Clinical trial NCT03613584: Von Willebrand Factor Concentrate During ECMO Support
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acquired Von Willebrand Disease
Lead sponsor: Tirol Kiniken GmbH
Sponsor class: OTHER
Collaborators: name: LFB BIOMEDICAMENTS
First posted: 2018-08-03
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Transfusion requirement of PRBC
timeFrame: Between start of IMP (Visit 2) until 24 hours after IMP-start (Visit 3)
Secondary outcomes:
measure: Transfusion requirements of other allogenic blood products
timeFrame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7)
measure: Requirements of coagulation factor concentrates
timeFrame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7)
measure: Number of vWF-HMW multimer bands
timeFrame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7)
measure: Assessment of thromboelastometry
timeFrame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7)
measure: Changes in thrombocytes
timeFrame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7)
measure: Renal function
timeFrame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7)
measure: Number of participants with bleeding events
timeFrame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7)
measure: Assessment vWF-HMW function
timeFrame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7)
measure: Assessment of activated partial thromboplastin time (aPTT) assay
timeFrame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7)
measure: Changes in red blood cell number
timeFrame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7)
measure: Number of participants with thromboembolic events
timeFrame: 36 hours after IMP-Stop
measure: Assessment of Prothrombin time (PT) assay
timeFrame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7)
measure: Assessment of activated clotting time (ACT)
timeFrame: Between start of ECMO (Visit 1) and 36 hours after ECMO Stop (Visit 7)
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medical University Innsbruck / Department for Anesthesia and Intensive Care Medicine
city: Innsbruck
country: Austria
facility: Medical University Innsbruck / Department for General and Surgical Critical Care Medicine
Study officials:
References:
citation: Tauber H, Streif W, Fritz J, Ott H, Weigel G, Loacker L, Heinz A, Velik-Salchner C. Predicting Transfusion Requirements During Extracorporeal Membrane Oxygenation. J Cardiothorac Vasc Anesth. 2016 Jun;30(3):692-701. doi: 10.1053/j.jvca.2016.01.009. Epub 2016 Jan 11.
citation: Tauber H, Ott H, Streif W, Weigel G, Loacker L, Fritz J, Heinz A, Velik-Salchner C. Extracorporeal membrane oxygenation induces short-term loss of high-molecular-weight von Willebrand factor multimers. Anesth Analg. 2015 Apr;120(4):730-6. doi: 10.1213/ANE.0000000000000554.
citation: Velik-Salchner C, Eschertzhuber S, Streif W, Hangler H, Budde U, Fries D. Acquired von Willebrand syndrome in cardiac patients. J Cardiothorac Vasc Anesth. 2008 Oct;22(5):719-24. doi: 10.1053/j.jvca.2007.05.013. Epub 2007 Aug 3. No abstract available.