Detail Article

Informations générales (source: ClinicalTrials.gov)

Numéro NCT

NCT04217447 En recrutement IDF

Titre

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

Type

Interventional

Pathologie

Fibrillation auriculaire
Maladie des artères coronaires
Maladie coronarienne
Ischémie myocardique

Phase

Phase 3

Promoteur

University Hospital, Brest (Voir sur ClinicalTrials)

Date de début

mai 2020

Date de fin

mai 2028

Dernière mise à jour

29 juin 2024

Résumé

- 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.

Détail

Voir le détail - 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. 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 > 133μmol/l; Or a creatinine clearance between 30 and 50 ml/min (Cockroft Formula), the dose of Apixaban will be reduced to 2.5 mg bid. - For Rivaroxaban: in case of moderate creatinine clearance (Cockroft Formula) (between 30 and 50 ml/min) or severe renal insufficiency (between 15 and 29 ml/min) 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 ml/min) 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 and/or 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: 2g/dl 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 (i.e. achievement of 2-year follow-up of the last included patient, maximum of 48 month followup for the first included patient).The first patient may require up to 9 visits . 2000 patients are expected to be included. Inclusion period : 72 months. Duration of patient's 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 (i.e. achievement of 2-year follow-up of the last included patient). Fermer le détail

Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
HOPITAL NOVO	DECALF	Active, sans recrutement	04/12/2024 13:04:44	Contacter
Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
AP-HP - Hôpital Bichat	Grégory DUCROCQ, PUPH	En recrutement IDF		Contact (sur clinicalTrials)
AP-HP - Hôpital Henri Mondor-Albert Chenevier	Romain GALLET, PU	En recrutement IDF		Contact (sur clinicalTrials)
AP-HP - Hôpital Saint Antoine	Franck BOCCARA, PUPH	En recrutement IDF		Contact (sur clinicalTrials)
CENTRE HOSPITALIER SUD FRANCILIEN	Pascal GOUBE	En recrutement IDF		Contact (sur clinicalTrials)
CH DE VERSAILLES SITE ANDRE MIGNOT	Jean Louis GEORGES, PU	En recrutement IDF		Contact (sur clinicalTrials)
GHI LE RAINCY MONTFERMEIL		Annulé		Contact (sur clinicalTrials)
HOPITAL PRIVE D ANTONY	Patrick DUPOUY, PU	En recrutement IDF		Contact (sur clinicalTrials)
Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
CH d'Annecy-Genevois - 74370 - Annecy - France	Loic BELLE, PU	En recrutement		Contact (sur clinicalTrials)
CH d'Arras - 62000 - Arras - France	Damien BROUCQSAULT, PU	En recrutement		Contact (sur clinicalTrials)
CH de la Côte Basque - Bayonne - 64100 - Bayonne - France	Jean Noel LABEQUE, PU	En recrutement		Contact (sur clinicalTrials)
CH de Lens - 62300 - Lens - France	Hugo VERHEYDE, PU	En recrutement		Contact (sur clinicalTrials)
CH de Pau - 64000 - Pau - France	Nicolas DELARCHE, PU	En recrutement		Contact (sur clinicalTrials)
CH Louis Pasteur - Chartres - Le Coudray - 28630 - Chartres - France	Grégoire RANGE, PU	En recrutement		Contact (sur clinicalTrials)
CH Pierre Nouveau -Cannes - 06414 - Cannes - France	Gilles ZEMOUR, PU	En recrutement		Contact (sur clinicalTrials)
CH St Joseph-St Luc Lyon - 69007 - Lyon - France	Olivier DUBREUIL, PU	En recrutement		Contact (sur clinicalTrials)
CHR d'Orléans - 45067 - Orléans - France	Marc GORALSKI, PU	En recrutement		Contact (sur clinicalTrials)
CHRU d'Amiens - 80054 - Amiens - France	Laurent LEBORGNE, PUPH	En recrutement		Contact (sur clinicalTrials)
CHRU de Tours - 37170 - Tours - France	Denis ANGOULVANT, PUPH	En recrutement		Contact (sur clinicalTrials)
CHU d'Angers - 49933 - Angers - France	Alain FURBER, PU	En recrutement		Contact (sur clinicalTrials)
CHU de Clermont-Ferrand - 63000 - Clermont-Ferrand - France	Pascal MOTREFF, PUPH	En recrutement		Contact (sur clinicalTrials)
CHU de Limoges - 87042 - Limoges - France	Victor ABOYANS, PUPH	En recrutement		Contact (sur clinicalTrials)
CHU de Rennes - 35033 - Rennes - France	Hervé LEBRETON, PUPH	En recrutement		Contact (sur clinicalTrials)
CHU de Strasbourg - 67091 - Strasbourg - France	Patrick OHLMANN, PUPH	En recrutement		Contact (sur clinicalTrials)
Clinique du Millénaire - Montpellier - 34000 - Montpellier - France	Christophe PIOT, PUPH	En recrutement		Contact (sur clinicalTrials)
Clinique Pasteur-Toulouse - 31076 - Toulouse - France	Antoine SAUGUET, PU	En recrutement		Contact (sur clinicalTrials)
Clinique Rhena - Strasbourg - 67000 - Strasbourg - France	Nicolas LHOEST, PU	En recrutement		Contact (sur clinicalTrials)
Clinique St Clothilde -La Réunion - 97400 - La Réunion - France	Lucas MORLON, PU	En recrutement		Contact (sur clinicalTrials)
Clinique St Hilaire - Rouen - 76000 - Rouen - France	Matthieu GODIN, PU	En recrutement		Contact (sur clinicalTrials)
Hôpital Haut Lévêque -CHU Bordeaux-Pessac - 33604 - Bordeaux - France	Pierre COSTE, PUPH	En recrutement		Contact (sur clinicalTrials)
Hôpital Louis Pradel - Bron - 69677 - Bron - France	François DERIMAY, PU	En recrutement		Contact (sur clinicalTrials)
Marseille-Hôpital Nord - 13015 - Marseille - France	Laurent BONELLO, PUPH	En recrutement		Contact (sur clinicalTrials)
Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
CH Chalon sur Saône - 71100 - Chalon-sur-Saône - France	Maxime FAYARD, PU	En recrutement		Contact (sur clinicalTrials)
CH Compiègne - 60200 - Compiègne - France	Jérôme CLERC, PU	En recrutement		Contact (sur clinicalTrials)
CH d'Antibes - 06606 - Antibes - France	Anne BELLEMAIN-APPAIX, PU	En recrutement		Contact (sur clinicalTrials)
CH d'Avignon - 84902 - Avignon - France	Michel PANSIERI, PU	En recrutement		Contact (sur clinicalTrials)
CH de Seclin - 59113 - Seclin - France	Alessandro COSENZA, PU	En recrutement		Contact (sur clinicalTrials)
CH Haguenau - 67504 - Haguenau - France	Sabrina UHRY, PU	Recrutement non commencé		Contact (sur clinicalTrials)
CH Martigues - Martigues - France	Serge YVORRA, PU	En recrutement		Contact (sur clinicalTrials)
CH Périgueux - 24000 - Périgueux - France	Sandrine GOUGNOT, PU	En recrutement		Contact (sur clinicalTrials)
CHR de Metz - 57085 - Metz - France		Annulé		Contact (sur clinicalTrials)
CHRU de Lille - 59037 - Lille - France	Gilles LEMESLE, PUPH	En recrutement		Contact (sur clinicalTrials)
CHU de Brest - 29609 - Brest - France	Romain DIDIER, PH	En recrutement		Contact (sur clinicalTrials)
CHU de Dijon - 21000 - Dijon - France	Yves COTTIN, PUPH	En recrutement		Contact (sur clinicalTrials)
CHU de Grenoble - 38043 - Grenoble - France	Gerald VANZETTO, PUPH	En recrutement		Contact (sur clinicalTrials)
CHU de Montpellier - 24298 - Montpellier - France	Florence LECLERCQ, PUPH	En recrutement		Contact (sur clinicalTrials)
CHU de Nancy - Hôpitaux de Brabois - 54500 - Vandœuvre-lès-Nancy - France	Batric POPOVIC, PU	En recrutement		Contact (sur clinicalTrials)
CHU de Nîmes - 30000 - Nîmes - France	Guillaume CAYLA, PUPH	En recrutement		Contact (sur clinicalTrials)
CHU de Poitiers - 86021 - Poitiers - France	Claire BOULETI, PUPH	En recrutement		Contact (sur clinicalTrials)
CHU de Rouen - 76031 - Rouen - France	Eric DURAND, PUPH	En recrutement		Contact (sur clinicalTrials)
CHU de Toulouse - 31059 - Toulouse - France	Thibault LHERMUSIER, PU	En recrutement		Contact (sur clinicalTrials)
Clinique Les Fontaines - Melun - 77000 - Melun - France	Eduardo APTECAR, PU	En recrutement		Contact (sur clinicalTrials)
GHM - Grenoble - 38028 - Grenoble - France	Damien GUIJARRO, PU	En recrutement		Contact (sur clinicalTrials)
Marseille- Hôpital La Timone - 13385 - Marseille - France	Thomas CUISSET, PUPH	En recrutement		Contact (sur clinicalTrials)
Paris-HEGP Cardiologie - 75015 - Paris - France	Etienne PUYMIRAT, PU	En recrutement		Contact (sur clinicalTrials)
Paris-HEGP Médecine vasculaire - 75015 - Paris - France	Emmanuel MESSAS, PUPH	En recrutement		Contact (sur clinicalTrials)
Paris-Lariboisière - 75010 - Paris - France	Jean-Guillaume DILLINGER, PU	En recrutement		Contact (sur clinicalTrials)
Paris-Pitié-Salpêtrière - 75013 - Paris - France	Mathieu KERNEIS, PU	En recrutement		Contact (sur clinicalTrials)

Critères

Genre

Tous

Nombre d'inclusion

Critère d'inclusion

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) or other
indication 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 >6
months.

2. History of PCI (>6 months) 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

Critère de non inclusion

- Any coronary event within 6 months 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

NCT04217447 - Assessment of Quitting Versus Using Aspirin Therapy In Patients Treated With Oral Anticoagulation for Atrial Fibrillation or Other Indication With Stabilized Coronary Artery Disease (AQUATIC)

Informations générales
Etablissements
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