E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylaxis of venous thromboembolism. |
Profilassi del tromboembolismo venoso |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of blood clots |
Prevenzione della formazione di coaguli di sangue. |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
E.1.2 | Term | Venous thromboembolism prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
Demonstrate the superiority of extended duration (35 days + 7 day window, i.e. 35-42 days allowed) anticoagulation with betrixaban as compared to the standard of care (10 ± 4 days) with enoxaparin for prevention of VTE in patients who are at risk due to acute medical illness. |
Dimostrare la superiorita' dell’anticoagulazione di durata estesa (35 giorni + finestra di 7 giorni, ossia sono ammessi 35-42 giorni) con betrixaban rispetto allo standard di cura (10 ± 4 giorni) con enoxaparina nella prevenzione del TEV in pazienti a rischio a causa di patologia medica acuta. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female (non-pregnant, non-breastfeeding women) ages 40 years and older anticipated to be severely immobilized for at least 24 hours after randomization hospitalized with one of the following: o congestive heart failure, o acute respiratory failure, o acute infection without septic shock, o acute rheumatic disorders, o acute ischemic stroke with lower extremity hemiparesis or hemiparalysis. |
Uomini o donne (non in gravidanza o allattamento) di eta' superiore o uguale ai 40 anni, avvisati che saranno fortemente immobilizzati per almeno 24 ore dopo la randomizzazione, ospedalizzati per una delle seguenti condizioni: o Insufficienza cardiaca; o Insufficienza respiratoria acuta; o Infezione acuta senza shock settico; o Disturbi reumatici acuti; o Ictus ischemico acuto con emiparesi degli arti inferiori o emi-paralisi. |
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E.4 | Principal exclusion criteria |
o A condition requiring prolonged anticoagulation or anti-platelets; o Active bleeding or at high risk of bleeding; o Unable to take oral medication; o ontraindication to anticoagulant therapy; o General conditions in which subjects are not suitable to participate in the study. |
o Condizioni che richiedono prolungata terapia anticoagulante o antipiastrinica. o Sanguinamento attivo o rischio di sanguinamento. o Incapacita' di assumere farmaci per via orale. o Controindicazioni alla terapia anticoagulante. o Condizioni generali per le quali il soggetto non e' in grado di partecipare allo studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: The primary (composite) outcome is the occurrence of any of the following events through the Day 35 visit: Asymptomatic proximal DVT (as detected by ultrasound), symptomatic DVT (proximal or distal), non-fatal PE, or VTE related death Safety: The primary safety outcome will be the occurrence of major bleeding through 7 days after discontinuation of all study medication. |
EFFICACIA L’outcome primario (composito) e' l’occorrenza di uno qualsiasi dei seguenti eventi fino alla visita del Giorno 35: TVP prossimale asintomatica (rilevata con ecografia), TVP sintomatica (prossimale o distale), EP non fatale o decesso legato a TEV. SICUREZZA L’outcome di sicurezza primario sara' l’occorrenza di sanguinamento maggiore fino a 7 giorni dopo l’interruzione di tutti i farmaci dello studio. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
There will be a single interim efficacy and futility analysis of the primary and secondary outcomes when approximately 50% of the primary-endpoint evaluable patients have data (i.e., 2568 patients with an evaluable primary outcome). Efficacy and safety outcomes will be reviewed by the IDMC at the following defined intervals: • After 250 patients have completed follow-up • After 750 patients have completed follow-up • After 1500 patients have completed follow-up • After 3000 patients have completed follow-up • After 4500 patients have completed follow-up • After 2568 patients have evaluable primary outcome data. This may occur simultaneously with one of the above meetings if the meeting criteria coincide. |
Sara' effettuata una sola analisi ad interim di efficacia e futilita' degli outcome primari e secondari quando sara' disponibile circa il 50% dei pazienti valutabili per l’endpoint primario (vale a dire 2568 pazienti con un outcome primario valutabile). Gli outcome di efficacia e sicurezza saranno esaminati dal IDMC ai seguenti intervalli definiti: -Dopo che 250 pazienti avranno completato il follow-up (f-up),-Dopo che 750 pazienti avranno completato il f-up, -Dopo che 1500 pazienti avranno completato il f-up, -Dopo che 3000 pazienti avranno completato il f-up, -Dopo che 4500 pazienti avranno completato il f-up, -Dopo che 2568 pazienti disporranno di dati per l’outcome primario valutabile. Cio' potra' anche verificarsi in contemporanea ad uno dei sopra menzionati incontri. |
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E.5.2 | Secondary end point(s) |
