APixaban vs. PhenpRocoumon in Patients With ACS and AF: APPROACH-ACS-AF

Coronary Artery Disease Clinical Trial

— APPROACH  

Official title:

APixaban Versus PhenpRocoumon: Oral AntiCoagulation Plus Antiplatelet tHerapy in Patients With Acute Coronary Syndrome and Atrial Fibrillation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02789917
• Other study ID #: GE IDE MucT003-16
• Status: Completed
• Phase: Phase 4
• Start date: June 2016
• Est. completion date: August 2020

Study information

• Verified date: August 2020
• Source: Klinikum der Universitaet Muenchen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

It is hypothesised that a dual therapy strategy by oral anticoagulation with the new Factor-Xa-inhibitor apixaban plus clopidogrel is superior to a triple therapy regimen with phenprocoumon plus acetylsalicylic acid (ASA) and clopidogrel with respect to avoiding bleeding events in patients with atrial fibrillation undergoing percutaneous coronary intervention in the setting of an acute coronary syndrome.

Description:

Patients with atrial fibrillation (AF) presenting an acute coronary syndrome (ACS) and undergoing PCI require a triple therapy with a combination of oral anticoagulation (OAC) and dual anti-platelet therapy. Current guidelines recommend a regimen consisting of aspirin, clopidogrel and an oral anticoagulant. Although effective in preventing recurrent ischemia, triple therapy confers an elevated bleeding risk, which also has a major impact on the patients' prognosis and survival. Data from one randomized trial suggest that omitting aspirin in patients with indication for triple therapy may reduce the risk of bleeding without an increase of the rate of ischemic events. In addition, the recently introduced non-vitamin-K oral anticoagulants (NOACs) show less bleeding events as compared to vitamin-K antagonist in AF patients. In this trial it is postulated that a dual therapy consisting of the factor-Xa inhibitor apixaban and clopidogrel is associated with significant lower bleeding rates as compared to traditional triple therapy with aspirin, clopidogrel and a vitamin K antagonist (VKA). To test this hypothesis, patients with atrial fibrillation, who underwent PCI in the setting of an ACS will be randomized to either a dual therapy (apixaban+clopidogrel) or a triple therapy (aspirin+clopiodgrel+VKA). The patients will be followed-up for 6 months after randomization.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 403
• Est. completion date: August 2020
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed written informed consent

• Patients with an ACS after successful percutaneous coronary intervention

• Indication for oral anticoagulation due to non-valvular atrial fibrillation or atrial flutter (CHA2DS2VASc score = 2)

• Males and Females, ages = 18

• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.

• Women must not be breastfeeding

• WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs plus 30 days (duration of ovulatory cycle) post-treatment completion. However they must still undergo pregnancy testing.

Exclusion Criteria:

• Age < 18 years

• History of intracranial bleeding

• Active bleeding

• History of TIMI major bleeding according to TIMI and/or type =3b BARC criteria in the last 6 months

• History of peptic ulcer in the last 6 months

• Subjects with a history of a complicated or prolonged cardiogenic shock in the last two weeks prior to randomization. A complicated or prolonged cardiogenic shock is defined by a cardiogenic shock that required mechanical ventilation or the cardiovascular support with positive inotropic drugs (i.v. catecholamine) for =7 days

• Planned major surgery during the study course with planned discontinuation of antithrombotic therapy

• Expected life expectancy of less than a year and/or severe illness (e.g. malignancy)

• Mechanical valve replacement

• Valvular atrial fibrillation

• Severe renal insufficiency (creatinine clearance < 30ml/min)

• Severe liver insufficiency (Child-Pugh-class C) or elevated hepatic transaminases >2 times the upper limit of normal

• Patient's inability to fully comply with the study protocol

• Known or persistent abuse of medication, drugs or alcohol reliable by the investigator in individual cases

• Subjects with known contraindications to apixaban, phenprocoumon, clopidogrel or ASA treatment, which are hypersensitive to the drug substance or any component of the product

• Relevant hematologic deviations: platelet count < 50 G/L or platelet count > 600 G/L

• Current or planned pregnancy or nursing women, women 90 days after childbirth. Females of childbearing potential, who do not use and are not willing to use medically reliable methods of contraception for the entire study duration (such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices) unless they are surgically sterilized / hysterectomized or there are any other criteria considered sufficiently

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Atrial Fibrillation
• Coronary Artery Disease
• Syndrome

Intervention

Other:
• Dual Therapy
Combination of Apixaban 5mg/dl (or in reduced dosing of 2.5 mg/d depending on age, renal function and body weight) in combination with Clopidogrel 75 mg/d for 6 months.
• Triple Therapy
HAS-BLED-Score <3: Combination of Phrenprocoumon (INR 2.0-2.5), Clopidogrel (75mg/d) and ASA (100 mg/d) for 6 months. HAS-BLED-Score = 3: Combination of Phrenprocoumon (INR 2.0-2.5), Clopidogrel (75mg/d) and ASA (100 mg/d) for 1 month followed by Phrenprocoumon (INR 2.0-3.0) and Clopidogrel (75mg/d) for 5 months.

Locations

Country	Name	City	State
Germany	Universitätsklinikum der RWTH Aachen	Aachen
Germany	Charité, Campus Benjamin Franklin	Berlin
Germany	Charité, Campus Virchow-Klinikum	Berlin
Germany	Klinikum Coburg	Coburg
Germany	Westdeutsches Herzzentrum am Universitätsklinikum	Essen
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Universitätsmedizin Greifswald	Greifswald
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	UKHS Campus Kiel	Kiel
Germany	Klinikum Lüdenscheid	Lüdenscheid
Germany	Universitätsmedizin Mainz	Mainz
Germany	Universitätsklinikum Mannheim	Mannheim
Germany	Klinikum Augustinum	München
Germany	Städtisches Klinikum München-Neuperlach	München
Germany	Munich University Hospital	Munich	Bavaria
Germany	Universitätsmedizin Rostock	Rostock

Sponsors (7)

Lead Sponsor	Collaborator
Klinikum der Universitaet Muenchen	Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), Helmholtz Zentrum München, Technische Universität München, University Medicine Greifswald, University of Göttingen, University of München

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The combined endpoint of moderate or major bleeding complications during the initial hospitalization and follow up (Bleeding Academic Research Consortium (BARC) type = 2 bleeding)		up to 6 months after randomization
Secondary	Combined event of death, myocardial infarction, definite stent thrombosis, stroke/other systemic thromboembolism and all the individual components of the composite secondary endpoint		up to 6 months after randomization
Secondary	Bleeding complications (Major bleeding: BARC > 3b bleeding)		up to 6 months after randomization