Bleeding DisorderPhase 1NCT06118372
Recombinant vWF Concentrate and ECMO
A Phase 1 study testing Recombinant von Willebrand Factor in people with Bleeding Disorder, run by University of Virginia at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bleeding Disorder
- What is being tested?
- Recombinant von Willebrand Factor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Oct 2024to 28 Feb 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (18 years or greater)
- On extracorporeal membrane oxygenation
- Major bleeding defined by CTCAE class 3 or greater
- Off systemic anticoagulation for at least 4 hours
Who cannot join
- Platelet count less than 40 x 109/L
- International normalized ratio> 2.0
- Fibrinogen less than 150 mg/dL
- Current participation in another clinical trial (interventional)
- Heparin induced thrombocytopenia (active)
- Acute liver failure, as indicated by bilirubin >20 mg/dL or new onset hepatic encephalopathy
Show all 13Show fewer
- Patient or legally authorized representative unable to give informed consent
- Allergy to recombinant von Willebrand Factor or any component of the product based on prior exposure
- Of childbearing age and positive pregnancy test during the same hospital admission, a pregnancy test will be mandatory for all women of child-bearing age
- Known congenital or acquired thrombophilia
- History of deep venous thrombosis, pulmonary embolism, circuit thrombosis, disseminated intravascular coagulation (DIC), ischemic stroke, ST elevation myocardial infarction (STEMI), or arterial thrombosis in the last 3 months.
- History of hypersensitivity to vWF concentrate
- Known history of vWF antibodies
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UVA Hospital
Charlottesville, Virginia, 22903
Michael Mazzeffi, MD, 434-924-9520, syy4wa@uvahealth.org
Keita Ikeda, PhD, 434-924-2283, KI2D@uvahealth.org
About this study
Official title: Safety and Tolerability of Recombinant Von Willebrand Factor Concentrate in Adult ECMO Patients With Major Bleeding: A Phase I Study
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.
Read the detailed 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.
- Conditions
- Bleeding Disorder
- Being tested
- Recombinant von Willebrand Factor
- Medical subject headings
- Hemostatic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant von Willebrand FactorDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment with recombinant vWF | Experimental | 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. Receives: Drug: Recombinant von Willebrand Factor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days after treatment
Area under the plasma concentration curve from zero to infinity (h × U/dL)
Pharmacokinetic parameter
Measured: 96 hours after treatment
Plasma half-life (hours)
Pharmacokinetic parameter
Measured: 96 hours after treatment
Mean residence time (hours)
Pharmacokinetic parameter
Measured: 96 hours after treatment
Clearance (mL/kg per hour)
Pharmacokinetic parameter
Measured: 96 hours after treatment
Volume at a steady state (dL/kg)
Pharmacokinetic parameter
Measured: 96 hours after treatment
Maximum concentration (U/dL)
Pharmacokinetic parameter
Measured: 96 hours after treatment
Time to maximum concentration (hours)
Pharmacokinetic parameter
Measured: 96 hours after treatment
Incremental recovery ([U/dL]/[U VWF: RCo/kg] for VWF)
Pharmacokinetic parameter
Measured: 96 hours after treatment
Secondary outcomes (2)
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.
Measured: 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.
Measured: 24 hours after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2023
- Study start3 Oct 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Bleeding DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label non-randomized phase I trial.
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Mazzeffi, MD, University of Virginia
- Investigators
- Michael Mazzeffi, MD, Principal investigator, UVA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06118372
- Sponsor's protocol ID
- HSR230248
- Status last verified
- Feb 2026
- First submitted
- 21 Sep 2023
- Last updated
- 5 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mazzeffi M, Bathula A, Tabatabai A, Menaker J, Kaczorowski D, Madathil R, Galvagno S, Pasrija C, Rector R, Tanaka K, Herr D. Von Willebrand Factor Concentrate Administration for Acquired Von Willebrand Syndrome- Related Bleeding During Adult Extracorporeal Membrane Oxygenation. J Cardiothorac Vasc Anesth. 2021 Mar;35(3):882-887. doi: 10.1053/j.jvca.2020.06.083. Epub 2020 Jul 3.
PubMed 32758410Mazzeffi M, Hasan S, Abuelkasem E, Meyer M, Deatrick K, Taylor B, Kon Z, Herr D, Tanaka K. Von Willebrand Factor-GP1balpha Interactions in Venoarterial Extracorporeal Membrane Oxygenation Patients. J Cardiothorac Vasc Anesth. 2019 Aug;33(8):2125-2132. doi: 10.1053/j.jvca.2018.11.031. Epub 2018 Nov 22.
PubMed 30595484Mazzeffi M, Henderson R, Krause E, Rabin J, Madathil R, Chow J, Grazioli A, Meyer M, Wu Z, Tanaka K. In Vitro Comparison of Recombinant and Plasma-Derived von Willebrand Factor Concentrate for Treatment of Acquired von Willebrand Syndrome in Adult Extracorporeal Membrane Oxygenation Patients. Anesth Analg. 2022 Feb 1;134(2):312-321. doi: 10.1213/ANE.0000000000005831.
PubMed 34903705Mazzeffi M, Gonzalez-Almada A, Wargowsky R, Ting L, Moskowitz K, Hockstein M, Davison D, Levy JH, Tanaka KA. In Vitro Treatment of Extracorporeal Membrane Oxygenation Coagulopathy with Recombinant von Willebrand Factor or Lyophilized Platelets. J Cardiothorac Vasc Anesth. 2023 Apr;37(4):522-527. doi: 10.1053/j.jvca.2022.12.028. Epub 2022 Dec 30.