Efficacy: The key secondary (composite) outcome is the occurrence of any of the following events through the end of the parenteral treatment period: Asymptomatic proximal DVT (as detected by ultrasound), symptomatic DVT (proximal or distal), non-fatal PE, or VTE related death Other Secondary Efficacy Outcomes: The following other secondary composite outcomes will be examined: • Symptomatic VTE: The occurrence of symptomatic VTE through the Day 35 visit (VTE-related death, nonfatal PE or symptomatic DVT). • The occurrence of asymptomatic proximal DVT, symptomatic DVT (proximal or distal), non-fatal PE, or allcause mortality through the Day 35 visit. Safety: Secondary safety outcomes include the following: • Occurrence of clinically relevant non-major bleeding (CRNM bleeding) through 7 days after discontinuation of all study medication. • Occurrence of major bleeding through the time of parenteral study medication discontinuation. • Occurrence of CRNM bleeding through the time of parenteral study medication discontinuation. • Occurrence of major bleeding from the time of parenteral study medication discontinuation through Day 35. • Occurrence of CRNM bleeding from the time of parenteral study medication discontinuation through Day 35. • Occurrence of major bleeding through the time of parenteral study medication discontinuation in patientswith severe renal insufficiency (creatinine clearance < 30 ml/min). • Occurrence of CRNM bleeding through the time of parenteral study medication discontinuation in patients with severe renal insufficiency. • Occurrence of major bleeding through 7 days after discontinuation of all study medication in patients with severe renal insufficiency. • Occurrence of CRNM bleeding through 7 days after discontinuation of all study medication in patients with severe renal insufficiency. • Occurrence of stroke, as adjudicated by the CEC. |
EFFICACIA L’outcome chiave secondario (composito) e' l’occorrenza di uno qualsiasi dei seguenti eventi fino alla fine del trattamento parenterale: TVP prossimale asintomatica (rilevata con ecografia), TVP sintomatica (prossimale o distale), EP non fatale o decesso legato a TEV. Altri parametri secondari di efficacia: • TEV sintomatico: L’occorrenza di TEV sintomatico fino alla visita del Giorno 35 (decesso legato a TEV, EP non fatale o TVP sintomatica) • L’occorrenza di TVP prossimale asintomatica, TVP sintomatica (prossimale o distale), EP non fatale o mortalita' per tutte le cause fino alla visita del Giorno 35 SICUREZZA • L’occorrenza di sanguinamento non maggiore clinicamente rilevante (sanguinamento CRNM) fino a 7 giorni dopo l’interruzione di tutti i farmaci dello studio • Occorrenza di sanguinamento maggiore fino al momento dell’interruzione del farmaco dello studio per via parenterale • Occorrenza di sanguinamento CRNM fino al momento dell’interruzione del farmaco dello studio per via parenterale • Occorrenza di sanguinamento maggiore dal momento dell’interruzione del farmaco dello studio per via parenterale fino al Giorno 35 • Occorrenza di sanguinamento CRNM dal momento dell’interruzione del farmaco dello studio per via parenterale fino al Giorno 35 • Occorrenza di sanguinamento maggiore fino al momento dell’interruzione del farmaco dello studio per via parenterale in pazienti con insufficienza renale grave (clearance della creatinina < 30 ml/min) • Occorrenza di sanguinamento CRNM fino al momento dell’interruzione del farmaco dello studio per via parenterale in pazienti con insufficienza renale grave • Occorrenza di sanguinamento maggiore fino a 7 giorni dopo l’interruzione di tutti i farmaci dello studio in pazienti con insufficienza renale grave • Occorrenza di sanguinamento CRNM fino a 7 giorni dopo l’interruzione di tutti i farmaci dello studio in pazienti con insufficienza renale grave • Occorrenza di ictus, stabilito dal CEC. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
There will be a single interim efficacy and futility analysis of the primary and secondary outcomes when approximately 50% of the primary-endpoint evaluable patients have data (i.e., 2568 patients with an evaluable primary outcome). Efficacy and safety outcomes will be reviewed by the IDMC at the following defined intervals: • After 250 patients have completed follow-up • After 750 patients have completed follow-up • After 1500 patients have completed follow-up • After 3000 patients have completed follow-up • After 4500 patients have completed follow-up • After 2568 patients have evaluable primary outcome data. This may occur simultaneously with one of the above meetings if the meeting criteria coincide. |
Sara' effettuata una sola analisi ad interim di efficacia e futilita' degli outcome primari e secondari quando sara' disponibile circa il 50% dei pazienti valutabili per l’endpoint primario (vale a dire 2568 pazienti con un outcome primario valutabile). Gli outcome di efficacia e sicurezza saranno esaminati dall’IDMC ai seguenti intervalli definiti: -Dopo che 250 pazienti avranno completato il follow-up (f-up),-Dopo che 750 pazienti avranno completato il f-up, -Dopo che 1500 pazienti avranno completato il f-up, -Dopo che 3000 pazienti avranno completato il f-up, -Dopo che 4500 pazienti avranno completato il f-up, -Dopo che 2568 pazienti disporranno di dati per l’outcome primario valutabile. Cio' potra' anche verificarsi in contemporanea ad uno dei sopra menzionati incontri. |
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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 | Yes |
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) | 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 |
doppio mascheramento |
double dummy |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 136 |
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 |
Chile |
Croatia |
Hong Kong |
India |
Israel |
Korea, Republic of |
Mexico |
Peru |
Russian Federation |
Singapore |
South Africa |
Ukraine |
United States |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 22 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 26 |
E.8.9.2 | In all countries concerned by the trial days | 0 |