Ivermectin is an antiparasitic drug being investigated for repurposing against SARS-CoV-2. Ivermectin showed in-vitro activity against SARS-COV-2 at high concentrations. This meta-analysis investigated ivermectin in 24 randomized clinical trials (3328 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. Ivermectin was associated with reduced inflammatory markers (C-Reactive Protein, d-dimer and ferritin) and faster viral clearance by PCR. Viral clearance was treatment dose- and duration-dependent. In 11 randomized trials of moderate/severe infection, there was a 56% reduction in mortality (Relative Risk 0.44 [95%CI 0.25-0.77]; p=0.004; 35/1064 (3%) deaths on ivermectin; 93/1063 (9%) deaths in controls) with favorable clinical recovery and reduced hospitalization. Many studies included were not peer reviewed and a wide range of doses were evaluated. Currently, WHO recommends the use of ivermectin only inside clinical trials. A network of large clinical trials is in progress to validate the results seen to date.

Ivermectin is an antiparasitic drug being investigated for repurposing to SARS-CoV-2. In-vitro, ivermectin showed limited antiviral activity and a COVID-19 animal model demonstrated pathological benefits but no effect on viral RNA. This meta-analysis investigated ivermectin in 18 randomized clinical trials (2282 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. Ivermectin was associated with reduced inflammatory markers (C-Reactive Protein, d-dimer and ferritin) and faster viral clearance by PCR. Viral clearance was treatment dose- and duration-dependent. In six randomized trials of moderate or severe infection, there was a 75% reduction in mortality (Relative Risk=0.25 [95%CI 0.12-0.52]; p=0.0002); 14/650 (2.1%) deaths on ivermectin; 57/597 (9.5%) deaths in controls) with favorable clinical recovery and reduced hospitalization. Many studies included were not peer reviewed and meta-analyses are prone to confounding issues. Ivermectin should be validated in larger, appropriately controlled randomized trials before the results are sufficient for review by regulatory authorities.

BackgroundIvermectin which was widely considered as a potential treatment for COVID-19, showed uncertain clinical benefit in many clinical trials. Performing large-scale clinical trials to evaluate the effectiveness of this drug in the midst of the pandemic, while difficult, has been urgently needed.MethodsWe performed two large multicenter randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of ivermectin in treating inpatients and outpatients with COVID-19 infection. The intervention group received ivermectin, 0.4mg/kg of body weight per day for 3 days. In the control group, placebo tablets were used for 3 days.ResultsData for 609 inpatients and 549 outpatients were analyzed. In hospitalized patients, complete recovery was significantly higher in the ivermectin group (37%) compared to placebo group (28%; RR, 1.32 [95% CI, 1.04–1.66]; p-value = 0.02). On the other hand, the length of hospital stay was significantly longer in the ivermectin group with a mean of 7.98 ± 4.4 days compared to the placebo receiving group with a mean of 7.16 ± 3.2 days (RR, 0.80 [95% CI, 0.15–1.45]; p-value = 0.02). In outpatients, the mean duration of fever was significantly shorter (2.02 ± 0.11 days) in the ivermectin group versus (2.41 ± 0.13 days) placebo group with p value = 0.020. On the day seventh of treatment, fever (p-value = 0.040), cough (p-value = 0.019), and weakness (p-value = 0.002) were significantly higher in the placebo group compared to the ivermectin group. Among all outpatients, 7% in ivermectin group and 5% in placebo group needed to be hospitalized (RR, 1.36 [95% CI, 0.65–2.84]; p-value = 0.41). Also, the result of RT-PCR on day five after treatment was negative for 26% of patients in the ivermectin group versus 32% in the placebo group (RR, 0.81 [95% CI, 0.60–1.09]; p-value = 0.16).ConclusionOur data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients; likewise, no evidence was found to support the prescription of ivermectin on recovery, reduced hospitalization and increased negative RT-PCR assay for SARS-CoV-2 5 days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19.Clinical Trial Registrationwww.irct.ir IRCT20111224008507N5 and IRCT20111224008507N4.

Background Currently, only dexamethasone, tocilizumab and sarilumab have conclusively been shown to reduce mortality of COVID-19. Safe and effective treatments will need to be both affordable and widely available globally to be used alongside vaccination programmes. This analysis will estimate and compare potential generic minimum costs of a selection of approved COVID-19 drug candidates with available international list prices. Methods We searched for repurposed drugs that have been approved by at least one of the WHO, FDA or NICE, or at least given emergency use authorisation or recommended for off-label prescription. Drug prices were searched for, for dexamethasone, budesonide, baricitinib, tocilizumab, casirivimab and imdevimab, and sarilumab using active pharmaceutical ingredients (API) data extracted from global shipping records. This was compared with national pricing data from a range of low, medium, and high-income countries. Annual API export volumes from India were used to estimate the current availability of each drug. Results Repurposed therapies can be generically manufactured for some treatments at very low per-course costs, ranging from $2.58 for IV dexamethasone (or $0.19 orally) and $4.34 for inhaled budesonide. No export price data was available for baricitinib, tocilizumab, casirivimab and imdevimab or sarilumab, but courses of these treatments are priced highly, ranging from $6.67 for baricitinib to $875.5 for sarilumab. When comparing international list prices, we found wide variations between countries. Conclusions Successful management of COVID-19 will require equitable access to treatment for all populations, not just those able to pay high prices. Dexamethasone and budesonide are widely available and affordable, whilst monoclonal antibodies and IV treatment courses are more expensive.

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