E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bleeding among high-risk patients with percutanous coronary intervention with at least one drug-eluting stent |
Reducción del sangrado en pacientes de alto riesgo que se hayan sometido a una intervención coronaria percutánea con por lo menos un stent liberador de fármaco |
|
E.1.1.1 | Medical condition in easily understood language |
Bleeding among high-risk patients with percutanous coronary intervention with at least one drug-eluting stent |
Reducción del sangrado en pacientes de alto riesgo que se hayan sometido a una intervención coronaria percutánea con por lo menos un stent liberador de fármaco |
|
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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065608 |
E.1.2 | Term | Percutaneous coronary intervention |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
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 |
The primary objective of this study is to determine the impact of antiplatelet monotherapy with ticagrelor alone versus Dual Antiplatelet Therapy (DAPT) with ticagrelor plus aspirin for 12 months in reducing clinically relevant bleeding among high-risk patients undergoing PCI who have completed a 3-month course of aspirin plus ticagrelor. |
El objetivo primario de este estudio es determinar el impacto de la monoterapia antiplaquetaria con ticagrelor solo en comparación con DAPT con ticagrelor y aspirina durante 12 meses en la reducción del sangrado clínicamente relevante dentro de los pacientes de alto riesgo que se hayan sometido a PCI exitosas y hayan completado un periodo de 3 meses de DAPT con aspirina y ticagrelor |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to determine the impact of antiplatelet monotherapy with ticagrelor alone versus DAPT with ticagrelor plus aspirin for 12 months in reducing major ischemic adverse events among high-risk patients undergoing PCI who have completed a 3-month course of aspirin plus ticagrelor. |
El objetivo secundario de este estudio es determinar el impacto de la monoterapia antiplaquetaria con ticagrelor solo en comparación con DAPT con ticagrelor y aspirina durante 12 meses en la reducción de los principales eventos adversos isquémicos dentro de los pacientes de alto riesgo que se hayan sometido a PCI exitosas y hayan completado un periodo de 3 meses de DAPT con aspirina y ticagrelor |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Must meet AT LEAST ONE clinical inclusion criterion:
- Adult patients > or = to 65 years of age
- Female gender
- Troponin positive acute coronary syndrome
- Established vascular disease defined as previous MI, documented PAD or CAD/PAD revascularization
- Diabetes mellitus treated with medications or insulin
- Chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 or creatinine clearance (CrCl) <60 ml/min
Must meet AT LEAST ONE angiographic inclusion criterion:
- Multivessel coronary artery disease (CAD)
- Target lesion requiring total stent length >30mm
- Thrombotic target lesion(s)
- Bifurcation lesion(s) with Medina X,1,1 classification requiring at least 2 stents
- Left main (> or = to 50%) or proximal LAD (> or = to70%) lesion
- Calcified target lesion(s) requiring atherectomy |
Requerirá cumplir al menos con un criterio clínico de inclusión:
-Pacientes adultos > o = a 65 años
-Sexo femenino
-Síndrome coronario agudo con troponina positiva
-Enfermedad vascular establecida, previo MI, revascularización PAD o CAD/PAD documentada.
-Diabetes mellitus que requiere medicación
-CKD (eGFR < 60 ml/min/1.73 m2 o CrCl <60 ml/min)
Requerirá cumplir al menos con un criterio angiográfico de inclusión:
-Enfermedad coronaria de múltiples vasos
-Lesión(es) diana que requieren un stent con una longitud total de > 30 mm
-Lesión(es) diana trombótica(s)
-Lesión en la bifurcación (X,1,1) que requiere por lo menos dos stents
-Lesión en la arteria coronaria principal izquierda (> o = a 50%) Lesión en la LAD proximal ( > o = a 70%)
-Lesión(es) diana calcificada que requiere aterectomía |
|
E.4 | Principal exclusion criteria |
Subjects should not enter the study if any of the following exclusion criteria are met:
- Under 18 years of age
- Contraindication to aspirin
- Contraindication to ticagrelor
- Planned surgery within 90 days
- Planned coronary revascularization (surgical or percutaneous) within 90 days
- Need for chronic oral anticoagulation
- Prior stroke
- Dialysis-dependent renal failure
- Active bleeding or extreme-risk for major bleeding (e.g. active peptic ulcer disease, gastrointestinal pathology with a raised risk for bleeding, malignancies with a raised risk for bleeding)
- Salvage PCI or STEMI presentation.
