A Phase 1 interventional study of Recombinant von Willebrand Factor in Bleeding Disorder, sponsored by University of Virginia. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-05.
Sponsored by University of Virginia · Phase 1, Interventional, and Treatment
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.
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.
361 studies on the registry are indexed under Hemostatic Disorders; 65 are open to participants now.
This study's planned enrollment of 12 is below the median of 60 across 171 interventional studies indexed under Hemostatic Disorders.
Browse Hemostatic Disorders studies →University of Virginia is the lead sponsor of 675 studies on the registry; 138 are open to participants now.
Of its 61 completed or terminated interventional studies of FDA-regulated products, 42 (69%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECMO patients with major bleeding who are enrolled in the trial will receive treatment with recombinant von Willebrand Factor a single time. The dose will be 50 IU/kg and the drug will be given intravenously.
Drug: Recombinant von Willebrand Factor
Recombinant von Willebrand Factor is a drug that is currently FDA approved to treat patients with certain types of von Willebrand Disease. In the current trial it will be used to treat ECMO patients who have acquired von Willebrand syndrome.
Serious Adverse Events
Events that 1) cause death, 2) are life-threatening, 3) cause permanent damage, 4) required intervention to prevent harm, or 5) are otherwise serious and jeopardize the patient's safety.
Time frame: 30 days after treatment
Area under the plasma concentration curve from zero to infinity (h × U/dL)
Pharmacokinetic parameter
Time frame: 96 hours after treatment
Plasma half-life (hours)
Pharmacokinetic parameter
Time frame: 96 hours after treatment
Mean residence time (hours)
Pharmacokinetic parameter
Time frame: 96 hours after treatment
Clearance (mL/kg per hour)
Pharmacokinetic parameter
Time frame: 96 hours after treatment
Volume at a steady state (dL/kg)
Pharmacokinetic parameter
Time frame: 96 hours after treatment
Maximum concentration (U/dL)
Pharmacokinetic parameter
Time frame: 96 hours after treatment
Time to maximum concentration (hours)
Pharmacokinetic parameter
Time frame: 96 hours after treatment
Incremental recovery ([U/dL]/[U VWF: RCo/kg] for VWF)
Pharmacokinetic parameter
Time frame: 96 hours after treatment
Change in bleeding severity class
The study's secondary endpoint will be any change in consensus definitions in Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 bleeding class 24 hours after treatment with Vonvendi.
Time frame: 24 hours after treatment
Change in bleeding/drain output volume from existing surgical drains
Change in total amount of bleeding/output from existing surgical drains will be a secondary study outcome.
Time frame: 24 hours after treatment
Plan to share: No
Started Oct 2024 (actual). Primary completion is estimated for Dec 2026, 26 months after the start.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.