Enhancement of the Haemostatic Effect of Platelets in the Presence of High Normal Concentrations of Von Willebrand Factor (Will-Plate)

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.

Study Overview

• Status: Recruiting
• Conditions: Bleeding
• Intervention / Treatment: Drug: Wilate; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Martin Siegemund, Prof. Dr. MD; Phone Number: 0041613286414; Email: martin.siegemund@usb.ch
• Study Contact Backup: Name: Andrea Blum, med. pract.; Phone Number: 0041796903886; Email: andrea.blum@hotmail.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
    • Contact: Martin Siegemund, MD; Phone Number: +41613286414; Email: martin.siegemund@usb.ch
    • Contact: Alexa Hollinger, MD; Phone Number: +41613286508; Email: alexa.hollinger@usb.ch
    • Sub-Investigator: Lukas Gantner, MD
    • Sub-Investigator: Katrin Ledergerber, MD candidate

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Platelet transfusion with Wilate ®	Drug: Wilate; 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.
Placebo Comparator: Platelet transfusion with Placebo	Other: Placebo; Empty placebo will be given with platelets in cases of severe bleeding.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Study Chair: Martin Siegemund, Prof. Dr. MD, University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: September 14, 2020
• First Posted (Actual): September 21, 2020

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2020-02106

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No