E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Reduction of blood loss in subjects exposed to CPB during cardiac surgery at high risk for bleeding |
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MedDRA Classification |
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 is to evaluate the relative efficacy of ecallantide and tranexamic acid in the reduction of blood loss in subjects undergoing cardiac surgery including the use of CPB, associated with a high risk of bleeding. |
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E.2.2 | Secondary objectives of the trial |
• To assess the safety of ecallantide in subjects undergoing cardiac surgery including the use of CPB, associated with a high risk of bleeding; • To explore clinical outcomes that may correlate with blood loss in subjects undergoing cardiac surgery including the use of CPB, associated with a high risk of bleeding.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent (by study subject) prior to any study-related procedure not part of normal medical care; 2. Male or female between the ages of 18 and 85 years old, inclusive; and 3. Planned cardiac surgery using cardio-pulmonary bypass, for one of the following procedures; • Any repeat sternotomy • surgery to repair or replace more than one valve • Combined CABG plus repair or replacement of at least one valve 4. If female, subject is non-lactating, and is either: • Not of childbearing potential, defined as postmenopausal for at least one year or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or historectomy; • Of childbearing potential but is not pregnant as confirmed by negative pregnancy test at time of screening (based on the β-subunit of HCG), and is practicing the barrier method of birth control along with one of the following methods: oral or parenteral contraceptives for three months prior to study drug administration, a vasectomized partner, or abstinence from sexual intercourse.
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E.4 | Principal exclusion criteria |
1. Planned primary CABG, single valve repair or replacement surgery, or any off pump procedure; 2. Body weight <55 kg; 3. Planned hypothermia (<28ºC); 4. Planned transfusion in the peri-operative or post-operative periods; 5. Planned transfusion of pre-operatively donated autologous blood; 6. Female subjects who are pregnant or lactating; 7. Planned use of desmopressin, lysine analogs (other than study medication), atrial natriuretic hormone or recombinant activated Factor VII; 8. Planned use of corticosteroids in the pump prime solution; 9. Ejection fraction <30% within 90 days prior to surgery; 10. Evidence of a myocardial infarction within 5 days prior to surgery; 11. History of stroke or transient ischemic attack within 3 months prior to surgery; 12. Hypotension or heart failure requiring the use of inotropes or mechanical devices within 24 hours prior to surgery; 13. Serum creatinine >2.0 mg/dL within 48 hours prior to surgery; 14. Serum hepatic enzymes (aspartate aminotransferase or alanine aminotransferase) above 2.5 times the upper limit of normal for the applicable laboratory; 15. Hematocrit <32% within 48 hours prior to surgery; 16. Platelet count below the normal range for the applicable laboratory within 14 days prior to surgery; 17. History of, or family history of, bleeding or clotting disorder (e.g. von Willebrand’s Disease, idiopathic thrombocytopenia purpura) or thrombophilia such as anti-thrombin III deficiency or Factor V Leiden mutation; 18. History of heparin-induced thrombocytopenia; 19. Prothrombin time (PT) and/or activated partial thromboplastin time (aPTT) >1.5 X normal range unless subject received heparin within 24 hours of test; 20. Serious intercurrent illness or active infection (e.g. endocarditis, sepsis, active malignancy requiring treatment); 21. Any previous exposure to ecallantide; 22. Receipt of an investigational drug or device 30 days prior to participation in the current study; 23. Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the subject or would preclude the subject from successful completion of the study; 24. Inability to comply with the protocol for the duration of the study; 25. Known allergy to any agent expected to be used in the intra-operative or post-operative periods; and 26. Administration of: a. Eptifibatide within 6 hours prior to surgery b. Tirofiban hydrochloride within 6 hours prior to surgery c. *Enoxaparin sodium or other low-molecular-weight heparin <24 hours prior to surgery d. Prasugrel within 10 days prior to surgery e. Clopidogrel within 3 days prior to surgery f. Ticlopidine within 7 days prior to surgery g. Abciximab within 5 days prior to surgery h. *Bivalirudin, argatroban or lepirudin within 6 hours prior to surgery i. *Fondaparinux within 72 hours prior to surgery j. Chlorpromazine within 7 days prior to surgery *Prophylactic use permitted for the prevention of deep vein thrombosis. 27. Planned use of heparin bonded bypass circuits; 28. Known allergy or hypersensitivity to tranexamic acid or any of the other ingredients; 29. Disturbance of color sense; 30. Evidence of hematuria or any acute thromboses or thromboembolic diseases such as deep vein thrombosis, pulmonary embolism, or vertebral vein thrombosis.
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E.5 End points |
E.5.1 | Primary end point(s) |
The key variables of interest include the following:
• Volume of packed red blood cells administered from the start of surgery up to 12 hours after the end of surgery; • Volume of packed red blood cells administered at each of the following timepoints: during surgery, within 24 hours after the end of surgery and at discharge; • Volume of blood products (platelets and FFP) and related products (albumin) administered during surgery and within 12 and 24 hours after the end of surgery and at discharge; • Administration of blood or blood products at each of the following timepoints; during surgery, within 12 hours after the end of surgery, within 24 hours after the end of surgery and at discharge; • Cumulative volume of chest tube drainage from insertion until 12 and until 24 hours after the end of surgery; • Change in serum creatinine over the duration of the study; and • MI (adjudicated)
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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 | 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) | 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 | 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.8.3 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
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 | 0 |
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 | 0 |
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 |