Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy (iTACTIC)

A Multi-centre, Prospective, Randomized Controlled Study to Compare Outcomes of Viscoelastic Haemostatic Assay (VHA)-Guided Resuscitation Versus Conventional Resuscitation Support in Haemorrhaging Trauma Patients

This trial compares the haemostatic effect of viscoelastic haemostatic assay (VHA)-guided transfusion strategy versus non-VHA guided transfusion strategy in haemorrhaging trauma patients. Half of the randomised patients will receive VHA-led management of bleeding, whilst the other half will receive massive transfusion protocol resuscitation using conventional coagulation tests.

Study Overview

• Status: Completed
• Conditions: Hemorrhage; Trauma; Coagulopathy
• Intervention / Treatment: Device: VHA algorithm

Detailed Description

Trauma is the most frequent cause of death in persons aged under 40, with half of these deaths resulting from uncontrolled bleeding. 1 in 4 of all severely injured and shocked patients develop a clotting abnormality termed Trauma Induced Coagulopathy (TIC) within minutes of injury, which causes blood to continue being lost from the body faster than it can be stemmed. Many more injured patients will go on to develop different types of coagulopathy at different times during the course of their treatment, either as a result of their body's ongoing response to trauma or as a consequence of their clinical care. Ultimately coagulopathic patients have increased blood transfusion requirements and suffer more adverse outcomes (e.g. multi organ failure).

Current management of coagulopathic, haemorrhaging trauma patients comprises the unguided transfusion of large volumes of red blood cells and clotting product supplements. Without rapidly available and validated diagnostics, products are delivered empirically to patients blind to the type and severity of TIC they may have or indeed even if they do not have TIC. This study will compare outcomes of viscoelastic haemostatic assay (VHA)-guided resuscitation versus conventional management of critically bleeding trauma patients. The hypothesis is that goal-directed haemostatic resuscitation of coagulopathic bleeding trauma patients will yield improved outcomes and reduced blood product demand, compared to empiric massive transfusion therapy.

• Study Type: Interventional
• Enrollment (Actual): 412
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Copenhagen University Hospital
• Germany
  • Cologne, Germany
    • Kliniken der Stadt Koln gGmbH
• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Centre
• Norway
  • Oslo, Norway
    • Oslo University Hospital
• United Kingdom
  • Nottingham, United Kingdom
    • Queens Medical Centre
  • Oxford, United Kingdom
    • John Radcliffe Hospital
  • Greater London
    • London, Greater London, United Kingdom, E1 1BB
      • The Royal London Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Adult trauma patients (according to local definitions) will be enrolled if they:

• Present with hemorrhagic shock at any time from the time of injury until admission to the emergency department (where shock is defined by HR>100 b/min and/or systolic BP<90 mmHg) AND activate the local massive transfusion protocol
• Randomized within 3 hours of injury and 1 hour of admission to the emergency department
• Agreement is provided on behalf of incapacitated patients by Personal Consultee or Nominated Consultee (e.g.trauma team leader)

Exclusion Criteria:

• Any inclusion criteria are not met

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: VHA algorithm; Massive transfusion protocol resuscitation aiming at ratio 1:1:1 of blood components (RBC 1: plasma 1: platelets 1) and VHA-guiding further resuscitation with blood products and procoagulant factors	Device: VHA algorithm; Analysis of more than 2,200 trauma subjects has enabled the definition of clinically-relevant VHA thresholds (i.e. ROTEM® and TEG® parameters) and patterns by which it is possible to rapidly identify coagulopathic patients and anticipate the need for massive transfusion. These threshold parameters have been defined and applied to the generation of an evidence-based targeted treatment algorithm (i.e. the Intervention)
NO_INTERVENTION: Control; Massive transfusion protocol resuscitation aiming at ratio 1:1:1 of blood components (RBC 1: plasma 1: platelets 1) and conventional coagulation tests guiding further resuscitation with blood products and procoagulant factors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects alive and free of massive transfusion	Proportion of subjects at 24 hours post-admission who are alive and free of massive transfusion (i.e. received 10 or more units of red blood cells within 24 hours)	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6hr Mortality	All-cause mortality at 6-hours post admission	6 hours
24hr Mortality	All-cause mortality at 24-hours post admission	24 hours
28d Mortality	All-cause mortality at 28-days post admission	28-days
90d Mortality	All-cause mortality at 90-days post admission	90-days
Duration of coagulopathy	The time spent in coagulopathic state, as defined by Prothrombin Time / International Ratio (PTr) PTr >1.2) from Admission until the point of hemostasis (itself defined as having occurred at the end of the first hour free of red cell transfusions and the treating clinicians believe primary hemostasis has been achieved).	28-days post admission
Severity of coagulopathy	Defined by the area under the Prothrombin Time / International Ratio (PTr) curve from Admission to the point of haemostasis (where time of hemostasis is defined as having occurred at the end of the first hour free of red cell transfusions and the treating clinicians believe primary hemostasis has been achieved).	28-days post admission
Proportion of patients with corrected coagulopathy after first 8U RBC	Proportion of patients with corrected coagulopathy after first 8U RBC	28-days post admission
Time to hemostasis	Time from Admission to the point of hemostasis (where time of hemostasis is defined as having occurred at the end of the first hour free of red cell transfusions and the treating clinicians believe primary hemostasis has been achieved).	28-days post admission
Time spent in coagulopathic condition until haemostasis	Time of haemostasis is defined the period from Admission to the point as having occurred at the end of the first hour free of red cell transfusions and the treating clinicians believe primary hemostasis has been achieved. Coagulopathy defined as PTr >1.2.	28-days post admission
6hr Blood products transfused	Total blood products (RBC, plasma, platelets alone and in total) transfused in first 6hours after admission	6 hours
24hr Blood products transfused	Total blood products (RBC, plasma, platelets alone and in total) transfused in first 24hours after admission	24 hours
28d Ventilator-free days	Calculated by the subtracting the number of days spent on mechanical ventilation from 28.	28 days
28d ICU-free days	Calculated by the subtracting the number of days spent on intensive care unit from 28.	28 days
Length of stay	Length of stay will be recorded in days, for the total number spent in ICU and in Hospital. If the patient is in the hospital at any time point during a day, this day will be considered a hospital day.	28 days
Symptomatic thromboembolic events	Symptomatic venous thromboembolic events shall be recorded, as confirmed by radiology. Other thromboembolic events such as myocardial infarction and/or stroke shall be identified by standard clinical diagnostic investigation(s).	28 days
Transfusion-related complications	Incidence, category and severity of acute transfusion reactions will be defined according to UK SHOT (United Kingdom Serious Hazards of Transfusion)	28-days
Organ dysfunction	Organ dysfunction shall be measured as Sequential Organ Failure Assessment (SOFA) score from admission to day 28 or discharge	28-days
28d/discharge QoL	Health-Related Quality of Life (HRQoL) will be measured at 28 day post admission or upon discharge if sooner	28 days
90d QoL	Health-Related Quality of Life (HRQoL) will be measured at 90 day post admission	90 days

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Collaborators: Oslo University Hospital; Rigshospitalet, Denmark; Barts & The London NHS Trust; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); European Commission; Oxford University Hospitals NHS Trust; Klinikum der Universität Köln
• Investigators: Study Director: Karim Brohi, FCRS FRCA, Queen Mary University of London, Barts Health NHS Trust; Principal Investigator: Christine Gaarder, MD, Oslo University Hospital

Publications and helpful links

General Publications

• Baksaas-Aasen K, Gall L, Eaglestone S, Rourke C, Juffermans NP, Goslings JC, Naess PA, van Dieren S, Ostrowski SR, Stensballe J, Maegele M, Stanworth SJ, Gaarder C, Brohi K, Johansson PI. iTACTIC - implementing Treatment Algorithms for the Correction of Trauma-Induced Coagulopathy: study protocol for a multicentre, randomised controlled trial. Trials. 2017 Oct 18;18(1):486. doi: 10.1186/s13063-017-2224-9.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2016
• Primary Completion (ACTUAL): July 3, 2018
• Study Completion (ACTUAL): July 30, 2018

Study Registration Dates

• First Submitted: October 15, 2015
• First Submitted That Met QC Criteria: October 30, 2015
• First Posted (ESTIMATE): November 1, 2015

Study Record Updates

• Last Update Posted (ACTUAL): August 29, 2018
• Last Update Submitted That Met QC Criteria: August 28, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Hemostasis; Trauma; Transfusion; Resuscitation; Coagulopathy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Coagulation Disorders; Wounds and Injuries; Hemorrhage
• Other Study ID Numbers: 010770

Plan for Individual participant data (IPD)

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