4.1 Limitations
respiratory failure, deaths
RESPIRATORY FAILURE
The ATTAC-19 trial is not without its limitations. It is important to mention the current trial did identify a decrease in respiratory failure and all-cause mortality for the Aggrenox group compared to SOC alone, despite these data not reaching statistical significance. For instance, Aggrenox resulted in nearly half the number of deaths compared to the control group (n = 4 vs 7). Unfortunately, one patient could not be contacted in the Aggrenox group despite repeated efforts. It is possible that with additional patients, this difference would become statistically significant. The sample size for the current study was acquired with the goal to detect a relative between-group difference of 20% reduction on the COVID-19 ordinal scale discussed above. Twenty percent reduction was chosen to determine the sample size as we included only hospitalized patients ranging from COVID-ordinal scale 4 to 7 and we considered that a 1-point change in patient’s COVID-ordinal scale would be a significant improvement in hospitalized patient’s clinical status, such as improving from invasive ventilation to non-invasive ventilation. Previous larger studies have varied in their methods to plan an appropriate sample size which could detect a meaningful intervention effect, and there has been a lack of standard methods across trials especially given the lack of historical data for COVID-19 treatments which could inform these analyses. Other trials also examining ordinal scale outcomes have include larger percent reductions between groups (eg, 40%) [The current study was an open-label, single site design and thus is inherently subject to ascertainment bias on the outcome of respiratory failure and also a possible selection bias. While we believe that it was clinically evident which patients indeed required high flow oxygen or some form of non-invasive/invasive ventilation therapy, and therefore did not likely interfere with our results, it is possible that our sample represented a different group of patients compared to that of the general population. Other studies have reported much higher mortality rates during similar study periods [