Characterization of adverse events in injured patients at risk of hemorrhagic shock: a secondary analysis of three harmonized prehospital randomized clinical trials
Year: 2024
Type: article
Abstract: Background The reporting of adverse events (AEs) is required and well defined in the execution of clinical trials, but is poorly characterized particularly in prehospital trials focusing on traumatic injury. In the setting of prehospital traumatic injury trials, no literature currently exists analyzing the clinical implications of AEs and their associations with mortality and morbidity. We sought to analyze AEs from three prehospital hemorrhagic shock trials and characterize their time course, incidence, severity, associated clinical outcomes, and relatedness. Methods We performed a secondary analysis of three prehospital randomized clinical trials. We analyzed AEs at both the patient level as well as the individual AE level. We categorized patients who had no AEs, a single documented AE and those with multiple events (>1 AE). We characterized AE timing, severity, relatedness and attributable mortality outcomes. Results We included 1490 patients from the three harmonized clinical trials, with 299 (20.1%) individual patients having at least a single AE documented with 529 AEs documented overall as a proportion of patients had multiple events. Over 44% of patients had a death-related misclassified AE. Patients with at least a single documented AE had a significantly higher 28-day mortality (log-rank χ2=81.27, p<0.001) compared with those without an AE documented. Patients with a single AE had a significant higher mortality than those with multiple AEs, potentially due to survival bias (log-rank χ2=11.80, p=0.006). When relatedness of each individual AE was characterized, over 97% of AEs were classified as ‘definitely not related’ or ‘probably not related’ to the intervention. Conclusions AEs in hemorrhagic shock trials are common, occur early and are associated with mortality and survival bias. The potential for inaccurate reporting exists, and education and training remain essential for appropriate treatment arm comparison. The current results have important relevance to injury-related clinical trials. Trial registration numbers NCT01818427 , NCT02086500 and NCT03477006 . Level of evidence II.
Source: Trauma Surgery & Acute Care Open
Authors: John M Lorence, Jack K Donohue, Nidhi Iyanna, Francis X Guyette, Elizabeth Gimbel, Joshua B Brown, Brian J Daley, Brian J Eastridge, Richard S Miller, Raminder Nirula, Brian G Harbrecht, Jeffrey A Claridge, Herb A Phelan, Gary Vercruysse, Terence O'Keeffe, Bellal Joseph, Matthew D Neal, Jason L Sperry
Institutions: University of Pittsburgh, University of Tennessee Health Science Center, The University of Texas at San Antonio Health Science Center, JPS Health Network, University of Utah, University of Louisville, MetroHealth Medical Center, Case Western Reserve University, The University of Texas Southwestern Medical Center, University of Michigan, Augusta University, University of Arizona
Language: English
Subfield: Emergency Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,100
OpenAlex ID: W4400054984