PubMed 36690556
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Tolerability of Recombinant Von Willebrand Factor Concentrate in Adult ECMO Patients With Major Bleeding: A Phase I Study
- ClinicalTrials.gov ID
- NCT06118372
- Acronym / sponsor ID
- HSR230248
- Conditions
- Bleeding Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 3 Oct 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 7 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label non-randomized phase I trial.
| Arm | Type | Receives |
|---|---|---|
| Treatment with recombinant vWF | Experimental | Drug: Recombinant von Willebrand FactorECMO 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult patients (18 years or greater)
- On extracorporeal membrane oxygenation
- Major bleeding defined by CTCAE class 3 or greater
- Off systemic anticoagulation for at least 4 hours
Key exclusion criteria (13 listed)
- Platelet count less than 40 x 109/L
- International normalized ratio> 2.0
- Fibrinogen less than 150 mg/dL
- Current participation in another clinical trial (interventional)
- Heparin induced thrombocytopenia (active)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant von Willebrand FactorRecombinant 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. | Drug | Treatment with recombinant vWF |
Primary outcome
Serious Adverse Events
Time frame: 30 days after treatment
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.
Area under the plasma concentration curve from zero to infinity (h × U/dL)
Time frame: 96 hours after treatment
Pharmacokinetic parameter
Plasma half-life (hours)
Time frame: 96 hours after treatment
Pharmacokinetic parameter
Mean residence time (hours)
Time frame: 96 hours after treatment
Pharmacokinetic parameter
Clearance (mL/kg per hour)
Time frame: 96 hours after treatment
Pharmacokinetic parameter
Volume at a steady state (dL/kg)
Time frame: 96 hours after treatment
Pharmacokinetic parameter
Maximum concentration (U/dL)
Time frame: 96 hours after treatment
Pharmacokinetic parameter
Time to maximum concentration (hours)
Time frame: 96 hours after treatment
Pharmacokinetic parameter
Incremental recovery ([U/dL]/[U VWF: RCo/kg] for VWF)
Time frame: 96 hours after treatment
Pharmacokinetic parameter
2 secondary outcomes
Change in bleeding severity class
Time frame: 24 hours after treatment
Change in bleeding/drain output volume from existing surgical drains
Time frame: 24 hours after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2026.
- Results publication: PubMed 32758410Mazzeffi M, Bathula A, Tabatabai A, Menaker J, Kaczorowski D, Madathil R, Galvagno S, Pasrija C, Rector R, Tanaka K, Herr D. Von Willebrand Factor Concentrate Administration for Acquired Von Willebrand Syndrome- Related Bleeding During Adult Extracorporeal Membrane Oxygenation. J Cardiothorac Vasc Anesth. 2021 Mar;35(3):882-887. doi: 10.1053/j.jvca.2020.06.083. Epub 2020 Jul 3.
- Results publication: PubMed 30595484Mazzeffi M, Hasan S, Abuelkasem E, Meyer M, Deatrick K, Taylor B, Kon Z, Herr D, Tanaka K. Von Willebrand Factor-GP1balpha Interactions in Venoarterial Extracorporeal Membrane Oxygenation Patients. J Cardiothorac Vasc Anesth. 2019 Aug;33(8):2125-2132. doi: 10.1053/j.jvca.2018.11.031. Epub 2018 Nov 22.
- Results publication: PubMed 34903705Mazzeffi M, Henderson R, Krause E, Rabin J, Madathil R, Chow J, Grazioli A, Meyer M, Wu Z, Tanaka K. In Vitro Comparison of Recombinant and Plasma-Derived von Willebrand Factor Concentrate for Treatment of Acquired von Willebrand Syndrome in Adult Extracorporeal Membrane Oxygenation Patients. Anesth Analg. 2022 Feb 1;134(2):312-321. doi: 10.1213/ANE.0000000000005831.
- Results publication: PubMed 36690556Mazzeffi M, Gonzalez-Almada A, Wargowsky R, Ting L, Moskowitz K, Hockstein M, Davison D, Levy JH, Tanaka KA. In Vitro Treatment of Extracorporeal Membrane Oxygenation Coagulopathy with Recombinant von Willebrand Factor or Lyophilized Platelets. J Cardiothorac Vasc Anesth. 2023 Apr;37(4):522-527. doi: 10.1053/j.jvca.2022.12.028. Epub 2022 Dec 30.
- Individual participant dataSharing planned: No
Related trials for Bleeding Disorder
RecruitingObservational study
Prevalence and Associated Factors of High BMI and Periodontitis in Thai Adults Aged Under 60 Years
Diabete Mellitus, Dyslipidaemia
RecruitingObservational study
Bleeding Disorder of Unknown Cause in the Netherlands
Hemorrhagic Disorders, Bleeding Disorder of Unknown Cause
RecruitingObservational study
Impact of IV Iron on Bleeding Symptoms in Iron Deficient Patients With Inherited Bleeding Disorders
Bleeding Disorders, Iron
Not yet recruiting
Effectiveness of Interactive Techniques on Oral Hygiene Skills in a Group of Autistic Egyptian Children
Autism Disorder, Autism Spectrum Disorder (ASD
RecruitingObservational study
Observational Study of Platelet Dysfunction Assessed by Thromboelastography in Cardiovascular Surgery (DISPLATEG)
Blood Platelet Disorders, Cardiac Surgery
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael Mazzeffi, MD principal investigator
UVA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Recombinant von Willebrand Factor in people with Bleeding Disorder, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michael Mazzeffi, MD (434-924-9520, syy4wa@uvahealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serious Adverse Events (time frame: 30 days after treatment). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06118372, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2026; AzTrials last refreshed its copy on 29 Oct 2026.