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Assessment of Quitting Versus Using Aspirin Therapy In Patients Treated With Oral Anticoagulation for Atrial Fibrillation With Stabilized Coronary Artery Disease (AQUATIC)

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ClinicalTrials.gov Identifier: NCT04217447
Recruitment Status : Not yet recruiting
First Posted : January 3, 2020
Last Update Posted : January 7, 2020
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
University Hospital, Brest

Brief Summary:
  • Long-term aspirin (ASA) is the standard recommended antithrombotic therapy in patients with stable coronary artery disease (CAD), especially following stenting (Class I, Level A).
  • Long-term oral anticoagulation (OAC) is the standard antithrombotic therapy in patients with atrial fibrillation (AF) associated with one or more risk factor for stroke (Class I, Level A).
  • During the first year following acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), several studies evaluating the combination of OAC treatment and antiplatelet therapy are either already published or ongoing.
  • At distance of the index ACS and/or PCI, patients with stable CAD and concomitant AF remain at particular high-risk of ischemic (3 to 4 times higher as compared to patients with stable CAD without AF) and bleeding events. Antithrombotic management of these patients is subsequently highly challenging in clinical practice. The European task force suggests that the use of a full-dose anticoagulant monotherapy without any antiplatelet therapy should be the default strategy in such patients with both, AF and stable CAD.
  • However, evidences are sparse and weak to support such a strategy (only observational studies with many biases) and no randomized trial has assessed this question. These patients, especially those at high-risk of recurrent ischemic events (post- ACS, diabetes, multivessel CAD…) may benefit from the combination of OAC and aspirin at long-term. Indeed the crude event rate of ischemic events is much higher than the crude event rate of bleeding in this specific population. Ischemic events are 2 to 3 times more frequent than bleeding in daily practice.
  • The benefit/risk ratio of these two different strategies (ASA in combination with OAC vs. OAC alone) in patients at high-risk of recurrent coronary and vascular events remains unknown. Dual therapy with full-dose anticoagulation and ASA may lead to higher risk of major bleeding, while stopping ASA in stabilized high-risk patients after PCI may lead to poorer outcome regarding ischemic events.
  • The coordinating investigators therefore designed a double blind placebo controlled trial in order to assess the optimal antithrombotic regimen that should be pursued long-life in this subset of patients.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: OAC + Aspirin 100mg od Drug: OAC + placebo of Aspirin 100mg od Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: It's a prospective, randomized, double-blind, placebo controlled, parallel-group, multi-center study.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Assessment of Quitting Versus Using Aspirin Therapy In Patients Treated With Oral Anticoagulation for Atrial Fibrillation With Stabilized Coronary Artery Disease
Estimated Study Start Date : April 2020
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Arm Intervention/treatment
Active Comparator: Experimental group
Patients intaking full-dose OAC + ASA 100mg od
Drug: OAC + Aspirin 100mg od
Patients will receive full-dose of OAC + Aspirin 100mg od during 24 to 48 months (until death or the end of the study : i.e. achievement of 2-year follow-up of the last included patient, maximum of 48-month followup for the first included patient)

Placebo Comparator: Control group
Patients intaking full-dose OAC + Placebo of ASA 100mg od
Drug: OAC + placebo of Aspirin 100mg od
Patients will receive full-dose of OAC + placebo of Aspirin 100mg od during 24 to 48 months (until death or the end of the study : i.e. achievement of 2-year follow-up of the last included patient, maximum of 48-month followup for the first included patient)




Primary Outcome Measures :
  1. Primary efficacy outcome : rate of composite of cardiovascular mortality and thrombotic cardiovascular events [ Time Frame: within 24-48 months ]

    The primary efficacy outcome is the incidence of the adjudicated composite of (within 24-48 months):

    • CV mortality
    • Thrombotic cardiovascular events

      • Myocardial infarction
      • Stroke
      • Any coronary revascularization
      • Systemic embolism
      • Acute limb ischemia

    An Independent Clinical Events Committee (ICEC) will adjudicate all events (ischemic and bleeding events).


