Recombinant vWF Concentrate and ECMO

Bleeding Disorder Clinical Trial

Official title: Safety and Tolerability of Recombinant Von Willebrand Factor Concentrate in Adult ECMO Patients With Major Bleeding: A Phase I Study

Status Not yet recruiting

Clinical Trial Summary

Adult patients on extracoporeal membrane oxygenation (ECMO) frequently experience bleeding, which is in part caused by acquired von Willebrand syndrome (vWS). Prior in vitro studies have shown that the addition of recombinant von Willebrand Factor (vWF) to ECMO patient blood samples, normalizes platelet adhesion and thrombus formation. This study is a phase I study, where adult ECMO patients with refractory bleeding will be treated with recombinant vWF a single time. The primary objectives are to evaluate the safety, tolerability, and pharmacokinetics of recombinant vWF in adult ECMO patients.

Clinical Trial Description

Coagulopathic bleeding is a common complication during ECMO. Multiple studies suggest that major bleeding occurs in 30-70% of adult ECMO patients, with higher bleeding rates in post-cardiotomy shock and veno-arterial (VA) ECMO patients. The pathophysiology of ECMO-induced coagulopathy is complex with multiple factors contributing, including loss of large VWF multimers, thrombocytopenia, increased tissue factor pathway inhibitor levels, and platelet surface glycoprotein (GP)1ba shedding. Adult ECMO patients almost universally develop acquired von Willebrand syndrome due to loss of large VWF multimers. In a study by Kalbhenn et al., acquired von Willebrand syndrome occurred within the first 6 hours of ECMO initiation in all patients (N=59) and returned to normal within 24 hours of ECMO decannulation. The loss of large VWF multimers that occurs in ECMO patients leads to poor platelet adhesion at an injury site and excess bleeding, which in some cases can become life-threatening. In a prior observational study, the investigators found that when adult ECMO patients with acquired von Willebrand syndrome were treated with plasma-derived vWF concentrate, it increased plasma ristocetin cofactor activity (RCo), increased the RCo-VWF antigen ratio, and improved clinical hemostasis. This preliminary data suggests that use of VWF may help to reduce bleeding in ECMO patients and is safe. Recombinant VWF has superior ultra-large multimer content, and thus it may be even better suited to treat acquired von Willebrand syndrome, which is represented by severe loss of large vWF multimers, similar to Type 2a von Willebrand disease. Further, recombinant VWF has a longer plasma half-life than plasma-derived VWF and may be safer because it contains no Factor VIII. Factor VIII activity is often supranormal during ECMO and overaccumulation of Factor VIII can increase thrombotic risk, particularly when there is blood stasis. In two prior in vitro studies, the investigators found that when recombinant VWF was added to ECMO patient blood samples, primary hemostasis/platelet adhesion returned towards normal. In a study that compared the addition of recombinant VWF to plasma-derived VWF, the investigators found that recombinant VWF improved primary hemostasis more, while having minimal impact on thrombin generation. These data suggest that recombinant VWF may be more effective in restoring primary hemostasis, and also may have a superior safety profile. The current study will investigate the safety and tolerability of recombinant VWF in adult ECMO patients with major bleeding. ;

Related Conditions & MeSH terms

• Bleeding Disorder
• Blood Coagulation Disorders
• Hemorrhage
• Hemostatic Disorders

• NCT number: NCT06118372
• Study type: Interventional
• Source: University of Virginia
• Contact: Michael Mazzeffi, MD
• Phone: 434-924-9520
• Email: syy4wa@uvahealth.org
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: January 1, 2024
• Completion date: December 31, 2026