| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with acute coronary syndrome and atrial fibrillation |
| Patienten mit akutem Koronarsyndrom und Vorhofflimmern |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with acute coronary syndrome and atrial fibrillation |
| Patienten mit akutem Koronarsyndrom und Vorhofflimmern |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10003658 |
| E.1.2 | Term | Atrial fibrillation |
| E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10051592 |
| E.1.2 | Term | Acute coronary syndrome |
| E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate an optimal antithrombotic treatment strategy with the best benefit-to-risk ratio with primary endpoint bleeding comparing a dual antithrombotic regimen including clopidogrel plus the FXa inhibitor apixaban versus a guideline conform triple treatment strategy including a vitamin K antagonist plus ASA plus clopidogrel in a predefined high risk population in the context of an ACS (after successful PCI) and the concomitant diagnosis of AF with need for an oral anticoagulation. We postulate that a dual antithrombotic regimen (clopidogrel plus the FXa inhibitor apixaban) is superior to the triple treatment strategy (vitamin K antagonist plus ASA plus clopidogrel) regarding reduction of bleeding events. |
| n. a. |
|
| E.2.2 | Secondary objectives of the trial |
| Assessment of efficacy of the assigned therapy in regard to prevent thrombotic coronary events by the antiplatelet therapy and systemic thrombotic events by oral anticoagulation. |
| n. a. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects will only be included in the study if they meet all of the following 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.
|
Patienten werden nur in die Studie eingeschlossen, wenn sie alle der folgenden Kriterien erfüllen:
- Unterschriebene Einverständniserklärung
- Patienten mit akutem Koronarsyndrom und erfolgreicher perkutaner Koronarintervention
- Indikation zur oralen Antikoagulation aufgrund von nicht-valvulärem Vorhofflimmern oder Vorhofflattern (CHA2DS2VASc score ≥ 2)
- Männer und Frauen ≥ 18 Jahre
- Gebärfähige Frauen müssen einen negativen Serum- oder Urin-Schwangerschaftstest innerhalb von 24h vor Start der Studienmedikation vorweisen (minimale Sensitivität 25 IU/L oder äquivalente Einheiten von HCG).
- Frauen dürfen nicht stillen.
- Gebärfähige Frauen müssen einverstanden sein, den Kontrazeptionsvorgaben für die Dauer der Therapie mit den Studienmedikamenten und 30 Tagen danach (Dauer eines Ovulationszyklus) zu folgen.
|
|
| E.4 | Principal exclusion criteria |
Subjects will not be included in the study if any of the following criteria applies:
• 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
|
Patienten dürfen nicht in die Studie eingeschlossen werden, wenn eines der folgenden Kriterien zutrifft:
- Alter < 18 Jahre
- Aktive Blutung
- Anamnese intrakranieller Blutungen
- Anamnese einer TIMI Majorblutung oder einer BARC ≥3b Blutung in den letzten 6 Monaten
- Anamnese eines Magengeschwürs in den letzten 6 Monaten
- Anamnese eines komplizierten oder prolongierten kardiogenen Schocks in den letzten 2 Wochen vor Randomisierung. Ein komplizierter oder prolongierter kardiogener Schock wird definiert als ein kardiogener Schock, der eine mechanische Beatmung oder die Unterstützung von positiv inotropen Substanzen (z.B. Katecholaminen) für ≥7 Tage notwendig gemacht hat.
- Geplante große chirugische Maßnahme während der Studiendauer mit geplanter Pausierung der antithrombozytären Therapie
- Lebenserwartung unter einem Jahr bzw. schwere Erkrankung (z.B. maligner Art)
- Mechanischer Herzklappenersatz
- Valvuläres Vorhofflimmern
- Schwere Niereninsuffizienz (Kreatinin Clearance < 30ml/min)
- Schwere Leberinsuffizienz (Child-Pugh C) oder erhöhte Transaminasen über die doppelte obere Norm
- Fehlende Aufklärungsfähigkeit des Patienten
- Bekannter Abusus von Medikamenten, Drogen oder Alkohol
- Probanden mit bekannten Kontraindikationen zu Apixaban, Clopidogrel oder ASS
- Relevante Blutbildveränderungen: Plättchenzahl < 50 G/L oder > 600 G/L
- Aktive oder geplante Schwangerschaft, aktives oder geplantes Stillen, Frauen bis 90 Tage nach Entbindung. Gebärfähige Frauen, die eine medizinisch zuverlässige Kontrazeptions-methode für die gesamte Studiendauer ablehnen (z. B. oral, als Injektion oder mittels intrauterinen Implantaten), außer sie sind chirurgisch sterilisiert oder hysterektomiert oder aufgrund anderer Ursache nicht gebärfähig.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Bleeding events according to BARC criteria type ≥2 |
| n. a. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| until 6 months after randomisation |
| n. a. |
|
| E.5.2 | Secondary end point(s) |
1) Composite clinical efficacy outcome: all-cause death, myocardial infarction, definite stent thrombosis, stroke/other systemic thromboembolism
2) Net clinical outcome: all-cause death, myocardial infarction, definite stent thrombosis, stroke/other systemic thromboembolism or BARC > 3b bleeding)
3) individual components of the composite secondary endpoint
4) cardiovascular death
5) any bleeding episodes (according to Thrombolysis in Myocardial Infarction (TIMI) and BARC criteria)
|
| n. a. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| To determine differences within all the other interesting secondary endpoints of the study between control versus the experimental arm of the study patients will be followed the entire six months study timeframe. |
| n. a. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
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