safety when used for stroke prevention in atrial fibrillation. J Am Coll Cardiol. 2012 Aug 21;60(8):738-46. doi: 10.1016/j.jacc.2012.03.019. Epub 2012 May 9.

    PubMed 22575324

  • Ezekowitz MD, Connolly S, Parekh A, Reilly PA, Varrone J, Wang S, Oldgren J, Themeles E, Wallentin L, Yusuf S. Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran. Am Heart J. 2009 May;157(5):805-10, 810.e1-2. doi: 10.1016/j.ahj.2009.02.005.

    PubMed 19376304

  • ROCKET AF Study Investigators. Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF study. Am Heart J. 2010 Mar;159(3):340-347.e1. doi: 10.1016/j.ahj.2009.11.025.

    PubMed 20211293

  • Lopes RD, Alexander JH, Al-Khatib SM, Ansell J, Diaz R, Easton JD, Gersh BJ, Granger CB, Hanna M, Horowitz J, Hylek EM, McMurray JJ, Verheugt FW, Wallentin L; ARISTOTLE Investigators. Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J. 2010 Mar;159(3):331-9. doi: 10.1016/j.ahj.2009.07.035.

    PubMed 20211292

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dabigatran etexilate, Rivaroxaban and Apixaban in people with Atrial Fibrillation, run by National Cheng-Kung University Hospital at 5 sites in Taiwan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 17 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Ting-Hsing Chao, MD (886-6-2353535 ext. 2382, chaoth@mail.ncku.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to the occurrence of the major embolic events (time frame: up to 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02666157, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2016.

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