Ignite Creation Date:
2024-05-06 @ 2:06 PM
Last Modification Date:
2024-10-26 @ 1:25 PM
Study NCT ID:
NCT04217447
Status:
RECRUITING
Last Update Posted:
2023-10-02
First Post:
2019-12-31
Brief Title:
Assessment of Quitting Versus Using Aspirin Therapy In Patients Treated With Oral Anticoagulation for Atrial Fibrillation or Other Indication With Stabilized Coronary Artery Disease
Sponsor:
University Hospital Brest
Organization:
University Hospital Brest
Study Overview
Official Title:
Assessment of Quitting Versus Using Aspirin Therapy In Patients Treated With Oral Anticoagulation for Atrial Fibrillation or Other Indication With Stabilized Coronary Artery Disease
Status:
RECRUITING
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
AQUATIC
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 andor 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 andor 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 benefitrisk 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
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 andor 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 andor 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 benefitrisk 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
Detailed Description:
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 andor 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 andor 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 benefitrisk 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
AQUATIC is a prospective randomized double-blind placebo controlled parallel-group multi-center study
Randomization into 2 treatment groups and stratified on study center type of OAC VKA vs DOAC antithrombotic treatment received at the time of inclusion dual therapy combining single antiplatelet therapy OAC vs OAC alone
Experimental group Patients intaking full-dose OAC ASA 100mg od
Control group Patients intaking full-dose OAC Placebo of ASA 100mg od
Note
For Apixaban in case of 1 of the followings 80 years old weight 60kg creatinine level 133μmoll Or a creatinine clearance between 30 and 50 mlmin Cockroft Formula the dose of Apixaban will be reduced to 25 mg bid
For Rivaroxaban in case of moderate creatinine clearance Cockroft Formula between 30 and 50 mlmin or severe renal insufficiency between 15 and 29 mlmin the dose of Rivaroxaban will be reduced to 15 mg od
For Dabigatran in case of moderate creatinine clearance Cockroft Formula between 30 and 50 mlmin with age between 75 and 80 years the dose of Dabigatran will be 150 mg bid or 110 mg bid according to the ischemic and hemorrhagic risk of the patient In case of age 80 years andor concomitant administration of Verapamil the dose of Dabigatran will be reduced to 110 mg bid
For VKA target INR International Normalised Ratio between 2 and 3
The primary efficacy objective is to demonstrate in high-risk stabilized patients after PCI requiring also anticoagulation for AF the superiority of the dual therapy ASA 100mg od full-dose of OAC for 24-48 months versus full-dose of OAC alone placebo on a composite endpoint associating cardio-vascular CV mortality myocardial infarction stroke coronary revascularization systemic embolism and acute limb ischemia
The primary safety objective is major bleeding ISTH International Society of Thrombosis and Haemostasis
The secondary efficacy objectives are evaluation of efficacy of dual therapy SA 100mg od OAC full ose versus OAC alone placebo for
The composite of CV mortality MI Myocardial Infarction stroke
CV mortality
All cause death
Myocardial infarction MI
Stent thrombosis definite or probable
Stroke ischemic hemorrhagic or stroke of uncertain cause transient ischemic attack TIA
Coronary revascularization
Systemic embolism
Acute limb ischemia
Net clinical benefit
All cause mortality
Major bleeding define according to the International Society of Thrombosis and Haemostasis ISTH an acute linically overt bleeding accompanied by one or more of the following findings 2gdl decline in Hemoglobin level r 2 red blood cell transfusions over a 24-hour period leeding of a major organ intracranial intramedullary intraocular pericardial interarticular intramuscular and or retro peritoneal or fatal bleeding
Thrombotic cardiovascular events
Myocardial infarction
Stent thrombosis
Stroke ischemic hemorrhagic or stroke of uncertain cause TIA
Any coronary revascularization
Systemic embolism
Acute limb ischemia
The secondary safety objectives are
Major and clinically relevant non major bleeding ISTH
Major bleeding TIMI Thrombolysis In Myocardial Infarction
Major bleeding BARC 3 Bleeding Academic Research Consortium
