E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
venous thromboembolism |
tromboembolismo venoso |
|
E.1.1.1 | Medical condition in easily understood language |
venous thromboembolism |
tromboembolismo venoso |
|
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 | LLT |
E.1.2 | Classification code | 10066899 |
E.1.2 | Term | Venous thromboembolism |
E.1.2 | System Organ Class | 100000004866 |
|
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 |
Occurrence of confirmed composite endpoint of asymptomatic deep venous thrombosis (DVT), confirmed symptomatic venous thromboembolic events (VTE), fatal pulmonary embolism (PE) or unexplained death. |
El objetivo principal de este estudio es evaluar si al menos una dosis de MAA868 no es inferior a la de enoxaparina 40 mg hasta el día 14 después de la aleatorización en cuanto a incidencia de ATV totales evaluados en pacientes que se someten a una ATR unilateral. En caso de no inferioridad (NI), se evaluará la superioridad |
|
E.2.2 | Secondary objectives of the trial |
- Occurrence of confirmed composite endpoint of major bleeding and clinically relevant non-major (CRNM) bleeding events. - Occurrence of confirmed composite endpoint of asymptomatic deep vein thrombosis (DVT), confirmed symptomatic venous thromboembolic events (VTE), fatal pulmonary embolism (PE) or unexplained death. |
Objetivo 1: evaluar el efecto de MAA868 relativo a enoxaparina en cuanto a incidencia de hemorragias mayores y no mayores clínicamente relevantes (NMCR) (definición de la International Society on Thrombosis and Haemostasis (ISTH)) hasta el día 14 y hasta el día 50 después de la aleatorización. Objetivo 2: evaluar si al menos una dosis de MAA868 no es inferior a la de enoxaparina 40 mg hasta el día 50 después de la aleatorización y en la visita de fin de estudio (EOS) en cuanto a incidencia de ATV totales evaluados en pacientes que se someten a una ATR unilateral. En caso de no inferioridad, se evaluará la superioridad. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Scheduled to undergo elective unilateral total knee arthroplayts (TKA). - Willing to comply with study requirements including bilateral venography at Day 12 ± 2 days. - Body weight between 50 kg and 130 kg inclusive. - Normal aPTT, PT, INR at screening. - See full list in protocol. |
-Pacientes de ambos sexos (>/= 18 y < 80 años de edad). -Programados para someterse a una ATR unilateral electiva. -Debe obtenerse el consentimiento informado por escrito. -Dispuestos a cumplir los requisitos de estudio que incluyen la venografía bilateral el día 12 ± 2 días. -Peso corporal entre 50 y 130 kg (ambos incluidos). -TTPA, TP e INR normales en la selección. - Ver la lista completa en el protocolo. |
|
E.4 | Principal exclusion criteria |
- History of arterial or venous thromboembolism; - abnormally extended primary or secondary bleeding after trauma or intervention, stroke, transient ischemic attack or traumatic or non-traumatic intracranial bleed; - bleeding disorder; - MI or unstable angina pectoris within 12 months of the screening; - Uncontrolled hypertension (SBP/DBP ≥ 150/95 mmHg at the screening). - Medications that increase the risk of bleeding, including antiplatelet (such as aspirin), anticoagulant and fibrinolytic agents; - eGFR <60 mL/min/1.73m2; - Poorly controlled diabetes (HbA1C >10%); - Liver dysfunction (ALT/AST >3 xULN or TBL >2 x ULN); - BMI ≥ 40 kg/m2. - See full list in protocol. |
-Indicación formal de tratamiento anticoagulante de dosis complete o tratamiento antiplaquetario doble (TAPD). -Antecedentes de tromboembolismo venoso profundo. -Diátesis hemorrágica. -Antecedentes familiares de trastorno hemorrágico. -Lesiones GI activas o sospecha de lesiones GI con predisposición a causar acontecimientos hemorrágicos. -Antecedentes de accidente cerebrovascular, accidente isquémico transitorio o hemorragia intracraneal o intraocular, traumática o no traumática. -Cirugía mayor o traumatismo durante los últimos 6 meses. -Medicamentos que incrementen el riesgo de hemorragia, como anticoagulantes, fármacos fibrinolíticos y TAPD; el tratamiento antiplaquetario simple no está prohibido. -Los pacientes a quienes se haya dejado insertado un catéter intratecal después de la cirugía para el manejo del dolor en la cohorte B. -Inestabilidad hemodinámica en las 2 horas posteriores a la cirugía en la cohorte B. -Hemoglobina < 13 g/dl en hombres y < 12 g/dl en mujeres o antecedentes de transfusiones de sangre durante el mes anterior a la selección. -TFGe < 60 ml/min/1,73 m2). - Ver la lista completa en el protocolo. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Number of patients with confirmed composite endpoint. |
Número de pacientes con presencia de una variable compuesta confirmada |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Number of patients with composite venous thromboembolic events (VTE). |
Número de pacientes con acontecimientos trombóticos venosos (ATV). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- day 1 to day 50 and day 1 to day 110 |
-De día 1 a día 50 y de día 1 a día 110. |
|
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 | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Randomized, open-label study with blinded endpoint adjudication |
|
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 | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Austria |
Belgium |
Chile |
Czech Republic |
Estonia |
Germany |
Hungary |
Israel |
Italy |
Latvia |
Lebanon |
Lithuania |
Malaysia |
Mexico |
Russian Federation |
South Africa |
Spain |
Turkey |
|
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
|
LVLS |
última visita último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 16 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |