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Outlook and Recommendations
428 | CovidReference.com
Ivermectin
Ivermectin, an inexpensive, over-the-counter medicine, is widely used as a preventative against COVID-19 in many South & Latin American countries. However, the evidence that ivermectin protects from COVID-19 is scant. A group from Bangladesh conducted a randomized, double-blind, placebocontrolled trial of oral ivermectin alone or in combination with doxycycline compared with placebo among 72 hospitalized patients. Virological clearance was earlier in the 5-day ivermectin treatment arm vs the placebo group (9.7 days vs 12.7 days; p = 0.02); but not in the ivermectin + doxycycline arm (11.5 days; p = 0.27) (Ahmed 2020). There were no severe adverse drug events recorded in the study. According to the authors, “larger trials will be needed to confirm these preliminary findings”.
Other treatments with no effects
Azithromycin
Azithromycin as a macrolide antibiotic has probably no effect against SARSCoV-2 (see the many studies above, testing it in combination with HCQ). In a large RCT conducted at 57 centers in Brazil, 214 patients who needed oxygen supplementation of more than 4 L/min flow, high-flow nasal cannula, or mechanical ventilation (non-invasive or invasive) were assigned to the azithromycin group and 183 to the control group. Azithromycin had no effect (Furtado 2020).
Leflunomide
Leflunomide (Arava®) is an approved antagonist of dihydroorotate dehydrogenase, has some antiviral and anti-inflammatory effects and has been widely used to treat patients with autoimmune diseases. In a small RCT from Wuhan on 50 COVID-19 patients with prolonged PCR positivity, no benefit in terms of the duration of viral shedding was observed with the combined treatment of leflunomide and IFN α-2a vs IFN α-2a alone (Wang 2020).
N-acetylcysteine
N-acetylcysteine had no effect, even at high-doses (De Alencar 2020). In an RCT from Brazil of 135 patients with severe COVID-19, 16 patients (24%) in the placebo group were submitted to endotracheal intubation and mechanical ventilation, compared to 14 patients (21%) in the NAC group (p = 0.675). No difference was observed on secondary endpoints.