Thrombosomes® in Acute Thoracic Aortic Dissections

Study Overview
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Brief Summary
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The hypothesis is that administration of Thrombosomes® (TBX®) as hemostatic support when terminating the cardiopulmonary bypass (CPB) in patients undergoing emergency surgery for acute thoracic aortic dissection (aTAD) is safe and least as effective when compared to standard Platelet Concentrates (stPC).

Detailed Description
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The study is designed as an exploratory phase 2a, single-center randomized, controlled pilot investigator-initiated trial of administration of Thrombosomes® (TBX®) versus standard platelet concentrates (stPC) in 20 aTAD patients per arm. The patients will be enrolled in the study over a period of 15 months. TBX® is a novel, human platelet (thrombocyte) derived lyophilized (freeze dried) hemostatic blood product for treatment of bleeding due to thrombocytopenia, dysfunctional platelet disorders or platelet consumption. The patients will be randomized to administration of either TBX®, or stPC, as part of the Massive Transfusion Protocol (MTP) at the time of termination of the cardiopulmonary bypass (CPB) in addition to standard goal-directed hemostatic optimization based on results from thrombelastography (TEG).

Official Title
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Feasibility and Safety of Thrombosomes® on Time to Hemostasis in Patients Undergoing Emergency Surgery for Thoracic Aortic Dissections - a Randomized, Controlled, Open-label Investigator-initiated Pilot Trial

Conditions
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Thoracic Aortic Dissection

Intervention / Treatment
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* Biological: Thrombosomes®
* Biological: Standard platelet concentrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient eligible for emergency surgery on cardiopulmonary bypass pump for acute thoracic aortic dissections Age ≥ 18 years Exclusion Criteria: Documented refusal of blood transfusion Aortic dissection due to trauma Withdrawal from active therapy Known hypersensitivity to TBX: the active substance, any of the excipients Pregnancy (non-pregnancy confirmed by patient being postmenopausal (women >55 years of age) or having a negative urine-hCG).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel groups, patients entering in either intervention arm or standard treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thrombosomes®<br>Thrombosomes® (TBX®) up to 3 doses | Biological: Thrombosomes®<br>* The intervention with TBX® is to be administered as an intravenous infusion as hemostatic blood product as part of the Massive Transfusion Protocol (MTP).<br>* Other names: Freeze-dried platelets;|
| Active Comparator: Standard platelet concentrate<br>Standard platelet concentrate up to 3 doses | Biological: Standard platelet concentrate<br>* The administration of standard platelets is administrated, as part of the Massive Transfusion Protocol (MTP).<br>* Other names: stPC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to hemostasis during surgery | Defined by initiation of chest closure (temporary or final closure), the placement of the first sternal wire or wound vac (ioban or film), from administration of full dose protamine. | During procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bleeding during surgery | Bleeding during surgery as measured by suction, cell salvage, chest tubes, mediastinal drains, extracorporeal circulation (ECC), and in the field of surgery | During procedure | 
| Bleeding in chest tubes and mediastinal drainages on arrival in the ICU | Volume of bleeding in chest tubes and mediastinal drains from end of surgery to arrival in the Intensive Care Unit (ICU) | Average 3 hours | 
| Bleeding in mL in chest tube and mediastinal drainage at 24 hour after arrival in the ICU | Volume of bleeding in chest tubes and mediastinal drainages from arrival in the ICU to 24 hours after ICU arrival, measured in mL | 24 hours | 
| Bleeding in mL/kg in chest tube and mediastinal drainage at 24 hour after arrival in the ICU | Volume of bleeding in chest tubes and mediastinal drainages from arrival in the ICU to 24 hours after ICU arrival, measured in mL/kg | 24 hours | 
| Total number of blood product use during surgery | Number of blood products (RBC, fresh-frozen plasma (FFP), standard platelets (PLT) concentrate and/or Thrombosomes®) throughout the operation and prior to arrival at the ICU | During procedure | 
| Total volume of blood product use during surgery | Volume of blood products (RBC, fresh-frozen plasma (FFP), standard platelets (PLT) concentrate and/or Thrombosomes®) throughout the operation and prior to arrival at the ICU | During procedure | 
| Total number of blood product use during the first 24 hours in the ICU | Numbers of blood products (RBC, FFP, standard PLT) during the first 24 hours in the ICU | 24 hours | 
| Total units of blood product use during the first 24 hours in the ICU | Units of blood products (RBC, FFP, standard PLT) during the first 24 hours in the ICU | 24 hours | 
| Number of patients needing re-do surgery due to hemorrhage | Number of patients with need for re-do surgery due to hemorrhage in the first 24 hours postoperatively | 24 hours | 
| Sequential Organ Failure Assessment (SOFA) score during stay in ICU within 12 days | Sequential Organ Failure Assessment (SOFA) score during stay in ICU within 12 days, or until discharge from ICU, whichever comes first. Scale from 0 to 20 with 20 signifying severe organ failure | 12 days | 
| Hemostatic product use during surgery | Use of hemostatic products (fibrinogen concentrate, cryoprecipitate, recombinant factor VIIa) during surgery | During procedure | 
| Vasopressor free days within 30 days | Numbers of vasopressor free days in the ICU within 30 days | 30 days | 
| Ventilator free days | Numbers of ventilator free days in the ICU within 30 days | 30 days | 
| Renal replacement free days | Numbers of renal replacement free days in the ICU within 30 days | 30 days | 
| Length of stay in ICU | Numbers of days in the ICU | 30 days | 
| Length of stay in hospital | Numbers of days in the hospital | 30 days | 
| Mortality | 30-day mortality after intervention | 30 days | 
| Symptomatic thrombo-embolic events | Numbers of symptomatic thrombo-embolic events within 30 days after intervention | 30 days | 
| Serious adverse reactions/events | Number of serious adverse reactions/events within the first 12 days after intervention | 12 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surgery, Bleeding