| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Prophylaxis of venous thromboembolism |
| Prevención del tromboembolismo venoso |
|
| E.1.1.1 | Medical condition in easily understood language |
| Prevention of blood clots |
| Prevención de coágulos |
|
| 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 |
|
| 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 |
Demostrar la superioridad del tratamiento anticoagulante prolongado
(35 días más un margen de 7 días, es decir, 35-42 días permitidos) con
betrixabán en comparación con el tratamiento habitual (10 ± 4 días) con
enoxaparina para la prevención del TEV en pacientes de riesgo debido a una enfermedad médica aguda. |
|
| E.2.2 | Secondary objectives of the trial |
|
| 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 |
Varón o Mujer (no embarazada, ni en lactancia materna) de 40 años o más en el que se prevea una inmovilización rigurosa de al menos 24 horas en un hospital, después de realizar la aleatorización, y han de presentar uno de los siguientes criterios:
o insuficiencia cardiaca congestiva,
o insuficiencia respiratoria aguda,
o infección aguda sin shock septico,
o trastorno reumático agudo,
o ictus isquémico agudo con hemiparesia o hemiparálisis de las extremidades inferiores |
|
| E.4 | Principal exclusion criteria |
a condition requiring prolonged anticoagulation or anti-platelets
active bleeding or at high risk of bleeding
unable to take oral medication
contraindication to anticoagulant therapy
general conditions in which subjects are not suitable to participate in the study |
Estado que requiera uso prolongado de anticoagulantes o antiplaquetarios
Hemorragia activa o alto riesgo de hemorragia
Incapacidad de tomar la medicación oral
Terapia con anticoagulantes contraindicada |
|
| 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. |
Eficacia
El criterio de valoración principal (combinado) es la aparición de cualquiera de los eventos siguientes hasta la visita del día 35:
TVP proximal asintomática (detectada mediante ecografía), TVP sintomática (proximal o distal), embolia pulmonar (EP) no mortal o muerte relacionada con TEV.
Seguridad:
El criterio de valoración principal de la seguridad será la aparición de hemorragias mayores hasta 7 días después de suspender toda la medicación del estudio. |
|
| 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. |
Un único análisis intermedio de la eficacia y futilidad de los criterios de valoración principal y secundarios cuando aproximadamente el 50 % de los pacientes evaluables en cuanto al criterio de valoración principal cuenten con datos (es decir, 2568 pacientes con un criterio de valoración principal evaluable).
Los criterios de valoración de la eficacia y seguridad serán analizados por el CIVD cuando finalicen el seguimiento de:
? 250 pacientes
? 750 pacientes
? 1500 pacientes
? 3000 pacientes
? 4500 pacientes
? Cuando 2568 pacientes cuenten con datos evaluables sobre el criterio de valoración principal. Esto podrá suceder simultáneamente con una de las reuniones mencionadas anteriormente en caso de que coincida con los criterios de reunión |
|
| 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 |
Eficacia:
El criterio de valoración secundario (combinado) es la aparición de cualquiera de los eventos siguientes hasta el final del periodo de tratamiento parenteral:
Aparición de TVP proximal asintomática (detectada por ultrasonidos), TVP sintomática (proximal o distal), EP no mortal o muerte relacionada con TEV.
Otros criterios de valoración secundarios de la eficacia:
Los siguientes criterios de valoración combinados se analizarán:
? TEV sintomático: la aparición de TEV hasta la visita del día 35 (muerte relacionada con TEV, EP no mortal o TVP sintomática).
? Aparición de TVP proximal asintomática, TVP sintomática (proximal o distal), EP no mortal o todas las causas de muerte hasta la visita del día 35.
Seguridad:
Criterios de valoración secundarios de la seguridad:
? Aparición de hemorragias no importantes pero clínicamente relevantes (hemorragias NICR) hasta 7 días después de la suspensión de toda la medicación del estudio.
? Aparición de hemorragias importantes hasta el momento de suspensión de la medicación parenteral del estudio.
? Aparición de hemorragias NICR hasta el momento de suspensión de la medicación parenteral del estudio.
? Aparición de hemorragias importantes entre el momento de suspensión de la medicación parenteral del estudio y el día 35.
? Aparición de hemorragias NICR entre el momento de suspensión de la medicación parenteral del estudio y el día 35.
? Aparición de hemorragias importantes hasta el momento de suspensión de la medicación parenteral del estudio en los pacientes con insuficiencia renal grave (aclaramiento de creatinina < 30 ml/min).
? Aparición de hemorragias NICR hasta el momento de suspensión de la medicación parenteral del estudio en los pacientes con insuficiencia renal grave.
? Aparición de hemorragias importantes hasta 7 días después de la suspensión de toda la medicación del estudio en los pacientes con insuficiencia renal grave.
? Aparición de hemorragias NICR hasta 7 días después de la suspensión de toda la medicación del estudio en los pacientes con insuficiencia renal grave.
? Aparición de ictus, según lo adjudicado por el CEC |
|
| 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. |
Un único análisis intermedio de la eficacia y futilidad de los criterios de valoración principal y secundarios cuando aproximadamente el 50 % de los pacientes evaluables en cuanto al criterio de valoración principal cuenten con datos (es decir, 2568 pacientes con un criterio de valoración principal evaluable).
Los criterios de valoración de la eficacia y seguridad serán analizados por el CIVD cuando finalicen el seguimiento de:
? 250 pacientes
? 750 pacientes
? 1500 pacientes
? 3000 pacientes
? 4500 pacientes
? Cuando 2568 pacientes cuenten con datos evaluables sobre el criterio de valoración principal. Esto podrá suceder simultáneamente con una de las reuniones mencionadas anteriormente en caso de que coincida con los criterios de reunión |
|
| 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 |
| Doble enmascarado |
| Double dummy |
|
| 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 | 13 |
| 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 |
| Austria |
| Belgium |
| Brazil |
| Bulgaria |
| Canada |
| Chile |
| Croatia |
| Czech Republic |
| Denmark |
| Estonia |
| France |
| Germany |
| Hong Kong |
| Hungary |
| India |
| Israel |
| Italy |
| Korea, Republic of |
| Latvia |
| Lithuania |
| Mexico |
| Peru |
| Poland |
| Romania |
| Russian Federation |
| Singapore |
| South Africa |
| Spain |
| Ukraine |
| United Kingdom |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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