Enhancement of the Haemostatic Effect of Platelets in the Presence of High Normal Concentrations of Von Willebrand Factor

Study Overview
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Brief Summary
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Assessment of high-normal dosage of Wilate ® compared to placebo administered in combination with platelets to assess reduction of amount of blood loss, need of transfusion products and outcome (length of stay, mortality) in patients with bleeding in comparison.

Detailed Description
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Von Willebrand Factor (vWF) is a key protein mediating platelet adhesion on the surface of damaged endothelia, initiating platelet-platelet aggregation and supporting platelet activation. It plays also an important role in protecting FVIII from early activation and clearance . The product's included coagulation factor VIII acts in in the activated form like the regular factor VIIIa. It takes part in the coagulation amplification by activating factor X to Xa together with factor IVa. Activation of factor X results in generating thrombin out of prothrombin. Wilate® is approved in Switzerland for prophylaxis and treatment of bleeding in patients suffering from von Willebrand disease and Haemophilia A. VWF is produced by the endothelial cells as a heterogeneous mixture of low and high molecular weight units. VWF is a ligand for receptors on the platelet surface and endothelial cells (GP1b-V-IX, αIIbβ3, αvβ3) mediating adhesion of platelets to each other or to the endothelium. Initial platelet adhesion is a crucial step in haemostatic functioning. Loss of platelets, vWF or blocking of these integrins due to the wide use of platelet aggregation inhibitors can cause bleeding. In case of severe blood loss, these conditions often result in mass transfusion. There is suggestive evidence from an in-vitro flow chamber model and from treatment of patients with severe vWF deficiency that increasing the concentration of vWF onto normal or high normal levels can enhance platelet adhesion independent from platelet count. This might translate into a better haemostatic effect of administered platelet concentrates in the bleeding patient and less need for transfusion of blood products (platelet concentrates), especially in clinical conditions with a high probability of low platelet count and low vWF activities (e.g., heart surgery with extracorporeal circulation, ECMO). To the best of our knowledge, no trial exists that investigated the effect of platelet transfusion in combination with the administration of balanced vWF in severe blood loss. The investigators hypothesize that simultaneous transfusion of platelets and balanced (1:1 vWF and FVIII) vWF compared to placebo reduces the overall need of transfusion of blood products.

Official Title
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Enhancement of the Haemostatic Effect of Platelets in the Presence of High Normal Concentrations of Von Willebrand Factor

Conditions
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Bleeding

Intervention / Treatment
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* Drug: Wilate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Admission to intensive care unit Patients needing platelet transfusion during or after surgery with or without prior treatment with single or dual antiplatelet agents (ASS, Prasugrel, Clopidogrel, Ticagrelor) Consent by the patient or a family member in addition to the consent of an independent ICU physician Exclusion Criteria: Patients receiving Factor VIII concentrate before inclusion of the study (Haemate ®) Women who are pregnant or breastfeeding Participation in another study with an investigational drug within the 30 days preceding and during the present study Overt Disseminated Intravascular Coagulation (DIC) Heparin-induced Thrombocytopenia (HIT) Thrombotic Thrombocytopenic Purpura (TTP) or Haemolytic uremic Syndrome (HUS) Idiopathic thrombocytopenic purpura (ITP) Sepsis Patients with known inherited thrombocytopathies Patients with known von Willebrand disease or Haemophilia A Patients with known hemato-oncological diseases Previous enrolment into the current study Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Platelet transfusion with Wilate ®<br> | Drug: Wilate<br>* Wilate ® will be given with platelets in cases of severe bleeding. Wilate ® is a 1:1 balanced mixture of von Willebrand Factor (2'000 IU) and Coagulation factor VIII (2'000 IU) and as such has anti-haemorrhagic potential. It is extracted from plasma, freeze-dried and virus-inactivated.<br>|
| Placebo Comparator: Platelet transfusion with Placebo<br> | Other: Placebo<br>* Empty placebo will be given with platelets in cases of severe bleeding.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of blood products | Number of blood products (fresh frozen plasma (FFP), red blood cells (RBC)) according to groups. | 48 hours |