Trial reportTrials2020
Accuracy of time to treatment estimates in the CRASH-3 clinical trial: impact on the trial results.
Trial report in Trials, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01402882 (Tranexamic Acid for the Treatment of Significant Traumatic Brain Injury), which is not on this map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Tranexamic Acid for the Treatment of Significant Traumatic Brain Injury: an International Randomised, Double Blind Placebo Controlled Trial
Who cites it
0 citing papers in PubMed, 6 citations in OpenAlex.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEarly treatment with tranexamic acid may reduce deaths after traumatic brain injury (TBI). In mild and moderate TBI, there is a time to treatment interaction, with early treatment being most beneficial. Time to treatment was recorded by clinicians and is subject to error. Using monitoring data from the CRASH-3 trial, we examine the impact of errors in time to treatment on estimated treatment effects.
methodsThe CRASH-3 trial was a randomised trial of the effect of tranexamic acid on death and vascular occlusive events in 12,737 TBI patients. This analysis includes the 8107 patients with a Glasgow coma scale score of 9 to 15 since previous analyses showed that these patients benefit most from early treatment. Clinician-recorded time to treatment was checked against ambulance and hospital records for 1368/12,737 (11%) patients. Patients who died were preferentially selected for monitoring and we monitored 36% of head injury deaths. We describe measurement errors using Bland-Altman graphs. We model the effect of tranexamic acid on head injury death using logistic regression with a time-treatment interaction term. We use regression calibration, multiple imputation and Bayesian analysis to estimate the impact of time to treatment errors.
resultsClinicians rounded times to the nearest half or full hour in 66% of cases. Monitored times were also rounded and were identical to clinician times in 63% of patients. Times were underestimated by an average of 9 min (95% CI - 85, 66). There was more variability between clinician-recorded and monitored times in low- and middle-income countries than in high-income countries. The treatment effect estimate at 1 h was greater for monitored times OR = 0.61 (95% CI 0.47, 0.81) than for clinician-recorded times OR = 0.63 (95% CI 0.48, 0.83). All three adjustment methods gave similar time to treatment interactions. For Bayesian methods, the treatment effect at 1 h was OR = 0.58 (95% CI 0.43, 0.78). Using monitored times increased the time-treatment interaction term from 1.15 (95% CI 1.03, 1.27) to 1.16 (95% CI 1.05, 1.28).
conclusionsAccurate estimation of time from injury to treatment is challenging, particularly in low resource settings. Adjustment for known errors in time to treatment had minimal impact on the trial results.
trial registrationClinicalTrials.gov NCT01402882 . Registered on 25 July 2011.
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