Evidence from Countries Using Prophylactic Ivermectin vs Those not Using Prophylactic Ivermectin

  • 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:


Evidence from Countries Using Prophylactic Ivermectin vs Those not Using Prophylactic Ivermectin
  • 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:


Evidence from Countries Using Prophylactic Ivermectin vs Those not Using Prophylactic Ivermectin
  • 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


 


3 views0 comments