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Von Willebrand Factor Concentrate During ECMO Support

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ClinicalTrials.gov Identifier: NCT03613584
Recruitment Status : Recruiting
First Posted : August 3, 2018
Last Update Posted : August 3, 2018
Sponsor:
Collaborator:
LFB BIOMEDICAMENTS
Information provided by (Responsible Party):
Tirol Kiniken GmbH

Brief Summary:
During treatments with extracorporeal circuits such as extracorporeal membrane oxygenation (ECMO) degradation of high molecular weight (HMW) of von Willebrand factor (vWF) multimers occur leading to an acquired von Willebrand disease. This disease is associated with increased bleeding and requirement for the transfusion with allogenic blood products especially packed red blood cells (PRBCs). A continuous treatment with von Willebrand factor concentrate (vWFC) may restore the multimers and bleeding can be avoided. Therefore a randomized, double-blind, prospective, controlled, two-arm clinical trial was designed, comparing patients receiving vWFC versus placebo.

Condition or disease Intervention/treatment Phase
Acquired Von Willebrand Disease Drug: Von Willebrand Factor Drug: Saline Solution Phase 2

Detailed Description:

Increased shear stress during mechanical circulatory support (MCS) by extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VAD) can provoke premature degradation of high molecular weight (HMW) of von Willebrand factor (vWF) multimers. In patients with intractable cardiac and/or respiratory failure requiring emergency ECMO support, the investigators recently demonstrated an essential decrease in high molecular weight (HMW) vWF multimer bands 24 and 48 hours after initiation of ECMO compared to baseline. Blood loss and transfusion requirement during and shortly after ECMO support may be strengthened by loss of HMW vWF multimers.

Administration of vWF concentrates may support restoration of primary hemostasis in patients during ECMO support. Consequently the need for packed red blood cells (PRBCs) during ECMO support may be reduced thus positively influencing morbidity and mortality of ECMO patients. The investigators hypothesize, that treatment with vWF concentrate reduces the need for PRBCs during ECMO support. Therefore the primary aim of this clinical trial is to find out if the need of PRBCs differs in the group receiving a von Willebrand factor concentrate (vWFC), or the placebo group (saline).

This clinical trial is planned as a randomized, double-blind, prospective, controlled, two-arm, two-center study. Patients with intractable cardiac and/or respiratory failure requiring emergency ECMO support undergoing surgery (Department of Anaesthesiology and Intensive Care Medicine) or treated at the General and Surgical Intensive Care Unit (ACI), Traumatologic Intensive Care Unit (TICU), Cardiologic Intensive Care Unit (CCU) or the ICU of the Department of Visceral, Transplant and Thoracic Surgery at the Hospital Innsbruck (Tirol Kliniken GmbH), Austria will be enrolled in the study when meeting the inclusion- and exclusion criteria. If a patient meets the inclusion criteria and is recruited for the study, the patient will be randomized either to the group receiving vWFC or placebo S. Before the implementation of the ECMO the Baseline investigations need to be conducted. As soon as they are completed the ECMO cannula can be inserted.

The administration of the Investigational Medicinal Product (IMP) will be start within 24h after ECMO installation. Directly before IMP-start blood samples (Visit 2) will be drawn. After 24h (Visit 3), 60h (Visit 4) and on day 5 (Visit 5) of the start of the study medication visits will be conducted, whereas on day 5 (Visit 5) no special laboratory (measurement of HMW vWF) will be analyzed. If ECMO can be terminated, a visit (Visit 6) directly before the stop of the ECMO will be conducted. 36 h after the termination of the ECMO Visit 7 (termination) will be performed. If the ECMO is needed longer than 7 days, the administration of the IMP will be stopped on day 7 and a visit after 36 hours of IMP-stop will be done for safety reasons but without special laboratory. After 30 days an interview will be performed with the treating physician.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: The vWFC or placebo will be prepared by the local hospital pharmacy or independent nurses from another ward (on holidays and weekends). To keep the blinding for the treating physicians and the study team syringes and lines with light protection (orange color) will be used. So the color of the medication (colorless to slightly yellowish) cannot be distinguished.
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo-controlled Pilot Trial to Investigate the Administration of Von Willebrand Factor Concentrate (Willfact®, LFB France) in Adult Patients During Extracorporeal Membrane Oxygenation
Actual Study Start Date : April 16, 2018
Estimated Primary Completion Date : March 10, 2021
Estimated Study Completion Date : March 10, 2021


Arm Intervention/treatment
Active Comparator: Group W (von Willebrand factor concentrate)
The patient receives von Willebrand factor concentrate (vWFC) as a bolus of 25 IU/kg followed by a continuous infusion of 50 IU/kg/24h until the weaning from ECMO is completed or if ECMO is needed longer than 7 days, the administration of the Investigational Medicinal Product (IMP) will be stopped on the 7th day.
Drug: Von Willebrand Factor
Bolus and continuous infusion of the Investigational Medicinal Product (IMP) during extracorporeal membrane oxygenation (ECMO)

Placebo Comparator: Group S (standard therapy with saline solution)
The patient receives the standard therapy plus an additional volume of saline solution equivalent to the amount of von Willebrand factor concentrate (vWFC) the patient would receive in Group W to keep the blind. The volume is given according to the VWFC-solution (0.25 ml/kg BW) what would be resulting from the patient's weight followed by a continuous saline infusion (0.50 ml/kg BW) until the weaning from ECMO is completed or if ECMO is needed longer than 7 days, the Investigational Medicinal Product (IMP) administration is stopped on the 7th day.
Drug: Saline Solution
Bolus and continuous infusion of the Investigational Medicinal Product (IMP) during extracorporeal membrane oxygenation (ECMO)




Primary Outcome Measures :
  1. Transfusion requirement of PRBC [ Time Frame: Between start of IMP (Visit 2) until 24 hours after IMP-start (Visit 3) ]
    Difference in the number of red blood cells concentrates between the treatment arms per day


Secondary Outcome Measures :
  1. Transfusion requirements of other allogenic blood products [ Time Frame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7) ]
    Difference in the number of other high risk allogenic transfusion products (fresh frozen plasma and platelet concentrate) between the treatment arms per day

  2. Requirements of coagulation factor concentrates [ Time Frame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7) ]
    Amount of coagulation factor concentrates given during ECMO support between the treatment arms per day

  3. Number of vWF-HMW multimer bands [ Time Frame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7) ]
    Number of vWF multimer bands measured via SDS-agarose gel electrophoresis between the treatment arms

  4. Assessment of thromboelastometry [ Time Frame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7) ]
    Difference in thromboelastometry between the treatment arms

  5. Changes in thrombocytes [ Time Frame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7) ]
    Difference in platelet number

  6. Renal function [ Time Frame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7) ]
    Difference in the daily urine output

  7. Number of participants with bleeding events [ Time Frame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7) ]
    Number of patients with bleeding events assessed by a bleeding score based on Mazzeffi et al 2013

  8. Assessment vWF-HMW function [ Time Frame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7) ]
    vWF function (vWF:Ag, vWF:RCo, and F:VIII) via photooptical measurement between the treatment arms

  9. Assessment of activated partial thromboplastin time (aPTT) assay [ Time Frame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7) ]
    aPTT assay [seconds] between the treatment arms

  10. Changes in red blood cell number [ Time Frame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7) ]
    Differences in red blood cell number and hemoglobin between the treatment arms

  11. Number of participants with thromboembolic events [ Time Frame: 36 hours after IMP-Stop ]
    Number of participants with thromboembolic events as assessed via duplex ultrasonic investigation of the cervical vessels (Carotis und Vertebralis) and major leg veins

  12. Assessment of Prothrombin time (PT) assay [ Time Frame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7) ]
    PT assay [%] between the treatment arms

  13. Assessment of activated clotting time (ACT) [ Time Frame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7) ]
    ACT assay [seconds] between the treatment arms



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with the need of veno-arterial or veno-venous ECMO for a minimum of 48 hours
  • Age ≥ 18 years

Exclusion Criteria:

  • Patient with known thromboembolic event in the last 30 days
  • Inevitable lethal course
  • Severe Liver failure: Quick < 30 %
  • Pregnancy
  • Patient with known refusal of a participation in this clinical trial
  • Active participation in another clinical trial
  • Any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study or confound the ability to interpret data from the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03613584


Contacts
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Contact: Mirjam Bachler, PhD 0043512504 ext 80451 mirjam.bachler@tirol-kliniken.at

Locations
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Austria
Medical University Innsbruck / Department for Anesthesia and Intensive Care Medicine Recruiting
Innsbruck, Austria, 6020
Contact: Mirjam Bachler, PhD    0043512504 ext 80451    mirjam.bachler@tirol-kliniken.at   
Principal Investigator: Corinna Velik-Salchner, MD         
Medical University Innsbruck / Department for General and Surgical Critical Care Medicine Recruiting
Innsbruck, Austria, 6020
Contact: Mirjam Bachler, PhD    0043512504 ext 80451    mirjam.bachler@tirol-kliniken.at   
Principal Investigator: Dietmar Fries, MD         
Sponsors and Collaborators
Tirol Kiniken GmbH
LFB BIOMEDICAMENTS

Publications:
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Responsible Party: Tirol Kiniken GmbH
ClinicalTrials.gov Identifier: NCT03613584     History of Changes
Other Study ID Numbers: ECMO-vWFC
First Posted: August 3, 2018    Key Record Dates
Last Update Posted: August 3, 2018
Last Verified: July 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Von Willebrand Diseases
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Blood Platelet Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Pharmaceutical Solutions