Viscoelastic Tests (VET) Versus Conventional Coagulation Tests (CCT) for Management of Trauma-Induced Coagulopathy

Official title

Viscoelastic Tests (VET) Versus Conventional Coagulation Tests (CCT) for Management of Trauma-Induced Coagulopathy: Opened, Randomized, Two-Parallel, Controlled Trial.VISCOTAC

Overview

Traumatic coagulopathy is a complex, multifactorial event that occurs in 20-30% of patients on admission. It increases mortality, and its treatment is one of the main priorities in the early management of severely injured patients. Diagnosis of coagulopathy has traditionally been based on conventional coagulation tests (CCTs), which provide an assessment of patients' coagulation in over 60 minutes. Over the past fifteen years, viscoelastic tests (VETs) have been proposed, providing a more rapid result (≤ 10 min) and can guide the administration of labile blood products (LBP). Various studies, mainly retrospective, have shown that the use of VETs is associated with a significant reduction in the use of LBP and the incidence of massive transfusions (MT). For example, it has been showed that the use of VETs was accompanied by a reduction in the administration of LBP and more particularly of RBC (Red blood cell concentrate) (4.8 units vs. 1.9 units). The investigators obtained the same result on a larger number of patients, with a further reduction in the administration of other LBP and in the incidence of MT (33% vs. 8%, p\<0.01). However, the main limitation of these 2 studies is that the results may not have been due solely to the use of ROTEM, but rather to a care package combining the use of ROTEM with the administration of tranexamic acid and the implementation of Damage Control Surgery techniques. To avoid this methodological criticism, we recently compared 2 contemporary French cohorts (2012-2019), in which patients had similar management of traumatic injuries, with the exception of the type of coagulation tests: CCT vs. VET. The use of VET s was associated with an increase in the number of patients alive at 24h without MT (76% vs. 55%, p\<0.001), but also with a sharp reduction in the administration of all LBPs. This composite criterion associating the occurrence of a MT with survival at 24 hours after hospital admission was the primary endpoint of the randomized iTACTIC study. iTACTICS was published in 2021, and aimed to compare in severely injured patients 2 strategies for the diagnosis and treatment of coagulopathies, based on CCT in one arm and VET in the other. In this work, the use of VET was not associated with an improvement in the proportion of patients alive at 24 hours without MT (64% vs. 67%, OR 1.15, CI95%: 0.8-1.7), nor with any of the other criteria studied. The main limitation of this study is that less than a third of the patients included had a coagulopathy on admission. The probability of receiving LBP was therefore low. In the subgroup of the most severe patients, an improvement in the primary endpoint was observed for patients randomized to the VET group. The small sample size and subgroup analysis, however, limited the significance of this result. All these elements suggest that it is necessary : * to use a composite endpoint rather than a single endpoint (mortality) for the evaluation of VET-based strategies, combining early mortality with the occurrence of a transfusion event. * conduct a randomized trial comparing the use of VETs with that of CCTs in trauma patients with a high probability of coagulopathy on admission to hospital.

Interventions

• Device Viscoelastic Tests (ROTEM)
  Viscoelastic Tests (2-6 tests for the study over the first 24 hours)

Primary outcome measures

• The survival without massive transfusion 24 hours after admission in the VET arm as compared to the CCT arm. [Time frame: 24hours after admission]

Secondary outcome measures (11)

• Number and proportion of patient receiving labile blood products, at 4, 6 and 24 hours after hospital admission. [Time frame: 4, 6 and 24 hours after hospital admission]
• Number and proportion of patients receiving fibrinogen concentrates as well as the quantity administered (in grams), at 6 and 24 hours after hospital admission [Time frame: 6 and 24 hours after hospital admission]
• Number and proportion of patients who received massive transfusion, time critical transfusion and Rescue therapy [Time frame: 24 hours]
• Number of RBCs received from admission to ICU discharge (or at 28 days maximum after randomization (Day 28)). [Time frame: At discharge or at 28 days maximum after randomization (Day 28))]
• Number and proportion of patients with a "Sepsis-related Organ Failure Assessment" (SOFA) score > 5, after randomization, at H24, Day 2, Day 3, Day 4. [Time frame: 4 days]
• Ventilator-free days, vasopressor days, renal replacement therapy days [Time frame: 28 days]
• Total volume (mL) of fluids received at 24-hours including blood products and fluid resuscitation (crystalloids and colloids). [Time frame: H24]
• Number and proportion of patients who died at H6, H24 and Day 28 [Time frame: 28 days]
• Length of stay in the intensive care unit up to Day 28. [Time frame: 28 days]
• Timing and the number of hemorrhage control procedures (surgery, interventional radiology) in the first 6-hours following admission. [Time frame: 6 hours]
• Number and proportion of patients with grade 3 and 4 adverse events related to the management strategy between randomization and Day 28 [Time frame: 28 days]

Eligibility criteria

Inclusion criteria

• Age 18 years or older
• Blunt or penetrating injury
• Less than 3 hours after a trauma AND less than 1 hour after trauma room admission
• One of the following criteria:

• Severe trauma in shock (shock index > 0.9 or SBP < 90 mmHg) or with anemia (hemoglobin < 11 g.dL-1) and at least 1 of the following criteria:

• Positive extended-FAST (Focused Assessment with Sonography for Trauma, ultrasound) finding liquid
• Severe bone injury :

• Fracture of at least two long bones
• Amputation above the knee or elbow
• Open fracture of the pelvis and/or mechanically unstable pelvis
• Severe trauma with a high probability of having a TIC (PTratio > 1.20) according to the TIC score (score value ≥ 6 - cf. appendix 2)
• Emergency procedure with secondary informed consent signed by the patient

Exclusion criteria

• Known pregnancy at admission
• Transfer from another hospital
• Cardiac arrest before randomization
• Patient with devastating injuries expected to die within the first hour post-admission
• Massive head injury with GCS 3 and bilateral mydriasis
• Pre-hospital transfusion of RBCs unit or coagulation factors concentrates
• No tranexamic acid before hospital admission
• Patient with uncontrolled major bleeding on arrival with direct admission to the operating room for rescue surgery
• Conventional or viscoelastic assay before inclusion/randomization
• Hypothermia < 33°C
• Known use of oral anticoagulants (VKA or DOACs)
• Known congenital hemostasis abnormality
• Predictable transfer to another hospital <12 hours after admission
• Patients protected by articles L1121-6 and L1121-7 of the Public Health Code, adults subject to legal protection measures
• Patient not affiliated to a social security scheme
• Patient included in other interventional study on coagulopathy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

France · 7 centers

• Service d'Anesthésie - Réanimation, CHU Angers — Angers
• Service d'Anesthésie - Réanimation, Groupe Hospitalier Pellegrin CHU de Bordeaux — Bordeaux
• Service de Réanimation - CH Annecy Genevois — Epagny METZ Tessy
• Service d'Anesthésie - Réanimation, Hôpital Michallon- CHU Grenoble — La Tronche
• Service d'Anesthésie - Réanimation, HCL Edouard Herriot — Lyon
• Service d'Anesthésie-Réanimation, HCL Lyon Sud — Pierre-Benité
• Service d'Anesthésie - Réanimation, HIA St Anne Toulon — Toulon

Identifiers

NCT: NCT06820879 · 69HCL22_0937

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