  2. Primary safety outcome : rate of major bleeding [ Time Frame: within 24-48 months ]
    The primary safety outcome is the occurrence of major bleeding according to the ISTH (International Society of Thrombosis and Haemostasis) definition


Secondary Outcome Measures :
  1. Secondary efficacy outcomes : rate of composite of CV mortality, MI, stroke; CV mortality; all cause of death; thrombotic cardiovascular events. [ Time Frame: within 24-48 months ]

    The secondary efficacy outcomes are the occurrence of any of the following events:

    • The composite of CV mortality, MI, stroke
    • CV mortality
    • All cause death
    • Thrombotic cardiovascular events:

      • Myocardial infarction
      • Stent thrombosis alone (definite or probable)
      • Stroke (ischemic, hemorrhagic, or stroke of uncertain cause, TIA)
      • Any coronary revascularization
      • Systemic embolism
      • Acute limb ischemia

  2. Secondary safety outcomes : rate of major and clinically relevant non major bleeding [ Time Frame: within 24-48 months ]

    The secondary safety outcome are the occurrence of :

    Major and clinically relevant non major bleeding according to the ISTH definition (ISTH : International Society of Thrombosis and Haemostasis) Major bleeding (TIMI : Thrombolysis in Myocardial Infarction) Major bleeding (BARC ≥3 : Bleeding Academic Research Consensus)




Information from the National Library of Medicine

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

Inclusion Criteria:

  • Patients >18 year-old
  • All patients that need anticoagulation with direct oral anticoagulant (DOAC) or vitamin K antagonist (VKA) for AF (paroxysmal, persistent or permanent) and have a stabilized CAD (free from MI, or coronary revascularization in the past year) but remain at high residual risk of recurrent coronary and vascular events. The use of DOAC will be promoted as recommended by guidelines.
  • Two different categories of patients could be included in the study, i) patients treated at the time of inclusion with the association of OAC and single antiplatelet therapy, it will be tested for them aspirin vs. interruption of antiplatelet therapy ii) patients treated with OAC alone at the time of inclusion, it will be tested for them administration of aspirin vs. no additional treatment with aspirin.
  • High-risk of coronary and vascular event is defined as follow :

    1. History of PCI during an ACS involving placement of ≥1 stent(s) since >1 year.
    2. History of PCI (>1year) outside the context of ACS but with high-risk features of ischemic event recurrences defined as: diabetes, or diffuse multivessel disease (defined by the involvement of the 3 coronary vessels), or chronic kidney disease (creatinine clearance < 50ml/min), or prior stent thrombosis, or complex PCI (defined by: stenting of the last remaining patent coronary artery, left main, at least 3 stents implanted and/or 3 lesions treated, bifurcation with two stents, length of stent >60mm and chronic total coronary occlusion) or the presence of peripheral artery disease (previous limb revascularization bypass or percutaneous angioplasty, previous limb or foot amputation for arterial vascular disease, history of intermittent claudication of peripheral artery stenosis (≥50%) ,previous carotid revascularization or carotid stenosis ≥50%).
  • Women of childbearing potential with effective contraception defined as

    • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation :

      • oral
      • intravaginal
      • transdermal
    • progestogen-only hormonal contraception associated with inhibition of ovulation :

      • oral
      • injectable
      • implantable
    • intrauterine device (IUD)
    • intrauterine hormone-releasing system ( IUS)
    • bilateral tubal occlusion
    • vasectomised partner
    • sexual abstinence

Exclusion Criteria:

  • Any coronary event within a year prior to randomization
  • High risk of bleeding defined as recent (≤6 months) ISTH major bleeding event
  • Constitutional or acquired haemorrhagic disease including gastrointestinal bleeding and thrombocytopenia
  • Planned PCI within the next 6 months after randomization or subject requiring P2Y12 receptor antagonist therapy
  • Stroke within 1 month or any history of hemorrhagic stroke
  • Any contraindication to aspirin (ASA) or any of these excipients or other NSAIDs (hypersensitivity, allergy, active bleeding)
  • Any contraindication to anticoagulant
  • History (s) of asthma induced by the administration of salicylates or substances of close activity (especially NSAIDs)
  • Evolutionary gastroduodenal ulcer
  • Any other gastroduodenal history
  • Severe renal insufficiency
  • Severe hepatic insufficiency
  • Severe, uncontrolled heart failure
  • Lactose intolerance
  • Pregnancy
  • Breastfeeding patients
  • Unable (protected adults : tutorship, curatorship) orunwilling to consent

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): NCT04217447


Contacts
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Contact: Martine GILARD, PhD 2 98 34 75 03 ext +33 martine.gilard@chu-brest.fr
Contact: Marie DURANTI marie.duranti@chu-brest.fr

Locations
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Sponsors and Collaborators
University Hospital, Brest
Bayer
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Responsible Party: University Hospital, Brest
ClinicalTrials.gov Identifier: NCT04217447    
Other Study ID Numbers: 29BRC19.0116
First Posted: January 3, 2020    Key Record Dates
Last Update Posted: January 7, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Brest:
atrial fibrillation
oral anticoagulation
antithrombotic therapy
Additional relevant MeSH terms:
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Atrial Fibrillation
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics