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

Primary Purpose

Acute Coronary Syndrome, Atrial Fibrillation, Coronary Artery Disease

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Dual Therapy
Triple Therapy
Sponsored by
LMU Klinikum
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Coronary Syndrome focused on measuring ACS, Triple-Therapy, AF, oral anticoagulation (OAC), non-vitamin-K oral anticoagulant (NOAC)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Munich University Hospital
  • Universitätsklinikum der RWTH Aachen
  • Charité, Campus Benjamin Franklin
  • Charité, Campus Virchow-Klinikum
  • Klinikum Coburg
  • Westdeutsches Herzzentrum am Universitätsklinikum
  • Universitätsmedizin Greifswald
  • Universitätsmedizin Göttingen
  • Universitätsklinikum Heidelberg
  • UKHS Campus Kiel
  • Klinikum Lüdenscheid
  • Universitätsmedizin Mainz
  • Universitätsklinikum Mannheim
  • Klinikum Augustinum
  • Städtisches Klinikum München-Neuperlach
  • Universitätsmedizin Rostock

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Dual therapy (incl. NOAC)

Triple therapy (incl. VKA)

Arm Description

Apixaban plus Clopidogrel

Phrenprocoumon plus Clopidogrel plus ASA

Outcomes

Primary Outcome Measures

The combined endpoint of moderate or major bleeding complications during the initial hospitalization and follow up (Bleeding Academic Research Consortium (BARC) type ≥ 2 bleeding)

Secondary Outcome Measures

Combined event of death, myocardial infarction, definite stent thrombosis, stroke/other systemic thromboembolism and all the individual components of the composite secondary endpoint
Bleeding complications (Major bleeding: BARC > 3b bleeding)

Full Information

First Posted
May 24, 2016
Last Updated
August 12, 2020
Sponsor
LMU Klinikum
Collaborators
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), Technical University of Munich, Helmholtz Zentrum München, University of Göttingen, University of München, University Medicine Greifswald
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1. Study Identification

Unique Protocol Identification Number
NCT02789917
Brief Title
APixaban vs. PhenpRocoumon in Patients With ACS and AF: APPROACH-ACS-AF
Acronym
APPROACH
Official Title
APixaban Versus PhenpRocoumon: Oral AntiCoagulation Plus Antiplatelet tHerapy in Patients With Acute Coronary Syndrome and Atrial Fibrillation
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
June 2016 (undefined)
Primary Completion Date
August 2020 (Actual)
Study Completion Date
August 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
LMU Klinikum
Collaborators
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), Technical University of Munich, Helmholtz Zentrum München, University of Göttingen, University of München, University Medicine Greifswald

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Coronary Syndrome, Atrial Fibrillation, Coronary Artery Disease
Keywords
ACS, Triple-Therapy, AF, oral anticoagulation (OAC), non-vitamin-K oral anticoagulant (NOAC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
403 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dual therapy (incl. NOAC)
Arm Type
Experimental
Arm Description
Apixaban plus Clopidogrel
Arm Title
Triple therapy (incl. VKA)
Arm Type
Active Comparator
Arm Description
Phrenprocoumon plus Clopidogrel plus ASA
Intervention Type
Other
Intervention Name(s)
Dual Therapy
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Triple Therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
The combined endpoint of moderate or major bleeding complications during the initial hospitalization and follow up (Bleeding Academic Research Consortium (BARC) type ≥ 2 bleeding)
Time Frame
up to 6 months after randomization
Secondary Outcome Measure Information:
Title
Combined event of death, myocardial infarction, definite stent thrombosis, stroke/other systemic thromboembolism and all the individual components of the composite secondary endpoint
Time Frame
up to 6 months after randomization
Title
Bleeding complications (Major bleeding: BARC > 3b bleeding)
Time Frame
up to 6 months after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Reza Wakili, MD
Organizational Affiliation
Klinikum der Universität München (LMU)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Steffen Massberg, Prof.
Organizational Affiliation
Klinikum der Universität München (LMU)
Official's Role
Study Chair
Facility Information:
Facility Name
Munich University Hospital
City
Munich
State/Province
Bavaria
ZIP/Postal Code
81377
Country
Germany
Facility Name
Universitätsklinikum der RWTH Aachen
City
Aachen
Country
Germany
Facility Name
Charité, Campus Benjamin Franklin
City
Berlin
Country
Germany
Facility Name
Charité, Campus Virchow-Klinikum
City
Berlin
Country
Germany
Facility Name
Klinikum Coburg
City
Coburg
Country
Germany
Facility Name
Westdeutsches Herzzentrum am Universitätsklinikum
City
Essen
Country
Germany
Facility Name
Universitätsmedizin Greifswald
City
Greifswald
Country
Germany
Facility Name
Universitätsmedizin Göttingen
City
Göttingen
Country
Germany
Facility Name
Universitätsklinikum Heidelberg
City
Heidelberg
Country
Germany
Facility Name
UKHS Campus Kiel
City
Kiel
Country
Germany
Facility Name
Klinikum Lüdenscheid
City
Lüdenscheid
Country
Germany
Facility Name
Universitätsmedizin Mainz
City
Mainz
Country
Germany
Facility Name
Universitätsklinikum Mannheim
City
Mannheim
Country
Germany
Facility Name
Klinikum Augustinum
City
München
Country
Germany
Facility Name
Städtisches Klinikum München-Neuperlach
City
München
Country
Germany
Facility Name
Universitätsmedizin Rostock
City
Rostock
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Inclusion in central DZHK Database (German Centre for Cardiovascular Research)

Learn more about this trial

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

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