E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Reversal of vitamin K antagonist (VKA) induced anticoagulation in patients needing urgent surgery associated with significant bleeding risk. |
Reversión de anticoagulación inducida con antagonistas de la vitamina K (AVK) en pacientes que precisan cirugía urgente, en quienes se asocia un riesgo significativo de hemorragia. |
|
E.1.1.1 | Medical condition in easily understood language |
Reversal of vitamin K antagonist (VKA) induced anticoagulation in patients needing urgent surgery associated with significant bleeding risk. |
Reversión de anticoagulación inducida con antagonistas de la vitamina K (AVK) en pacientes que precisan cirugía urgente, en quienes se asocia un riesgo significativo de hemorragia. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10065667 |
E.1.2 | Term | Haemorrhage 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 |
The primary objective of the study is to demonstrate that the efficacy of OCTAPLEX as a reversal agent in patients under VKA therapy with the need for urgent surgery with significant bleeding risk is clinically non-inferior to Beriplex® P/N (Kcentra). |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to investigate the safety and tolerability of OCTAPLEX compared to Beriplex® P/N (Kcentra) in patients under VKA therapy with the need for urgent surgery with significant bleeding risk. |
El objetivo principal del estudio es demostrar que la eficacia de OCTAPLEX como agente reversor en pacientes tratados con AVK que precisan cirugía urgente y presentan riesgo significativo de hemorragia es clínicamente no inferior a la de Beriplex® P/N (Kcentra). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients at least 18 years of age. 2. Patients currently on oral anticoagulation treatment with VKA of coumadin or warfarin type. 3. Patients being admitted to the hospital or currently hospitalized where: • an urgent surgery carrying significant bleeding risk (≥50 mL expected blood loss) is required as part of routine clinical care; • the use of oral or parenteral vitamin K alone to reverse anticoagulation is deemed too slow or inappropriate for reversal; 4. Patients with an INR of 2.0 or above at the time of decision to reverse the anticoagulation status. 5. Patients who have given written informed consent and who are able and willing to comply with the procedures laid out in the study protocol. |
1. Pacientes varones o mujeres, de edad igual o superior a 18 años. 2. Pacientes actualmente en tratamiento anticoagulante oral con AVK de coumadin o tipo warfarina. 3. Pacientes que ingresan en el hospital o actualmente ingresados: • que como parte de su atención clínica de rutina precisan una cirugía urgente, con riesgo significativo de hemorragia (pérdida hemática esperada ≥50 ml); • en los que el uso de vitamina K oral o parenteral sola, para revertir la anticoagulación, se considera demasiado lento o inadecuado para dicha reversión; 4. Pacientes cuya ratio normalizada internacional (RNI) es de 2,0 o superior en el momento de decidir la reversión del estado de anticoagulación. 5. Pacientes que han dado su consentimiento informado por escrito, con capacidad y voluntad de cumplir los procedimientos descritos en el Protocolo del Estudio. |
|
E.4 | Principal exclusion criteria |
1. Patients with a life expectancy of less than 48 hours per physician’s judgment (e.g., patients with a Glasgow Coma Scale equal to 3 or a head Abbreviated Injury Score of 6, patients requiring continuous inotropic or pressor support, and patients whose status is post cardiac arrest). 2. Patients for whom the planned surgery or procedure is commonly associated with a very low bleeding risk (e.g., catheter placement, gastroscopy). 3. Patients with a history of TEEs, myocardial infarction (MI), unstable angina pectoris, critical aortic stenosis, cerebrovascular accident, TIA, severe peripheral vascular disease, or disseminated intravascular coagulation within 3 months of enrollment. 4. Patients with a known congenital bleeding disorder. 5. Patients with a known antiphospholipid antibody syndrome. 6. Patients with present or past specific factor inhibitor activity. 7. Patients with thrombocytopenia of <80,000/μL or history of heparin-induced thrombocytopenia. 8. Patients who have received heparin of any type or any non-VKA anticoagulant within 24 hours prior to enrollment into the study or with potential need to receive these medications before completion of hemostasis evaluation at the end of surgery. 9. Patients who have received PCCs, FFP or vitamin K within 72 hours prior to enrollment into the study. 10. Patients with a known history of hypersensitivity to plasma-derived products. 11. Patients with acute major bleeding or polytrauma. 12. Pregnant or nursing women. 13. Patients participating in another interventional clinical study currently or during the past 30 day prior to enrollment into this study. 14. Patients previously enrolled in this study. |
1. Pacientes con una expectativa de vida inferior a 48 horas, a criterio médico (ej. pacientes con una Escala de Coma de Glasgow igual a 3 o una Puntuación Abreviada de Lesión en la Cabeza de 6, pacientes que precisan soporte vasopresor o inotrópico continuo y pacientes post-parada cardiaca). 2. Pacientes en quienes la cirugía o el procedimiento planificado se asocia habitualmente a muy bajo riesgo de hemorragia (ej. colocación de catéter, gastroscopia). 3. Pacientes con antecedentes de eventos tromboembólicos (ETEs), infarto de miocardio, angina de pecho inestable, estenosis aórtica crítica, accidente cerebrovascular, ataque isquémico transitorio, enfermedad vascular periférica severa o coagulación intravascular diseminada, en los 3 meses posteriores a su entrada en el estudio. 4. Pacientes con trastornos hemorrágicos congénitos conocidos. 5. Pacientes con síndrome de anticuerpo antifosfolípido conocido. 6. Pacientes con actividad presente o pasada de inhibidor de factor específico. 7. Pacientes con trombocitopenia <80.000/μl o antecedentes de trombocitopenia inducida por heparina. 8. Pacientes que han recibido heparina de cualquier tipo o cualquier anticoagulante no AVK en las 24 horas previas a la entrada en el estudio o con potencial necesidad de recibir estas medicaciones antes de finalizar la evaluación de la hemostasia al finalizar la cirugía. 9. Pacientes que han recibido concentrados de complejo de protrombina (CCPs), plasma fresco congelado o vitamina K en las 72 horas antes de la entrada en el estudio. 10. Pacientes con antecedentes conocidos de hipersensibilidad a productos derivados plasmáticos. 11. Pacientes con importante hemorragia aguda o politrauma. 12. Mujeres gestantes o que amamantan. 13. Pacientes que participan actualmente en otro estudio clínico intervencional o que hayan participado en los 30 días previos a la entrada en este estudio. 14. Pacientes previamente incluidos en este estudio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the hemostatic efficacy rating at the end of the surgery. |
El criterio de valoración principal de la eficacia es la puntuación de la eficacia hemostásica al final de la cirugía. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of surgery. |
Final de la cirugía. |
|
E.5.2 | Secondary end point(s) |
• Proportion of patients with an INR value of less than or equal to 1.5 at 30 min (± 15 min) after the end of infusion. • Change in coagulation factor levels from baseline to 30 (± 15 min) after the end of infusion: o Factor FII o Factor FVII o Factor FIX o Factor FX • Proportion of patients receiving red blood cells (RBC) during the surgery |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Proportion of patients with an INR value of less than or equal to 1.5 at 30 min (± 15 min) after the end of infusion. • Change in coagulation factor levels from baseline to 30 (± 15 min) after the end of infusion: o Factor FII o Factor FVII o Factor FIX o Factor FX • Proportion of patients receiving red blood cells (RBC) during the surgery |
• Proporción de pacientes con un valor RNI igual o inferior a 1,5 a los 30 (± 15) minutos tras el fin de la infusión. • Cambio en niveles de factores de coagulación respecto al valor basal hasta 30 (± 15) minutos tras el fin de la infusión: o Factor FII o Factor FVII o Factor FIX o Factor FX • Proporción de pacientes que reciben glóbulos rojos (hematíes) durante la cirugía |
|
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 | 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) | 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 | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
Bulgaria |
Germany |
Poland |
Romania |
Russian Federation |
Spain |
Ukraine |
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
|
LVLS |
Última visita del último paciente. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 |