- Liver cirrhosis
- Life expectancy < 1 year
- Unable or unwilling to provide informed consent
- Women of child bearing potential (as determined by hospital standard of care)
- Fibrinolytic therapy within 24 hours of index PCI
- Concomitant therapy with a strong cytochrome P-450 3A inhibitor or inducer
- Platelet count < 100,000 mm3
- Requiring ongoing treatment with aspirin > or = to 325 mg daily |
Los pacientes no podrán incluirse en el estudio si se cumple alguno de los criterios de exclusión:
- Menor de 18 años de edad.
-Contraindicación a la aspirina
-Contraindicación al Ticagrelor
-Cirugía planificada dentro de 90 días.
-Revascularización coronaria planeada (quirúrgica o percutánea) dentro de 90 días
-Necesidad de anticoagulación crónica por vía oral
-Accidente cerebrovascular previo
-Fallo renal con diálisis dependiente
-Sangrado activo o riesgo extremo de sangrado mayor
-PCI de salvamento o presentación STEMI
- Cirrosis hepática
-Expectativa de vida < 1 año
-Imposibilidad o reticencia a firmar el consentimiento informado
-Mujer en edad fértil (Según lo determinado por las normas de partica clínica habitual del hospital)
-Terapia fibrinolítica dentro de las 24 horas del PCI índice
-Terapia concomitante con un inhibidor o inductor del Citocromo p-450 3A
-Recuento plaquetario < 100,000 mm3
-Requerir tratamiento continuo con aspirina > o = a 325 mg diariamente |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary bleeding endpoint of the present study is the time to first occurrence of clinically relevant bleeding, defined as Bleeding Academic Research Consortium (BARC) Types 2, 3 or 5 bleeding.
The primary ischemic endpoint of the present study is the time to first occurrence of confirmed all-cause death, non-fatal myocardial infarction, or stroke. |
El objetivo primario del sangrado es determinar si la monoterapia con ticagrelor es superior a la de ticagrelor y aspirina para el punto de corte del sangrado primario (BARC sangrados tipos 2, 3 o 5).
El objetivo primario de isquemia es determinar si la monoterapia con ticagrelor es superior a la de ticagrelor y aspirina para el punto final de la isquemia primaria (toda causa de muerte, infartos de miocardio no fatales o accidentes cerebrovasculares) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
time from randomisation to death or last follow-up |
Desde el momento de la aleatorización hasta la muerte o ultima visita de seguimiento |
|
E.5.2 | Secondary end point(s) |
Secondary Bleeding Endpoints
Time to first occurrence of:
-Types 3 or 5 bleeding according to definitions from BARC
-Minor or major bleeding according to definitions from Thrombolysis in Myocardial Infarction (TIMI)
-Moderate or severe or life-threatening bleeding according to definitions from GUSTO
-Major bleeding according to definitions from International Society of Thrombosis or Hemostasis (ISTH)
Secondary Ischemic Endpoints
Time to first occurrence of:
-cardiovascular death, non-fatal myocardial infarction, ischemic stroke or clinically-driven revascularization
-cardiovascular death, non-fatal myocardial infarction or ischemic stroke
-definite or probable stent thrombosis
-cardiovascular death
-non-fatal myocardial infarction
-cardiovascular death, non-fatal myocardial infarction or definite or probable stent thrombosis
-ischemic stroke
-all-cause mortality |
Objetivo secundario de sangrado
Primera aparición de:
-Tipos 3 o 5 de sangrado de acuerdo a las definiciones de BARC
-Hemorragia menor o mayor de acuerdo con las definiciones de Trombolisis en Infarto de Miocardio (TIMI)
-Hemorragia moderada o grave o potencialmente mortal de acuerdo con las definiciones de GUSTO
-Hemorragia mayor según las definiciones de la Sociedad Internacional de Trombosis y Hemostasia (ISTH)
Objetivo secundario de isquemia
Primera aparición de:
-Muerte cardiovascular, infarto de miocardio no mortal, accidente cerebrovascular isquémico o revascularización
-Muerte cardiovascular, infarto de miocardio no mortal o accidente cerebrovascular isquémico
-Trombosis del stent definida o probable
-Muerte cardiovascular
-Infarto de miocardio no mortal
-Muerte cardiovascular, infarto de miocardio no fatal o definitivo o probable trombosis del stent
-Ictus isquémico
-Muerte por cualquier causa |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
time from randomisation to death or last follow-up |
Desde el momento de la aleatorización hasta la muerte o ultima visita de seguimiento |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Canada |
Germany |
India |
Israel |
Italy |
Poland |
Spain |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |