ClinicalTrials.gov
ClinicalTrials.gov Menu

Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban In Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure (ADRIFT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03273322
Recruitment Status : Recruiting
First Posted : September 6, 2017
Last Update Posted : September 20, 2017
Sponsor:
Collaborators:
Action Research Group
Bayer
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
Evaluation of 2 doses of rivaroxaban (10 and 15 mg) compared to dual anti platelet therapy (aspirin+clopidogrel) after left atrial appendage closure. The patients will be assessed at 10 and 90 days: central laboratory hemostasis analysis and clinical events assessment.

Condition or disease Intervention/treatment Phase
Atrial Fibrillation Atrial Appendage Hemorrhage Drug: Rivaroxaban 10 mg qd Drug: Rivaroxaban 15 mg qd Drug: DAPT Phase 2 Phase 3

Detailed Description:

Data on antithrombotic therapy after Left Atrial Appendage Closure (LAAC) are scarce and no randomized evaluation has been performed to demonstrate what is the best antithrombotic strategy following LAAC. LAAC is classically associated with a 6-week period of anticoagulation with warfarin + aspirin followed by once daily clopidogrel (75 mg) + aspirin (81-325 mg) until the 6 months visit, then aspirin alone is continued indefinitely, as tested in patients without contraindication for anticoagulation in the pivotal Watchman trials. LAAC is mostly used in Europe as an alternative to warfarin anticoagulation when patients have a contraindication to or are unsuitable for warfarin anticoagulation. The classic regimen is not applicable and believed to be too risky in such frail patients. These patients usually receive a regimen of daily clopidogrel + aspirin followed by single antiplatelet therapy (most frequently used treatment). Some patients receive oral anticoagulation without aspirin, including NOAC anticoagulation. Rivaroxaban is a tempting strategy for anticoagulation following LAAC in atrial fibrillation (AF) patients. The dose needs first to be carefully evaluated the trial propose a dose ranging study in patients who have undergone successful LAAC.

The study will evaluate two different Rivaroxaban regimen (10 or 15 mg a day) in comparison to dual antiplatelet therapy (DAPT) (aspirin+clopidogrel : control arm representing standard of care) after successful LAAC. The aim is to investigate whether rivaroxaban could provide correct anticoagulation levels and adequately suppress coagulation activation after LAAC.

The patient will be enrolled after left atrial appendage closure before discharge. The randomization is 1/1/1 between the 3 groups : rivaroxaban 10mg a day, rivaroxaban 15 mg a day and aspirin 75mg + clopidogrel 75 mg a day. At 10 and 90 days, the patients will be sampled for biological assessment : Prothrombin fragments 1+2, Factor Xa inhibitory activity, Russel Viper venom enzyme assay, thrombin anti-thrombin (TAT) complex, D-Dimers, Prothrombin time (Neoplastin) and plasma von Willebrand factor (vWf) Ag level

After 90 days, the patient will end his/her participation in the trial. Clinical endpoints (death, MI, Stroke, TIA, systemic embolism, extracranial major bleeding or clinically relevant non major bleeding) at 90 days will be assessed by a clinical endpoint committee. Central echographic laboratory will review all 90 days transesophageal echocardiography (TEE) to detect the presence of thrombus or peri-device leak.

The study is open-label. Central laboratory, clinical endpoint committee and echographic core laboratory is blinded to randomization arm.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban In Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure: The Randomized ADRIFT Study
Actual Study Start Date : September 13, 2017
Estimated Primary Completion Date : September 23, 2018
Estimated Study Completion Date : December 23, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Rivaroxaban
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1: Rivaroxaban 10 mg qd
Rivaroxaban 10 mg, 1 tablet a day, from randomization to Day 90 should be taken between 8 and 10 AM
Drug: Rivaroxaban 10 mg qd
10mg qd
Experimental: 2: Rivaroxaban 15 mg qd

Rivaroxaban 15 mg, 1 tablet a day, from randomization to Day 90

should be taken between 8 and 10 AM

Drug: Rivaroxaban 15 mg qd
15mg qd
Active Comparator: 3: DAPT
Aspirin 75 mg, 1 a day Clopidogrel 75 mg, 1 tablet a day from randomization to Day 90 should be taken between 8 and 10 AM
Drug: DAPT
Aspirin 75 mg qd + Clopidogrel 75 mg qd



Primary Outcome Measures :
  1. Measure of prothrombin fragment 1 + 2 [ Time Frame: at Day 10 ]
    Measure of prothrombin fragment 1 + 2 at Day 10 (2 to 4 hours after last intake : concentration peak)


Secondary Outcome Measures :
  1. Measure of prothrombin fragment 1 + 2 [ Time Frame: at Day 90 ]
    Measure of prothrombin fragment 1 + 2 at Day 90 (2 to 4 hours after last intake : concentration peak)

  2. Factor Xa inhibitory activity [ Time Frame: at Day 10 ]
    Factor Xa inhibitory activity

  3. Russel Viper venom enzyme assay [ Time Frame: at Day 90 ]
    Russel Viper venom enzyme assay

  4. TAT complex [ Time Frame: at Day 10 ]
    TAT complex

  5. TAT complex [ Time Frame: at Day 90 ]
    TAT complex

  6. D-Dimers [ Time Frame: at Day 10 ]
    D-Dimersand at peak, 2 to 4 hours after treatment intake

  7. D-Dimers [ Time Frame: at Day 90 ]
    D-Dimersand at peak, 2 to 4 hours after treatment intake

  8. Prothrombin time (Neoplastin) [ Time Frame: at Day 10 ]
    Prothrombin time (Neoplastin)

  9. Prothrombin time (Neoplastin) [ Time Frame: at Day 90 ]
    Prothrombin time (Neoplastin)

  10. Plasma vWf Ag level [ Time Frame: at Day 10 ]
    plasma vWf Ag level treatment intake

  11. Plasma vWf Ag level [ Time Frame: at Day 90 ]
    plasma vWf Ag level treatment intake

  12. Haemorrhagic stroke and bleeding will be safety outcomes TEE with central core lab reading: presence of thrombus, peri-device leak [ Time Frame: at Day 90 ]
    Haemorrhagic stroke and bleeding will be safety outcomes 3-month TEE with central core lab reading: presence of thrombus, peri-device leak

  13. Composite clinical endpoint combining all clinical outcomes : Death, MI, stroke, TIA, [ Time Frame: at Day 90 ]
  14. Death (any cause) [ Time Frame: at Day 90 ]
    Death (any cause) assessed individually and combined at other outcomes

  15. Myocardial infarction (MI) [ Time Frame: at Day 90 ]
    Myocardial infarction (MI) assessed individually and combined at other outcomes

  16. Stroke (ischaemic stroke, haemorrhagic stroke) [ Time Frame: at Day 90 ]
    Stroke (ischaemic stroke, haemorrhagic stroke) assessed individually and combined at other outcomes

  17. Transient Ischemic Attack (TIA) [ Time Frame: at Day 90 ]
    Transient Ischemic Attack (TIA) assessed individually and combined at other outcomes

  18. Systemic embolism [ Time Frame: at Day 90 ]
    Systemic embolism assessed individually and combined at other outcomes

  19. Extracranial major bleeding or clinically relevant non major bleeding (ISTH definition) [ Time Frame: at Day 90 ]
    Extracranial major bleeding or clinically relevant non major bleeding (ISTH definition) assessed individually and combined at other outcomes



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women ≥18 years of age
  • Patients who underwent a clinically successful LAAC procedure (device implanted without procedural or bleeding complication). LAAC may have been indicated for patients contraindicated or unsuitable for long-term Vitamin K antagonists (VKA) anticoagulation.
  • AF (permanent or persistent or paroxysmal) patients irrespective of prior antithrombotic treatment are eligible for randomization.
  • Written informed consent by the patient or designee if the patient is unable to consent
  • Patients affiliated to the French social security system

Exclusion Criteria:

  • Creatinine clearance <30 mL / min (Cockcroft formula).
  • Dialysis.
  • Mechanical heart valves or valvular disease requiring surgery or interventional procedure
  • Planned Ablation of AF during follow up period
  • Mandatory indication for dual antiplatelet therapy (e.g. recent stent) or single anti-platelet treatment (SAPT) (e.g. high coronary risk).
  • Any contra-indication or known allergy to aspirin or clopidogrel or rivaroxaban.
  • Any mandatory indication for anticoagulation for a reason other than AF (e.g. Pulmonary embolism)
  • Ongoing major bleeding or complicated or recent (<72hours) major surgery
  • Known large oesophageal varices or decompensated liver disease (unless a documented positive opinion of a gastro-enterologist)
  • Severe thrombocytopenia (<50,000/ml) after referral to haematologist to confirm or not contraindication
  • Recent myocardial infarction (<6 weeks).
  • Recent cerebro-vascular event (CVE) or transient ischemic attack (<6 weeks) after evaluation of stroke vs bleeding risk by the referring neurologist.
  • Recent Intracranial bleeding (< 6 months): these patients will be evaluated by a neurologist as these patients may be considered at higher stroke risk. Neurologist may consider that the LAAC procedure with a short (90 days) period of anticoagulation or antiplatelet therapy as tested in the protocol is a preferable option (in that case intracranial hemorrhage (ICH) will not be considered as a contraindication).
  • Prasugrel or ticagrelor concomitant use
  • Participating in an investigational drug or another device trial within the previous 30 days.
  • High likelihood of being unavailable for follow-up or psycho-social condition making study participation impractical.
  • Woman with child bearing potential who do not use an efficient method of contraception.
  • positive serum or urine pregnancy test for woman with child bearing potential
  • Pregnancy or within 48 hours post-partum or breast feeding women
  • Patient under legal protection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03273322


Contacts
Contact: Gilles MONTALESCOT, MD, PhD +331 42163006 Gilles.montalescot@aphp.fr

Locations
France
Institut de Cardiologie - Hôpital Pitié-Salpêtrière Recruiting
Paris, France, 75013
Contact: Gilles MONTALESCOT, MD, PhD    +331 42163006    Gilles.montalescot@aphp.fr   
Contact: Delphine BRUGIER, PhD    +331 42162918    delphine.brugier@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Action Research Group
Bayer

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03273322     History of Changes
Other Study ID Numbers: P161102J
First Posted: September 6, 2017    Key Record Dates
Last Update Posted: September 20, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Left atrial appendage closure
Rivaroxaban
Dual antiplatelet therapy
Anticoagulation
Stroke prevention

Additional relevant MeSH terms:
Atrial Fibrillation
Hemorrhage
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Rivaroxaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants