The comments regarding our recent post about the limitations of the CRASH-2 trial focus on definitions of trial design and purpose, the relative importance of those limitations in reducing the potential value of the CRASH-2 trial and the utility of Thromboelastography to assist in determining the need for TXA in trauma resuscitation. In response to these recent posts regarding the CRASH-2 trial, we refer to the table which is the foundation of our referenced comments regarding the limitations of the CRASH-2 trial. This table is taken from the review article on TXA in trauma by Napolitano et al (1) (foot note #2 in our post) which can also be found on Scott Weingart’s EM CRIT podcast #67 update on TXA (2). Note the reference to the 100% follow up, absence of adverse events, concern about possible inadequate reporting and other limitations of this large study of 20,211 patients from predominantly low to moderate income countries.
On the #67 EM CRIT podcast, Dr. Weingart has also reproduced in verbatim fashion the indications for TXA in trauma from this same Napolitano et al review on TXA in trauma. He can be quoted:
“In adult trauma patients with severe hemorrhagic shock (SBP <= 75 mm Hg), with known predictors of fibrinolysis, or with known fibrinolysis by TEG (LY30 > 3%).” (2)
Note the reference to the TEG….
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With regards to the observed increased rate of DVT/PE in the TXA treated patients from the MATTERs trial (3) please refer to comments in our post taken from Gruen RJ, Jacobs IG and Reade MC, on behalf of the PATCH trial.(4) The table below from the MATTERs trial demonstrates the 12 and 9 times increased rate of DVT and PE in the TXA treated patients.(3) This is indicated by the blue arrow. The significance of this increased rate of thrombosis is a matter of hypothesis in the discussion where the authors of the MATTERs trial note that: “it is plausible that the higher rates of thrombotic events relate to the TXA.”
Regardless of the CRASH-2 type of trial, whether it is an effectiveness or efficacy trial for example, the value of the trial should be determined by how well the authors can respond to the many limitations that are posed by the table above from Napolitano et al. For example, is the 28 day 100% follow up of 20,211 patients in low to moderate income countries a concern?
I conclusion, I turn to the wise words of Dr. Martin Schreiber, Chief of Trauma, Critical Care and Acute Care Surgery at the Oregon Health & Science University. As a seasoned trauma surgeon with many years of both clinical and research experience, Dr. Schreiber was invited by the FDA and NIH in 2010 (soon after the release of the CRASH-2 trial results) to rendered his wise opinion about the use of hemostatic agents such as rFVIIa, Prothrombin Complex Concentrate and TXA to curtail bleeding in trauma:
“Interestingly, and I think we learn this very, very well from the Factor VII process, the use of these drugs may not be justified based on the data that we have. And I am truly hoping that we don’t go through the same process with prothrombin complex concentrate and tranexamic acid that we did with Factor VII and then we get good prospective randomized trials we find out that these drugs are not — really are not indicated. And I think the bottom line here is that that we really haven’t found a way to beat that qualified trauma surgeon with the $0.50 silk suture. There are no magic bullets when it comes to drugs for stopping bleeding.” (5)
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