E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acquired Deficiency of Prothrombin Complex Coagulation Factors (II, VII, IX, X) due to oral anticoagulant therapy with Vitamin K antagonists |
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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 | 10037045 |
E.1.2 | Term | Prothrombin deficiency |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 |
•To evaluate the efficacy of Prothromplex Total in the reversal of effects of oral anticoagulant therapy with respect to normalisation of increased international normalised ratio (INR) |
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E.2.2 | Secondary objectives of the trial |
•To collect information on the shortening of prothrombin time (PT)
•To assess in-vivo recovery of clotting factors II, VII, IX and X at 30 (±5) minutes post administration of Prothromplex Total
•To assess safety of Prothromplex Total when administered to patients with acquired coagulopathy due to treatment with oral anticoagulants, with respect to clinically observed adverse drug reactions and coagulation markers
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Subject is at least 18 years of age at enrolment with acquired prothrombin complex coagulation factor (II, VII, IX, X) deficiency, due to oral anticoagulation with vitamin K antagonists (e.g. coumarin, warfarin), requiring reversal of oral anticoagulation for urgent surgery, invasive procedure or acute bleeding episode
•Subject has provided written informed consent
•Subject has INR ≥ 2.0 at screening
•Subject must have been on stable doses of anticoagulant or has a known history of stable INR for at least 72 hours prior to screening
•Subject is willing and able to comply with the requirements of the protocol
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E.4 | Principal exclusion criteria |
•Subject has laboratory and/or clinical symptoms which are clearly indicative of disseminated intravascular coagulation (DIC)
•Subject has been treated with whole blood, fresh frozen plasma (FFP), or platelets within 6 hours prior to study enrolment
•Subject has a hypersensitivity to PCC constituents (including heparin-induced thrombocytopenia)
•Subject has blood loss of ≥ 5 units of blood
•Subject has known congenital Protein C, Protein S, or Antithrombin deficiency, or hereditary bleeding disorder
•Subject has a life expectancy of < 3 months
•Subject has been on oral anticoagulant treatment for a period of < 4 weeks for the treatment of a thrombotic event such as deep vein thrombosis or pulmonary embolism
•Subject has an acute ischaemic cardiovascular disorder
•Subject has or is suspected to have sepsis
•Subject with acute or chronic liver failure (hepatic cirrhosis Child-PUGH score C)
•Subject has renal failure undergoing dialysis
•Subject has participated in another clinical study involving an IP or device within 30 days prior to study enrolment or is scheduled to participate in another clinical study involving an IP or device during the course of this study
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects who achieve normalisation of INR to ≤ 1,3 within 30 (±5) minutes post administration of Prothromplex Total |
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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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |