https://www.aafp.org/journals/afp/explore/covid-19-daily-briefs.html
Coronavirus (COVID-19) Daily Research Briefs
July 29, 2020, Research Update
United States/Canadian RCT of Hydroxychloroquine for Patients with Early, Nonsevere COVID-19 Finds No Benefit. It has been hypothesized that whereas hydroxychloroquine does not appear to work in severely ill patients, perhaps it could be helpful earlier in the course of illness or in patients with less severe illness. This study enrolled 491 nonhospitalized patients with confirmed or probable COVID-19 who were enrolled online. More than half were enrolled within one day of symptom onset. A limitation of this study is that only 149 had a positive polymerase chain reaction (PCR) test, whereas 280 had a PCR positive contact to enter the study and 37 had neither but had typical symptoms. Patients were randomized to hydroxychloroquine 800 mg, followed by 600 mg six to eight hours later, and then 600 mg once daily for four additional days. They initially assumed a 10% hospitalization rate, but this did not happen, so they changed the primary outcome to the difference between groups in symptom severity over 14 days. The median age was 40 years, 56% were women, 32% had a comorbidity, and 3% were Black. They found no difference in overall symptom severity or the percentage with symptoms between groups. Adverse effects were twice as common in the treatment group (43% vs. 22%, p < 0.001), mostly gastrointestinal. The number of hospitalizations (12 total) and deaths (two) was small and did not differ between groups. The lack of diagnostic confirmation in most patients is concerning; however, a second study in Spain with 293 patients with confirmed infection published July 16, 2020, in
Clinical Infectious Diseases has similar results.
Written by Mark H. Ebell, MD, MS on July 17, 2020. (Source: Skipper CP, Pastick KA, Engen NW, et al. Hydroxychloroquine in nonhospitalized adults with early COVID-19: a randomized trial [published online July 16, 2020].
Ann Intern Med. 2020.
https://www.acpjournals.org/doi/10.7326/M20-4207(www.acpjournals.org))
https://www.aafp.org/journals/afp/explore/covid-19-daily-briefs.html
July 13, 2020, Research Update
Hydroxychloroquine Associated with Lower Mortality in Patients Hospitalized with COVID-19: Observational Study in Detroit. In this observational study from the Henry Ford Health System in Detroit, investigators examined the in-hospital mortality of 2,541 consecutive hospitalized COVID-19 patients in four treatment categories: hydroxychloroquine (HCQ) plus azithromycin (AZM), either drug alone, or neither drug. They excluded patients who died in the first 24 hours after admission and another 10% of patients for whom final outcome data were unavailable (e.g., still hospitalized, left against medical advice, or transferred to another facility). The median time to follow-up was 28.5 days. Overall in-hospital mortality was 18.1% (95% CI, 16.6% to 19.7%). Mortality for patients taking HCQ+AZM was 20.1% (95% CI, 17.3% to 23.0%); for HCQ alone, 13.5% (95% CI, 11.6% to 15.5%); for AZM alone, 22.4% (95% CI, 16.0% to 30.1%); and neither drug, 26.4% (95% CI, 22.2% to 31.0%). In the Cox regression analysis that adjusted for age, gender, comorbid conditions, and disease severity, the hazard ratio for mortality was reduced 66% (p < 0.001) compared with the group receiving neither HCQ nor AZM. The authors report wide variations in the use of corticosteroids among the different treatment groups: 36% in those treated with neither medication, 39% of those receiving AZM alone, 74% of those treated with both, and 79% of those receiving HCQ alone. This is an observational study. These kinds of studies can find associations but are fairly weak in determining a causal link between an exposure and an outcome. In this study, the findings are inconsistent with other observational studies and with data we have from the few randomized trials that exist. Additionally, they found no effect of steroids in the outcome, which is at odds with other studies (e.g., see Research Brief from June 30 on the effects of dexamethasone from the RECOVERY Collaborative Group), at least in those with severe COVID. Observational studies are subject to all kinds of bias and are subject to alternative explanations for the findings. For example, about 25% of the patients had missing measures of disease severity and were excluded from the regression model. The co-treatment with steroids is likely to reflect differences in disease severity. Observational studies are also unable to account for the “hidden” factors involved in how physicians decide the treatments they choose based on other patient characteristics. Finally, the regression analysis took into account only factors the authors chose and could not address residual confounding. In a randomized trial, the known and unknown factors associated with the outcome of interest are evenly distributed between the intervention groups.
Written by John Hickner, MD, MS, and Henry Barry, MD, MS, on July 7, 2020. (Source: Arshad S, Kilgore P, Chaudhry ZS, et al.; Henry Ford COVID-19 Task Force. Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19 [published online July 1, 2020].
Int J Infect Dis.
https://www.ijidonline.com/article/S1201-9712(20)30534-8/fulltext(www.ijidonline.com))
Click to expand...