All the included patients will be randomized at visit 1 and followed every 6 months until death or the end of the study ie achievement of 2-year follow-up of the last included patient maximum of 48 month followup for the first included patientThe first patient may require up to 9 visits
2000 patients are expected to be included
Inclusion period 72 months Duration of patients participation 24 to 48 months depending of time of inclusion
Total study duration 48 months
All included patients will remain in the study until death or the end of the trial ie achievement of 2-year follow-up of the last included patient
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 andor 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 andor 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 benefitrisk 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
AQUATIC is a prospective randomized double-blind placebo controlled parallel-group multi-center study
Randomization into 2 treatment groups and stratified on study center type of OAC VKA vs DOAC antithrombotic treatment received at the time of inclusion dual therapy combining single antiplatelet therapy OAC vs OAC alone
Experimental group Patients intaking full-dose OAC ASA 100mg od
Control group Patients intaking full-dose OAC Placebo of ASA 100mg od
Note
For Apixaban in case of 1 of the followings 80 years old weight 60kg creatinine level 133μmoll Or a creatinine clearance between 30 and 50 mlmin Cockroft Formula the dose of Apixaban will be reduced to 25 mg bid
For Rivaroxaban in case of moderate creatinine clearance Cockroft Formula between 30 and 50 mlmin or severe renal insufficiency between 15 and 29 mlmin the dose of Rivaroxaban will be reduced to 15 mg od
For Dabigatran in case of moderate creatinine clearance Cockroft Formula between 30 and 50 mlmin with age between 75 and 80 years the dose of Dabigatran will be 150 mg bid or 110 mg bid according to the ischemic and hemorrhagic risk of the patient In case of age 80 years andor concomitant administration of Verapamil the dose of Dabigatran will be reduced to 110 mg bid
For VKA target INR International Normalised Ratio between 2 and 3
The primary efficacy objective is to demonstrate in high-risk stabilized patients after PCI requiring also anticoagulation for AF the superiority of the dual therapy ASA 100mg od full-dose of OAC for 24-48 months versus full-dose of OAC alone placebo on a composite endpoint associating cardio-vascular CV mortality myocardial infarction stroke coronary revascularization systemic embolism and acute limb ischemia
The primary safety objective is major bleeding ISTH International Society of Thrombosis and Haemostasis
The secondary efficacy objectives are evaluation of efficacy of dual therapy SA 100mg od OAC full ose versus OAC alone placebo for
The composite of CV mortality MI Myocardial Infarction stroke
CV mortality
All cause death
Myocardial infarction MI
Stent thrombosis definite or probable
Stroke ischemic hemorrhagic or stroke of uncertain cause transient ischemic attack TIA
Coronary revascularization
Systemic embolism
Acute limb ischemia
Net clinical benefit
All cause mortality
Major bleeding define according to the International Society of Thrombosis and Haemostasis ISTH an acute linically overt bleeding accompanied by one or more of the following findings 2gdl decline in Hemoglobin level r 2 red blood cell transfusions over a 24-hour period leeding of a major organ intracranial intramedullary intraocular pericardial interarticular intramuscular and or retro peritoneal or fatal bleeding
Thrombotic cardiovascular events
Myocardial infarction
Stent thrombosis
Stroke ischemic hemorrhagic or stroke of uncertain cause TIA
Any coronary revascularization
Systemic embolism
Acute limb ischemia
The secondary safety objectives are
Major and clinically relevant non major bleeding ISTH
Major bleeding TIMI Thrombolysis In Myocardial Infarction
Major bleeding BARC 3 Bleeding Academic Research Consortium
All the included patients will be randomized at visit 1 and followed every 6 months until death or the end of the study ie achievement of 2-year follow-up of the last included patient maximum of 48 month followup for the first included patientThe first patient may require up to 9 visits
2000 patients are expected to be included
Inclusion period 72 months Duration of patients participation 24 to 48 months depending of time of inclusion
Total study duration 48 months
All included patients will remain in the study until death or the end of the trial ie achievement of 2-year follow-up of the last included patient
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None