Thrombosomes® in Acute Thoracic Aortic Dissections (TTAD)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Thoracic Aortic Dissection
• Intervention / Treatment: Biological: Thrombosomes®; Biological: Standard platelet concentrate

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jakob Stensballe, MD, PhD; Phone Number: +4535458587; Email: Jakob.stensballe@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Rigshospitalet, Copenhagen University Hospital
    • Contact: Jakob Stensballe, MD, PhD; Phone Number: +45 3545 8587; Email: jakob.stensballe@regionh.dk
    • Principal Investigator: Annette Ulrich, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jakob Stensballe, MD, PhD
• Collaborators: Cellphire Therapeutics, Inc.
• Investigators: Principal Investigator: Annette Ulrich, MD, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2023
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: February 15, 2023
• First Submitted That Met QC Criteria: March 15, 2023
• First Posted (Actual): March 16, 2023

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Surgery; Bleeding
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aneurysm; Aneurysm, Dissecting
• Other Study ID Numbers: H-22061913

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes