et al., J. Investig. Med., doi:10.1136/jim-2020-001747 (Peer Reviewed)
Small RCT with 100 patients, 48 with bromhexine added to SOC, showing slower viral- conversion but lower mortality and greater clinical improvement with bromhexine (not statistically significant with few deaths and very high recovery). The very large difference between unadjusted and adjusted results is due to much higher risk for patients with renal disease and the much higher prevalence of renal disease in the bromhexine group.
The study also shows 90% of patients in the control group had BMI>=30 compared to 0% in the treatment group, suggesting a possible problem with randomization. Due to the imbalance between groups, results were adjusted for BMI>30, smoking, and renal disease.
11 patients were lost to followup in the treatment group compared to zero in the control group, perhaps in part due to faster recovery in the treatment group. 9 patients were excluded from the treatment group because they did not want to take bromhexine after discharge. Therefore up to 29% of treatment patients may have been excluded because they recovered quickly.
Tolouian et al., 3/15/2021, Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 7 authors.
risk of death, 76.0% lower, RR 0.24, p = 0.43, treatment 48, control 52, Table 3, adjusted.
risk of no improvement, 75.9% lower, RR 0.24, p = 0.43, treatment 48, control 52, Table 2, adjusted.
risk of COVID-19 case, 74.5% higher, RR 1.75, p = 0.02, treatment 29 of 48 (60.4%), control 18 of 52 (34.6%), mid-recovery day 7.
Effect extraction follows pre-specified rules
prioritizing more serious outcomes. For an individual study the most serious
outcome may have a smaller number of events and lower statistical signficance,
however this provides the strongest evidence for the most serious outcomes
when combining the results of many trials.