E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of stroke or systemic embolism in atrial fibrillation |
Prevenção do AVC e do embolismo sistémico na fibrilhação auricular |
|
E.1.1.1 | Medical condition in easily understood language |
Prevention of stroke (caused by blocked blood supply to a part of brain) and blood clots travelling through the blood stream to plug another vessel in people with irregular and often rapid heartbeat |
Prevenção do AVC e de coágulos sanguíneos que viajam através da corrente sanguínea bloqueando outros vasos, em pessoas com batimento cardíaco irregular e muitas vezes rápido |
|
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 | 10049165 |
E.1.2 | Term | Cerebrovascular accident prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049910 |
E.1.2 | Term | Thromboembolism prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To demonstrate that asundexian is superior (at least non-inferior) when compared with apixaban for prevention of stroke and systemic embolism in participants with atrial fibrillation at risk for stroke - To demonstrate that asundexian is superior to apixaban as assessed by International Society on Thrombosis and Hemostasis (ISTH) major bleeding in participants with atrial fibrillation at risk for stroke - To demonstrate that asundexian is superior to apixaban with respect to benefit and risk |
-Demonstrar que o asundexiano é superior (pelo menos não inferior) quando comparado com o apixabano para a prevenção do AVC e do embolismo sistémico nos participantes com fibrilhação auricular em risco de AVC -Demonstrar que o asundexiano é superior ao apixabano, conforme avaliado por hemorragia major da Sociedade Internacional de Trombose e Hemostase (International Society on Thrombosis and Hemostasis - ISTH) nos participantes com fibrilhação auricular em risco de AVC -Demonstrar que o asundexiano é superior ao apixabano no que diz respeito ao benefício e ao risco |
|
E.2.2 | Secondary objectives of the trial |
- To compare the effects of asundexian and apixaban with respect to composite and individual efficacy endpoints - To compare asundexian and apixaban with respect to composite and individual bleeding endpoints - To compare the benefit and risk of asundexian and apixaban with respect to a composite of efficacy and safety endpoints |
- Comparar os efeitos do asundexiano e do apixabano no que diz respeito a parâmetros de avaliação compostos e individuais de eficácia - Comparar o asundexiano e o apixabano no que diz respeito aos parâmetros de avaliação compostos e individuais de hemorragia - Comparar o benefício e o risco do asundexiano e do apixabano no que diz respeito a parâmetros de avaliação compostos de eficácia e segurança
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 18 years of age or older (at legal age of consent according to local legislation) at the time of signing the informed consent 2. Atrial fibrillation documented by ECG evidence with an indication for indefinite treatment with an oral anticoagulant 3. CHA2DS2-VASc score ≥ 3 if male or ≥ 4 if female, OR CHA2DS2-VASc score of 2 if male or 3 if female and enrichment criteria. |
1. 18 anos de idade ou mais (na idade legal de consentimento de acordo com a legislação local) no momento da assinatura do consentimento informado 2. Fibrilhação auricular documentada por evidências de ECG com indicação para tratamento por tempo indeterminado com anticoagulante oral 3. Pontuação CHA2DS2-VASc ≥ 3 no caso do sexo masculino ou ≥ 4 no caso do sexo feminino, OU Pontuação CHA2DS2-VASc de 2 no caso do sexo masculino ou 3 no caso do sexo feminino e critérios de enriquecimento
|
|
E.4 | Principal exclusion criteria |
1. Mechanical heart valve prosthesis 2. Moderate-to-severe mitral stenosis at the time of inclusion into the study 3. Atrial fibrillation only due to reversible cause 4. Requirement for chronic anticoagulation for a different indication than atrial fibrillation |
1. Prótese valvular mecânica cardíaca 2. Estenose mitral moderada a grave no momento da inclusão no ensaio 3. Fibrilhação auricular apenas devido a causa reversível 4. Requisito de anticoagulação crónica para uma indicação diferente da fibrilhação auricular |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Time to first occurrence of composite of stroke or systemic embolism 2. Time to first occurrence of ISTH major bleeding 3. Time to first occurrence of composite of stroke, systemic embolism, or ISTH major bleeding |
1. Tempo até à primeira ocorrência do Composto de AVC ou embolismo sistémico 2. Tempo até à primeira ocorrência da hemorragia major da ISTH 3. Tempo até à primeira ocorrência do Composto de AVC, embolismo sistémico ou hemorragia major da ISTH |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 34 months |
Até 34 meses |
|
E.5.2 | Secondary end point(s) |
1. Time to first occurrence of composite of ischemic stroke or systemic embolism 2. Time to first occurrence of all-cause mortality 3. Time to first occurrence of ischemic stroke 4. Time to first occurrence of cardiovascular (CV) death 5. Time to first occurrence of composite of CV death, stroke, or myocardial infarction 6. Time to first occurrence of composite of ISTH major or clinically relevant non-major bleeding 7. Time to first occurrence of clinically relevant non-major bleeding 8. Time to first occurrence of hemorrhagic stroke 9. Time to first occurrence of intracranial hemorrhage 10. Time to first occurrence of fatal bleeding 11. Time to first occurrence of minor bleeding 12. Time to first occurrence of composite of stroke, systemic embolism, ISTH major bleeding, or all-cause mortality 13. Time to first occurrence of composite of disabling stroke (modified Rankin Scale (mRS) ≥ 3), critical bleeding, or all-cause mortality
|
1. Tempo até à primeira ocorrência do composto de AVC isquémico ou embolismo sistémico 2. Tempo até à primeira ocorrência de mortalidade por todas as causas 3. Tempo até à primeira ocorrência de AVC isquémico 4. Tempo até à primeira ocorrência de morte de causa cardiovascular (CV) 5. Tempo até à primeira ocorrência do Composto de morte de causa CV, AVC ou enfarte do miocárdio 6. Tempo até à primeira ocorrência do Composto de hemorragia major da ISTH e não major clinicamente relevante 7. Tempo até à primeira ocorrência de hemorragia não major clinicamente relevante 8. Tempo até à primeira ocorrência de AVC hemorrágico 9. Tempo até à primeira ocorrência de hemorragia intracraniana 10. Tempo até à primeira ocorrência de hemorragia fatal 11. Tempo até à primeira ocorrência de hemorragia minor 12. Tempo até à primeira ocorrência do Composto de AVC, embolismo sistémico, hemorragia major da ISTH ou mortalidade por todas as causas 13. Tempo até à primeira ocorrência do composto de AVC incapacitante (mRS ≥ 3), hemorragia crítica ou mortalidade por todas as causas |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 34 months |
Até 34 meses |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Dupla simulação |
Double dummy |
|
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 | Yes |
E.8.2.3.1 | Comparator description |
|
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 | 19 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 494 |
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 |
Argentina |
Australia |
Brazil |
Canada |
China |
Colombia |
Israel |
Japan |
Korea, Republic of |
Malaysia |
Singapore |
Taiwan |
United States |
Austria |
Estonia |
Finland |
France |
Latvia |
Lithuania |
Poland |
Sweden |
Bulgaria |
Netherlands |
Romania |
Spain |
Switzerland |
Czechia |
Germany |
Greece |
Italy |
Belgium |
Denmark |
Hungary |
Norway |
Portugal |
Slovakia |
Turkey |
United Kingdom |
|
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
|
Last visit of the last subject |
Última consulta do último participante |
|
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 | 5 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |