ITACTIC: Viscoelastic Assay-Guided Resuscitation in Major Trauma (2021)

“Among patients with trauma and major bleeding, transfusion guided by viscoelastic hemostatic assays, compared with transfusion guided by conventional coagulation tests, did not result in a statistically significant improvement in the primary outcome of survival free of massive transfusion at 24 hours.”

  • The ITACTIC Investigators

1. Publication Details

  • Trial Title: Viscoelastic Haemostatic Assay Augmented Centralised Bleeding Management in Major Trauma: A Multicentre, Randomised, Controlled Trial
  • Citation: Baksaas-Aasen K, Gall L, Stensballe J, et al. Viscoelastic haemostatic assay augmented centralised bleeding management in major trauma: a multicentre, randomised, controlled trial. Intensive Care Med. 2021;47(1):49-62. DOI: 10.1007/s00134-020-06282-y
  • Published: January 2021, in Intensive Care Medicine
  • Author: K. Baksaas-Aasen, on behalf of the ITACTIC collaborators
  • Funding: European Union Seventh Framework Programme; and others.

2. Keywords

  • Trauma, Hemorrhage, Coagulopathy, Viscoelastic Hemostatic Assays (VHA), Thromboelastography (TEG), Rotational Thromboelastometry (ROTEM), Massive Transfusion, Randomized Controlled Trial

3. The Clinical Question

  • In adult trauma patients with major bleeding (Population), does a transfusion strategy guided by viscoelastic hemostatic assays (VHA) (Intervention) compared to a strategy guided by conventional coagulation tests (CCT) (Comparison) improve the proportion of patients who are alive and free of massive transfusion at 24 hours (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Trauma-induced coagulopathy is a major driver of mortality in bleeding patients. Standard resuscitation protocols often involve fixed ratios of blood products. Viscoelastic hemostatic assays (VHA), such as TEG and ROTEM, are point-of-care tests that provide a rapid, comprehensive assessment of the entire clotting process.
  • Knowledge Gap: It was hypothesized that using VHA to guide a more personalized, goal-directed transfusion strategy could lead to faster correction of coagulopathy, reduced blood product use, and improved survival compared to relying on slower, conventional lab tests (CCTs) like PT/INR and platelet counts. However, this had not been proven in a large, multicenter randomized trial.
  • Proposed Hypothesis: The authors hypothesized that a VHA-guided transfusion strategy would be superior to a CCT-guided strategy in increasing the proportion of patients alive and free of massive transfusion at 24 hours.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, controlled trial (used to test the effectiveness of interventions).
  • Setting: 12 level 1 trauma centers in Europe and the United States.
  • Trial Period: Enrollment ran from April 2017 to December 2019.
  • Population:
    • Inclusion Criteria: Adult trauma patients (≥16 years) who had received at least one unit of red blood cells and were predicted to require a massive transfusion.
    • Exclusion Criteria: Included patients with non-survivable injuries or those who had received a massive transfusion before randomization.
  • Intervention: A VHA-guided transfusion strategy. Clinicians used results from either TEG or ROTEM, according to a specific algorithm, to guide the administration of blood products (FFP, cryoprecipitate, platelets).
  • Control: A CCT-guided transfusion strategy. Clinicians used results from conventional coagulation tests (PT/INR, fibrinogen, platelet count) to guide transfusions, following European guidelines.
  • Management Common to Both Groups: All patients received standard trauma care, including damage control surgery and the use of tranexamic acid.
  • Power and Sample Size: The authors calculated that a sample size of 392 patients would provide 80% power to detect a 15% absolute difference in the primary outcome. (Power is a study’s ability to find a real difference between treatments if one truly exists; 80% is the standard accepted level for clinical trials).
  • Outcomes:
    • Primary Outcome: A composite of the proportion of patients who were alive and free of massive transfusion (defined as <10 units of RBCs) at 24 hours after randomization.
    • Secondary Outcomes: Included 28-day mortality, the amount of blood products transfused, and the incidence of thromboembolic events.

6. Key Results

  • Enrollment and Baseline: 396 patients were randomized (198 to the VHA group and 198 to the CCT group). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: There was no significant difference in the primary composite outcome. 128 of 198 patients (65%) in the VHA group were alive and free of massive transfusion at 24 hours, compared with 120 of 198 patients (61%) in the CCT group (p=0.45).
  • Secondary Outcomes: There were no significant differences between the groups in 28-day mortality or in the total amount of blood products transfused.
  • Adverse Events: The incidence of serious adverse events, including thromboembolism, was similar in both groups.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a chi-square test.
  • Primary Outcome Analysis: The primary outcome was a comparison of the proportions of patients who met the composite endpoint between the two groups.
  • Key Statistic(s) Reported: The key statistics were the absolute rates of the primary outcome and the associated P-value.
  • Interpretation of Key Statistic(s):
    • P-value: The p-value of 0.45 for the primary outcome is much higher than the 0.05 threshold, indicating that the result was not statistically significant and very likely due to chance (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures: As the trial was neutral, ARR and NNT are not applicable.
  • Subgroup Analyses: No significant differences were found in any of the pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The multicenter, randomized, controlled design provided high-quality evidence on an important clinical question.
  • Generalizability: The inclusion of 12 major trauma centers in Europe and the US increases the applicability of the findings to similar high-resource settings.
  • Statistical Power: The study was adequately powered for its primary outcome.
  • Patient-Centered Outcomes: The primary outcome was a composite of survival and a major resource utilization endpoint (massive transfusion).

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was unblinded, which introduces a risk of performance bias.
  • External Validity (Generalizability): The study was conducted in high-performing trauma centers where the control group (CCT) received very rapid and aggressive resuscitation, which may have made it difficult for the VHA strategy to show a superior benefit.
  • Other: The primary outcome was a composite endpoint driven largely by the massive transfusion component, not mortality.

10. Conclusion of the Authors

  • The authors concluded that among patients with major trauma and bleeding, a transfusion strategy guided by viscoelastic hemostatic assays did not result in a significant improvement in the proportion of patients who were alive and free of massive transfusion at 24 hours, as compared with a strategy guided by conventional coagulation tests.

11. To Summarize

  • Impact on Current Practice: This was an important “negative” trial that challenged the growing assumption that VHA-guided resuscitation was superior to a modern, aggressive CCT-guided approach.
  • Specific Recommendations:
    • Patient Selection: For adult trauma patients with major hemorrhage.
    • Actionable Intervention: The results suggest that either a VHA-guided or a CCT-guided transfusion strategy is an acceptable approach, with no evidence of superiority for the more technologically advanced VHA strategy.
  • What This Trial Does NOT Mean: This trial does NOT mean that viscoelastic testing is not a useful tool. It only suggests that in a high-performing trauma system, a VHA-based algorithm was not superior to an aggressive CCT-based algorithm.
  • Implementation Caveats: The key to successful trauma resuscitation appears to be the presence of a clear, aggressive, and rapidly executed transfusion protocol, regardless of whether it is guided by VHA or CCT.

12. Context and Related Studies

  • Building on Previous Evidence: The ITACTIC trial (2021) was designed to provide a definitive answer to a question that had been explored in many smaller, often conflicting, studies.
  • Influence on Subsequent Research: The definitive neutral finding of this trial has been highly influential in shaping trauma resuscitation guidelines, which now generally support the use of either VHA or CCT to guide transfusion, depending on local resources and expertise.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The key unresolved question is whether VHA might still be superior in settings with slower turnaround times for conventional lab tests, or in specific patient subgroups.
  • Future Directions: Future research is focused on further refining goal-directed resuscitation protocols and on exploring the role of other hemostatic adjuncts in trauma.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, comparing a promising new technology against the established standard of care for a time-critical condition.
  • Methods: The multicenter RCT design was appropriate and robust. The main methodological weakness is the open-label design. A key strength is that the control arm represented a very high standard of modern care, making the comparison a fair test.
  • Results: The study reported a clear neutral finding for its primary outcome and all major secondary outcomes.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The high external validity of this pragmatic trial means its findings are broadly applicable to most modern, high-volume trauma centers. This is a classic example of a high-quality “negative” trial that was practice-changing by providing strong evidence that a more technologically advanced and expensive intervention is not necessarily superior to a well-executed standard approach.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
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