Multi-national Study Investigating the Effect and Safety of rFXIII on Transfusion Needs in Patients Undergoing Heart Surgery

Study Overview
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Brief Summary
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This trial is conducted in Canada, Asia, Europe and USA. The aim of this clinical trial is to investigate the effect and safety of rFXIII on transfusion needs in patients undergoing heart surgery.

Official Title
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A Multi-Centre, Randomised, Double-Blind, Placebo Controlled Trial on Efficacy and Safety of FXIII Replenishment With Two Different Doses of Recombinant Factor XIII Following Cardiopulmonary Bypass Surgery

Conditions
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Acquired Bleeding Disorder, Cardiac Surgery Requiring Cardiopulmonary Bypass

Intervention / Treatment
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* Drug: catridecacog
* Drug: catridecacog
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Planned coronary artery bypass grafting (CABG) or CABG plus single heart valve replacement/repair or planned replacement/repair of a single heart valve Exclusion Criteria: Known intolerance to protamine Known or suspected allergy to the used antifibrinolytic agent Refusal to receive blood or blood product Planned surgery including the aortic arch and/or descending aorta Planned surgery including any implantable ventricular assist device Adult congenital heart diseases Two or more previous cardiac surgery procedures Any known autoimmune diseases: Collagen vascular disease (Systemic lupus erythematosus, Rheumatoid arthritis, Sjögrens syndrome) - Endocrine: hyperthyroidism (Graves disease), adrenal insufficiency, Hashimoto's thyroiditis - Neurologic: Multiple sclerosis, myasthenia gravis - Skin: pemphigous vulgaris Hematologic: Pernicious anaemia, Autoimmune haemolytic anaemia - Vasculitis - Primary or secondary antiphospholipid syndrome Weight above 140 kg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FXIII17.5IU/Kg<br>Recombinant factor XIII at a single dose of 17.5 IU/kg lean body mass (LBM) was administered via slow i.v. push at a rate not exceeding two mL per minute. | Drug: catridecacog<br>* Single dose via slow intravenous (i.v.) push at a rate not exceeding two mL per minute<br>|
| Experimental: FXIII35IU/Kg<br>Recombinant factor XIII at a single dose of 35 IU/kg lean body mass (LBM) was administered via slow i.v. push at a rate not exceeding two mL per minute. | Drug: catridecacog<br>* Single dose via slow intravenous (i.v.) push at a rate not exceeding two mL per minute<br>|
| Placebo Comparator: Placebo<br>Recombinant factor XIII placebo was administered as a single dose via slow i.v. push at a rate not exceeding two mL per minute. | Drug: placebo<br>* Single dose via slow intravenous (i.v.) push at a rate not exceeding two mL per minute<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Avoiding Any Allogeneic Transfusions for Seven Days Post-operative or Until Discharge, Whichever Came First | Proportion of patients avoiding blood products given via allogeneic transfusion. Blood products were defined as any of the following: RBC, platelets, FFP, fibrinogen concentrate and clotting factor(s) concentrate, including cryoprecipitate. | measured ongoing from dosing until day 7 or discharge, whichever came first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Thromboembolic Events | Percentage of subjects with thromboembolic events (AMI, cerebrovascular thromboembolic event, peripheral artery occlusion, DVT, pulmonary embolism) until end of trial | measured from screening until 5-7 weeks post Trial Drug Administration | 
| Percentage of Subjects With rFXIII Antibody Reaction | Immunogenicity as number of subjects who manifested FXIII antibody reaction until end of trial. The percentage may be derived from the number of subjects treated with rFXIII with available antibody measurement at visit 8. | measured from screening until 5-7 weeks post Trial Drug Administration | 
| Percentage of Subjects With Critical Adverse Events | Percentage of subjects with critical adverse events (thromboembolic events (AMI, cerebrovascular thromboembolic event, peripheral artery occlusion, DVT, pulmonary embolism), renal dysfunction, re-operation and death) until end of trial | measured from screening until 5-7 weeks post Trial Drug Administration | 
| Percentage of Subjects With Serious Adverse Events | Percentage of subjects with serious adverse events until end of trial. | measured from screening until 5-7 weeks post Trial Drug Administration |