COVID-19 Drugs: Ivermectin Reduces Mortality Rates In Hospitalized COVID-19 Patients In A Cohort Clinical Study Conducted In South Florida
: Medical Researchers from Broward Health Medical Center-South Florida, Drexel University College of Medicine and Florida International University have demonstrated that Ivermectin
reduces mortality rates in hospitalized COVID-19 patients according to a cohort clinical study conducted. https://www.medrxiv.org/content/10.1101/2020.06.06.20124461v1.full.pdf+html
The study findings were published in a preprint server and is currently being peer-reviewed.
The clinical study involved 280 patients hospitalized at four Broward Health hospitals in South Florida with confirmed SARS-CoV-2.
Patients mean age was 59.6 years (standard deviation 17.9), 45.4% female, of whom 173 were treated with ivermectin and 107 were given usual care. 27 identified patients were not reviewed due to multiple admissions, lack of confirmed COVID results during hospitalization, age less than 18, pregnancy, or incarceration.
Patients were categorized into two treatment groups based on whether they received at least one dose of ivermectin at any time during the hospitalization. Treatment decisions were at the discretion of the treating physicians. Severe pulmonary involvement at study entry was characterized as need for either FiO2 ≥50%, or noninvasive or invasive mechanical ventilation.
Patients in the Ivermectin group received at least one oral dose of ivermectin at 200 micrograms/kilogram in addition to usual clinical care. The decision to prescribe ivermectin, hydroxychloroquine, azithromycin or other medications was at the discretion of the treating physicians, however hospital guidelines were established for the use of these agents as well as for cardiac and QT monitoring for patients receiving hydroxychloroquine. Oxygen and ventilatory support were applied per the customary care.
In total, 307 patients were admitted for COVID-19 during the time period studied. 4 patients were not reviewed due to multiple admissions, 11 had no confirmed COVID testing at the time of the study, and 12 were excluded due to age younger than 18 years old, pregnancy, or incarceration. The remaining cohort of 280 patients was comprised of 173 treated with ivermectin and 107 in the usual care group. Follow up data for all outcomes were available through May 19th, 2020. No patients were lost to follow-up for the primary outcome. At the time of analysis, all patients in the cohort had met the endpoint of death, discharge alive, or awaiting transfer to a skilled facility.
Characteristics were similar between groups, however hypertension was more prevalent in the Ivermectin group, whereas the use of hydroxychloroquine and hydroxychloroquine plus azithromycin were higher in the usual care group. No other significant between-group differences were found among baseline characteristics or comorbidities, including age, race, cardiac comorbidities, or smoking status.
Overall mortality was significantly lower in the ivermectin group than in the usual care group (15.0% vs 25.2%, for ivermectin and usual care respectively, p=.03). Mortality was also lower for ivermectin treated patients in the subgroup of patients with severe disease (38.8% vs. 80.7%, p=.001).
Differences in extubation rates between groups were not significant and there was also no difference in length of hospital stay. Univariate analysis found that patients dying with COVID-19 infection were older, had higher white blood cell counts and lower absolute lymphocyte counts than survivors. Patients who died were also more likely to have been current or former smokers and have comorbid cardiac conditions, and were more likely to have severe pulmonary involvement and hypotension at study entry. In comparison to Caucasians, Blacks and Hispanics had lower odds of mortality in this cohort. In the multivariate analysis, adjusting for demographic factors, between-group differences in mortality risks, and concomitant use of hydroxychloroquine (with or without azithromycin), independent predictors of in-hospital mortality included treatment group, age, severe pulmonary disease category, and reduced lymphocyte count. Similarly, the Cox regression showed ivermectin was associated with a significantly lower hazard ratio for mortality of 0.37 (CI 0.19 - 0.70, p=.003). Complete case analysis on the entire cohort without missing data was similar (HR 0.40, 0.22- 0.74) p=.003).
In this multihospital retrospective cohort study, the researchers observed a significant association with ivermectin on survival for patients admitted with Covid-19. This association was also seen in the subset of patients with severe pulmonary disease. Similar to other studies, we noted that older age, cardiac disease, current or former smoking, more severe pulmonary involvement at presentation, higher white blood cell counts, and lower lymphocyte counts emerged as risk markers for in-hospital mortality. The overall mortality, and mortality in intubated patients, in the usual care group was similar to what was reported in previous studies.
In the Ivermectin group, thirteen patients received a second dose of Ivermectin (200 mcg/kg) on day 7, since they were still hospitalized. Due to the low numbers, the researchers did not perform any further analysis of the redosing.
They also did not observe any significant side-effect from Ivermectin use. They did not observe a significant difference in hospital length of stay between the groups (median 7 days for both groups). Possible explanation could include delay in discharging patients to other facilities (skilled nursing facilities, inpatient rehabs, etc) due to lag in obtaining required repeat COVID testing results. Need for mechanical ventilation was not adopted as outcome of interest, as national guidelines and practice patterns for intubation criteria changed throughout the length of the study.
The researchers did not find a lower mortality in the non-severe patients treated with ivermectin; however, the study was not powered to assess these differences as the overall mortality in non-severe patients was low. Similarly, the study was not powered to determine whether extubation rates were higher in the Ivermectin group.
These should be investigated further with a larger randomized controlled trial. The study has several limitations. Due to the retrospective observational nature of the study, despite adjustment for known cofounders, the researchers cannot exclude the possibility of unmeasured confounding factors. Although more of the control group was enrolled earlier in the study, suggesting the possibility of timing bias, this may be offset by preferential treatment of more severe patients with ivermectin early in the study due to low initial availability.
The researchers also did not find consistently better mortality outcomes with time over the short duration of this study. Most of the patients studied received hydroxychloroquine with or without azithromycin and the researchers are unable to determine whether these medications had an added benefit, or whether mortality would have been better in both groups without these agents.
However it was shown that ivermectin administration was significantly associated with lower mortality among patients with COVID-19, particularly in patients with more severe disease. Interpretations of these findings are tempered by the limitations of the retrospective design and the possibility of confounding. Appropriate dosing for this indication is not known; nor are the effects of ivermectin on viral load, or in patients with milder disease. Further studies in appropriately designed randomized trials are recommended before any conclusions can be made.
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