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

• ClinicalTrials.gov Identifier: NCT02593877
• Recruitment Status: Completed
• First Posted: November 1, 2015
• Last Update Posted: August 29, 2018
• Sponsor: Queen Mary University of London
• Collaborators: Oslo University Hospital; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Klinikum der Universität Köln; Rigshospitalet, Denmark; Oxford University Hospitals NHS Trust; Barts & The London NHS Trust; European Commission
• Information provided by (Responsible Party): Queen Mary University of London

Tracking Information

• First Submitted Date: October 15, 2015
• First Posted Date: November 1, 2015
• Last Update Posted Date: August 29, 2018
• Actual Study Start Date: June 1, 2016
• Actual Primary Completion Date: July 3, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 30, 2015)

Proportion of subjects alive and free of massive transfusion [ Time Frame: 24 hours ]

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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 18, 2017)

• 6hr Mortality [ Time Frame: 6 hours ]
  All-cause mortality at 6-hours post admission
• 24hr Mortality [ Time Frame: 24 hours ]
  All-cause mortality at 24-hours post admission
• 28d Mortality [ Time Frame: 28-days ]
  All-cause mortality at 28-days post admission
• 90d Mortality [ Time Frame: 90-days ]
  All-cause mortality at 90-days post admission
• Duration of coagulopathy [ Time Frame: 28-days post admission ]
  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).
• Severity of coagulopathy [ Time Frame: 28-days post admission ]
  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).
• Proportion of patients with corrected coagulopathy after first 8U RBC [ Time Frame: 28-days post admission ]
  Proportion of patients with corrected coagulopathy after first 8U RBC
• Time to hemostasis [ Time Frame: 28-days post admission ]
  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).
• Time spent in coagulopathic condition until haemostasis [ Time Frame: 28-days post admission ]
  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.
• 6hr Blood products transfused [ Time Frame: 6 hours ]
  Total blood products (RBC, plasma, platelets alone and in total) transfused in first 6hours after admission
• 24hr Blood products transfused [ Time Frame: 24 hours ]
  Total blood products (RBC, plasma, platelets alone and in total) transfused in first 24hours after admission
• 28d Ventilator-free days [ Time Frame: 28 days ]
  Calculated by the subtracting the number of days spent on mechanical ventilation from 28.
• 28d ICU-free days [ Time Frame: 28 days ]
  Calculated by the subtracting the number of days spent on intensive care unit from 28.
• Length of stay [ Time Frame: 28 days ]
  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.
• Symptomatic thromboembolic events [ Time Frame: 28 days ]
  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).
• Transfusion-related complications [ Time Frame: 28-days ]
  Incidence, category and severity of acute transfusion reactions will be defined according to UK SHOT (United Kingdom Serious Hazards of Transfusion)
• Organ dysfunction [ Time Frame: 28-days ]
  Organ dysfunction shall be measured as Sequential Organ Failure Assessment (SOFA) score from admission to day 28 or discharge
• 28d/discharge QoL [ Time Frame: 28 days ]
  Health-Related Quality of Life (HRQoL) will be measured at 28 day post admission or upon discharge if sooner
• 90d QoL [ Time Frame: 90 days ]
  Health-Related Quality of Life (HRQoL) will be measured at 90 day post admission

Original Secondary Outcome Measures (submitted: October 30, 2015)

• 6hr Mortality [ Time Frame: 6 hours ]
  All-cause mortality at 6-hours post admission
• 24hr Mortality [ Time Frame: 24 hours ]
  All-cause mortality at 24-hours post admission
• 28d Mortality [ Time Frame: 28-days ]
  All-cause mortality at 28-days post admission
• 90d Mortality [ Time Frame: 90-days ]
  All-cause mortality at 90-days post admission
• Duration of coagulopathy [ Time Frame: 28-days post admission ]
  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).
• Severity of coagulopathy [ Time Frame: 28-days post admission ]
  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).
• Proportion of patients with corrected coagulopathy after first 8U RBC [ Time Frame: 28-days post admission ]
• Time to hemostasis [ Time Frame: 28-days post admission ]
  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).
• Time spent in coagulopathic condition until haemostasis [ Time Frame: 28-days post admission ]
  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.
• 6hr Blood products transfused [ Time Frame: 6 hours ]
  Total blood products (RBC, plasma, platelets alone and in total) transfused in first 6hours after admission
• 24hr Blood products transfused [ Time Frame: 24 hours ]
  Total blood products (RBC, plasma, platelets alone and in total) transfused in first 24hours after admission
• 28d Ventilator-free days [ Time Frame: 28 days ]
  Calculated by the subtracting the number of days spent on mechanical ventilation from 28.
• 28d ICU-free days [ Time Frame: 28 days ]
  Calculated by the subtracting the number of days spent on intensive care unit from 28.
• Length of stay [ Time Frame: 28 days ]
  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.
• Symptomatic thromboembolic events [ Time Frame: 28 days ]
  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).
• Transfusion-related complications [ Time Frame: 28-days ]
  Incidence, category and severity of acute transfusion reactions will be defined according to UK SHOT (United Kingdom Serious Hazards of Transfusion)
• Organ dysfunction [ Time Frame: 28-days ]
  Organ dysfunction shall be measured as SOFA score from admission to day 28 or discharge
• 28d/discharge QoL [ Time Frame: 28 days ]
  Health-Related Quality of Life (HRQoL) will be measured at 28 day post admission or upon discharge if sooner
• 90d QoL [ Time Frame: 90 days ]
  Health-Related Quality of Life (HRQoL) will be measured at 90 day post admission

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy
• Official Title: 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
• Brief Summary: 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.

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment

Condition

• Hemorrhage
• Coagulopathy
• Trauma

Intervention

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)

Study Arms

• 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
  Intervention: Device: VHA algorithm
• 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

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 28, 2018): 412
• Original Estimated Enrollment (submitted: October 30, 2015): 392
• Actual Study Completion Date: July 30, 2018
• Actual Primary Completion Date: July 3, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, Germany, Netherlands, Norway, United Kingdom

Administrative Information

• NCT Number: NCT02593877
• Other Study ID Numbers: 010770
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Queen Mary University of London
• Study Sponsor: Queen Mary University of London

Collaborators

• Oslo University Hospital
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Klinikum der Universität Köln
• Rigshospitalet, Denmark
• Oxford University Hospitals NHS Trust
• Barts & The London NHS Trust
• European Commission

Investigators

• Study Director: Karim Brohi, FCRS FRCA; Queen Mary University of London, Barts Health NHS Trust
• Principal Investigator: Christine Gaarder, MD; Oslo University Hospital

• PRS Account: Queen Mary University of London
• Verification Date: August 2018