- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03273322
Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban In Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure (ADRIFT)
Assessment of Dual Antiplatelet Therapy Versus Rivaroxaban In Atrial Fibrillation Patients Treated With Left Atrial Appendage Closure: The Randomized ADRIFT Study
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Paris, France, 75013
- Institut de Cardiologie - Hôpital Pitié-Salpêtrière
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / 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
|
10mg qd
Other Names:
|
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 |
15mg qd
Other Names:
|
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
|
Aspirin 75 mg qd + Clopidogrel 75 mg qd
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
at Day 10
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
at Day 90
|
Factor Xa inhibitory activity at day 10
Time Frame: at Day 10
|
Factor Xa inhibitory activity
|
at Day 10
|
Factor Xa inhibitory activity at day 90
Time Frame: at Day 90
|
Factor Xa inhibitory activity
|
at Day 90
|
Russel Viper venom enzyme assay
Time Frame: at Day 90
|
Russel Viper venom enzyme assay
|
at Day 90
|
TAT complex
Time Frame: at Day 10
|
TAT complex
|
at Day 10
|
TAT complex
Time Frame: at Day 90
|
TAT complex
|
at Day 90
|
D-Dimers
Time Frame: at Day 10
|
D-Dimersand at peak, 2 to 4 hours after treatment intake
|
at Day 10
|
D-Dimers
Time Frame: at Day 90
|
D-Dimersand at peak, 2 to 4 hours after treatment intake
|
at Day 90
|
Prothrombin time (Neoplastin)
Time Frame: at Day 10
|
Prothrombin time (Neoplastin)
|
at Day 10
|
Prothrombin time (Neoplastin)
Time Frame: at Day 90
|
Prothrombin time (Neoplastin)
|
at Day 90
|
Plasma vWf Ag level
Time Frame: at Day 10
|
plasma vWf Ag level treatment intake
|
at Day 10
|
Plasma vWf Ag level
Time Frame: at Day 90
|
plasma vWf Ag level treatment intake
|
at Day 90
|
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
|
at Day 90
|
Composite clinical endpoint combining all clinical outcomes
Time Frame: at Day 90
|
Composite clinical endpoint combining all clinical outcomes : Death, MI, stroke, TIA,
|
at Day 90
|
Death (any cause)
Time Frame: at Day 90
|
Death (any cause) assessed individually and combined at other outcomes
|
at Day 90
|
Myocardial infarction (MI)
Time Frame: at Day 90
|
Myocardial infarction (MI) assessed individually and combined at other outcomes
|
at Day 90
|
Stroke (ischaemic stroke, haemorrhagic stroke)
Time Frame: at Day 90
|
Stroke (ischaemic stroke, haemorrhagic stroke) assessed individually and combined at other outcomes
|
at Day 90
|
Transient Ischemic Attack (TIA)
Time Frame: at Day 90
|
Transient Ischemic Attack (TIA) assessed individually and combined at other outcomes
|
at Day 90
|
Systemic embolism
Time Frame: at Day 90
|
Systemic embolism assessed individually and combined at other outcomes
|
at Day 90
|
Extracranial major bleeding or clinically relevant non major bleeding (ISTH definition) at day 90
Time Frame: at Day 90
|
Extracranial major bleeding or clinically relevant non major bleeding (ISTH definition) assessed individually and combined at other outcomes
|
at Day 90
|
Collaborators and Investigators
Investigators
- Principal Investigator: Gilles MONTALESCOT, MD, PhD, Centre Hospitalier Universitaire Pitié-Salpêtrière Paris
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- P161102J
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
Clinical Trials on Hemorrhage
-
Region StockholmRecruitingRetinal Hemorrhage, Bilateral | Retinal Hemorrhage, Left Eye | Retinal Hemorrhage, Right EyeSweden
-
Al Hadi HospitalCompletedDiabetic Vitreous HemorrhageKuwait
-
Massachusetts Eye and Ear InfirmaryCompletedPost-operative HemorrhageUnited States
-
Panhandle Eye Group, LLPRecruitingDiabetic Vitreous HemorrhageMexico
-
Weill Medical College of Cornell UniversityThe Edward Grayson Fund for Retinal ResearchUnknownSubretinal Hemorrhage and Exudative MaculopathyUnited States
-
Tel-Aviv Sourasky Medical CenterIsrael Defense ForcesRecruiting
-
Ain Shams Maternity HospitalUnknownPost Operative HemorrhageEgypt
-
Asan Medical CenterUnknownPost Vitrectomy State | Recurrent Diabetic Vitreous HemorrhageKorea, Republic of
-
University of PisaCompletedPost Operative HemorrhageItaly
-
Cairo UniversityCompletedPost Operative HemorrhageEgypt
Clinical Trials on Rivaroxaban 10 mg qd
-
Kowa Research Institute, Inc.CompletedHyperlipidemiaUnited States
-
NeuroActiva, Inc.CompletedNeurocognitive Disorders | Neurodegenerative Diseases | Cognitive Impairment | Alzheimer Disease | Tauopathies | Mild Cognitive Impairment | Dementia, Vascular | Dementia With Lewy Bodies | Alzheimer Dementia | Cognitive DisorderNew Zealand
-
PfizerCompletedDiabetes Mellitus, Type 2United States, Colombia, Spain, Germany, Sweden, Italy
-
Eisai Inc.CompletedObesityUnited States
-
Lexicon PharmaceuticalsCompletedRheumatoid ArthritisUnited States
-
PfizerTerminatedParkinson's Disease With Motor FluctuationsUnited States
-
Boehringer IngelheimCompletedSchizophreniaUnited States, Taiwan, Germany, Japan, Canada
-
PfizerWithdrawnUlcerative ColitisUnited States
-
Eisai Inc.Completed
-
PfizerCompletedWeight Management | Treatment Of ObesityCanada, United States, Bulgaria, Spain, Mexico, India, Puerto Rico