Grouped countries into three different categories:
Include ivermectin in prophylaxis
Do not include ivermectin in prophylaxis
Do not do prophylaxis
Compared COVID-19 incidence between these three groups:
The fact that prophylaxis without ivermectin also showed a strong and statistically significant association with COVID-19 incidence suggests that other drugs could include additional candidates for the treatment and/or prevention of COVID-19
Conclusion: There seems to be an association rather than a causation of ivermectin use reducing COVID-19 incidence. However, we don’t know the rates of COVID-19 in these countries, crowding, testing availability, etc. There’s simply too much unknown information to make anything of this paper other than a hypothesis to study.
Evidence from Iraq [5]
Randomized controlled trial of 140 patients:
70 COVID-19 patients (48 mild-moderate, 11 severe, and 11 critical patients) treated with 200ug/kg PO of ivermectin qD for 2 to 3 days + 100mg PO doxycycline BID for 5 to 10 days + standard of care
70 COVID-19 patients (48 mild-moderate and 22 severe and zero critical patients) treated with standard of care alone
Mild to moderate disease = outpatients
Severe/Critical disease = inpatients
Results:
Ivermectin-Doxycycline reduced mean time to recovery from 17.9 to 10.61d in all recruited patients
In mild to moderate patients this reduction was from 13.66d to 6.34d
In severe patients this reduction was from 24d to 20d
This can have a tremendous effect on lowering the burden of disease and quickly freeing up hospital beds to other patients
Limitations:
Convenience sample: We have no idea how many patients total could have gotten treatment
Unclear what earlier means as there were no critical patients in the SOC arm
Non-blinded: Everyone knew what they were taking
Randomization method is flawed
Small study
No clear definition of recovery making this a subjective outcome that can bias the study
No idea if it’s the ivermectin or the doxycycline making the difference if you believe the difference
No information on patients to see if groups were balanced (i.e. demographics, underlying disease, etc.)
Conclusion: On the surface it seems Ivermectin with doxycycline reduced the time to recovery, percentage of patients who progress to more advanced stages of disease and reduced mortality. However, there were so many methodological issues I would not put any weight in these conclusions.
The ICON Study [7]
Retrospective observational cohort trial of consecutive patients hospitalized with COVID-19 from 4 hospitals in Florida
Reviewed charts of patients with COVID-19 treated with and without Ivermectin
This is the study that got everyone’s attention on Ivermectin as it was published in CHEST
Primary: All-cause in-hospital mortality
Results:
280 patients (173 treated with Ivermectin and 107 without)
Patients received at least one dose of Ivermectin 200mcg/kg + standard care vs standard care alone
A second dose of 200mcg/kg of Ivermectin could be given on day 7 at the discretion of the treating clinician
Univariate analysis showed lower mortality in ivermectin group (15.0%vs 25.2%; OR 0.52; 95% CI 0.29 to 0.96; p = 0.03)
Mortality also lower in patients with severe pulmonary involvement (need for FiO2 ≥50%, NIV, or IMV)
8% vs 80.7%; OR 0.15; 95% CI 0.05 to 0.47; p = 0.001
No difference in extubation rates or length of state
After multivariate adjustment for confounders, mortality difference remained significant (OR 0.27; 95% CI 0.09 to 0.80; p = 0.03)
Propensity matching was also used and found mortality to be significantly lower in ivermectin group (13.3% vs 24.5%; OR 0.47; 95% CI 0.22 to 0.99; p < 0.05) an 11.2% absolute risk reduction with a NNT of 8.9
Limitations:
Biggest limitation of this study is that patients in the Ivermectin group got steroids far more commonly than those who didn’t:
Unmatched Cohort: 39.8% vs 19.6%
Matched Cohort: 25.5% vs 21.4%
More of the control group was enrolled in the 1st weeks of the study suggesting a timing bias. We get better at caring for a new disease as time goes on
Conclusion: According to the authors, Ivermectin treatment was associated with lower mortality during treatment of COVID-19, especially in patients with severe pulmonary involvement. However more patients in the Ivermectin arm received corticosteroids than those who didn’t and the benefits seen in this trial may simply be due to this fact.
credited to ebelem
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