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

NCT ID: NCT04555785

Last Updated: 2024-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-01

Study Completion Date

2028-11-30

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.

Conditions

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Bleeding

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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Platelet transfusion with Wilate ®

Group Type EXPERIMENTAL

Wilate

Intervention Type DRUG

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.

Platelet transfusion with Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Empty placebo will be given with platelets in cases of severe bleeding.

Interventions

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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.

Intervention Type DRUG

Placebo

Empty placebo will be given with platelets in cases of severe bleeding.

Intervention Type OTHER

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Basel, Switzerland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Martin Siegemund, Prof. Dr. MD

Role: STUDY_CHAIR

University Hospital, Basel, Switzerland

Locations

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University Hospital Basel

Basel, , Switzerland

Site Status RECRUITING

Countries

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Switzerland

Central Contacts

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Martin Siegemund, Prof. Dr. MD

Role: CONTACT

Phone: 0041613286414

Email: [email protected]

Andrea Blum, med. pract.

Role: CONTACT

Phone: 0041796903886

Email: [email protected]

Facility Contacts

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Martin Siegemund, MD

Role: primary

Alexa Hollinger, MD

Role: backup

References

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Ledergerber K, Hollinger A, Zimmermann S, Todorov A, Trutmann M, Gallachi L, Gschwandtner LA, Ryser LA, Gebhard CE, Bolliger D, Buser A, Tsakiris DA, Siegemund M. Impact of Additional Administration of von Willebrand Factor Concentrates to Thrombocyte Transfusion in Perioperative Bleeding in Cardiac Surgery. Transfus Med Hemother. 2023 Jul 11;51(1):22-31. doi: 10.1159/000530810. eCollection 2024 Feb.

Reference Type DERIVED
PMID: 38314243 (View on PubMed)

Herrmann G, Blum A, Bolliger D, Achermann R, Estermann A, Gebhard CE, Henn A, Huber J, Singh J, Todorov A, Zehnder T, Zellweger N, Buser A, Tsakiris DA, Hollinger A, Siegemund M. Enhancement of the haemostatic effect of platelets in the presence of high normal concentrations of von Willebrand factor for critically ill patients needing platelet transfusion-a protocol for the will-plate randomised controlled trial. Trials. 2023 Jan 20;24(1):47. doi: 10.1186/s13063-022-06876-8.

Reference Type DERIVED
PMID: 36670471 (View on PubMed)

Other Identifiers

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2020-02106

Identifier Type: -

Identifier Source: org_study_id