Table 4.

COVID-19 clinical trial results

Drug	COVID-19 clinical trial summary (NCT #)
ACE2 (recombinant human)	A two-part phase II trial comprising an open-label intrapatient dose escalation and a randomized, double-blind, placebo-controlled phase in intensive care units of COVID-19 patients found rhACE2 markedly reduced angiotensin II levels [169] (NCT01597635).
AZM	In a randomized clinical trial in Brazil, AZM used in combination with standard care, which included HCQ, did not result in a statistical difference in recovery time. Clinical trial did not note any significant increase between the control and AZM in arrhythmia, cardiac arrest, acute kidney failure, or QT interval prolongation [170] (NCT04321278).
Baricitinib	No clinical trials. Some cite baricitinib as a frequent cause of co-infection leading to increased mortality (PRAVEEN; PUVVADA; M, 2020). Link A double-blind, randomized, placebo-controlled clinical trial of baricitinib plus RDV was better than RDV alone in improving recovery time and clinical status of COVID-19 patients [171] (NCT04401579).
Colchicine	A prospective, open-label, randomized clinical trial of 105 patients in Greece noted significant clinical benefit of colchicine in COVID-19 hospitalized patients; however, there were no significant differences in cardiac troponin or CRP levels in the treated vs. control group [172] (NCT04326790).
Corticosteroids	Preliminary results of a clinical trial suggest hydrocortisone improved the time for patients to be organ support free; however, the trial was stopped early because no treatment strategy met prespecified criteria for statistical superiority, barring definitive conclusions. [173] (NCT02735707)
DEX	In a controlled, open-label trial, DEX reduced the 28-day mortality in hospitalized COVID-19 patients among those receiving invasive mechanical ventilation or oxygen but not in those without respiratory support [174] (NCT04381936). In a multicenter, randomized, open-label, 28-day clinical trial of intensive care units in Brazil of patients with COVID-19 and moderate to severe ARDS, DEX was effective at increasing the number of ventilator-free days in patients when used in conjunction with standard of care [175] (NCT04327401).
HCQ	In a multicenter, randomized, open-label, controlled trial of hospitalized patients with mild-to-moderate COVID-19 found the use of HCQ alone, or with AZM, did not improve clinical status at 15 days as compared with standard care [176] (NCT04322123). A randomized, double-blind, placebo-controlled clinical trial at 2 tertiary urban hospitals found no clinical benefit treating with HCQ daily for 8 weeks pre-exposure prophylaxis of health care workers [177] (NCT04329923). A randomized, double-blind, placebo-controlled clinical trial concluded that HCQ did not prevent illness after high-risk or moderate-risk exposure to COVID-19 as compared to the placebo group. Additionally, HCQ did not significantly reduce symptom severity in patients with early, mild COVID-19 [178] (NCT04308668). In a multicenter, blinded, placebo-controlled randomized clinical trial conducted at 34 hospitals in the USA of hospitalized adults, HCQ was not found to be effective at improving clinical status after 14 days as compared to placebo. Patients receiving HCQ had numerically higher but not statistically significant instances of adverse events compared to the placebo group [179] (NCT04332991).
Combination of IFNβ-1B, LPV, and ribavirin	A multicenter, prospective, open-label, randomized, phase 2 clinical trial of COVID-19 patients in six hospitals in Hong Kong treated with combination of IFNβ-1b, LPV–RTV, and ribavirin found the triple therapy to be statistically more effective at shortening hospital stay and viral shedding than just LPV–RTV for patients with mild-to-moderate COVID-19 [180] (NCT04276688).
Ivermectin	A pilot clinical trial of hospitalized patients with mild-to-moderate COVID-19 treated with the addition of ivermectin to HCQ and AZM had a shorter hospitalization period and no adverse effects Ivermectin therapy added to HCQ and AZT was more effective, shortening the length of the hospital stay, and with no obvious adverse events. However, the study was limited to a small number of patients [181] (NCT04343092).
LPV/RTV	A randomized, controlled, open-label, clinical trial did not find LPV/RTV successful in reducing duration of hospital stay, or mortality rate, or risk of progressing to invasive mechanical ventilation [182] (NCT04381936). In another randomized controlled trial, arbidol monotherapy treatment of mild-to-moderate COVID-19 patients did not significantly improve clinical outcome [183] (NCT04252885).
MP	A clinical trial of multicenter observation study exploring association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days found early administration of prolonged MP was associated with reduced hazard of death and ventilator dependence [184] (NCT04323592). A single pretest, single posttest quasi-experiment in a multicenter health system in Michigan found early short course of MP in moderate to severe COVID-19 patients may prevent disease progression and improve clinical outcomes [185] (NCT04374071). In a double-blind, placebo-controlled, randomized, phase IIb clinical trial in Brazil found short-term MP was not effective at reducing mortality rates. In the trial, patients meeting ARDS criteria were also treated intravenous with ceftriaxone plus AZM or clarithromycin. The trial did note that MP was significantly effective at reducing mortality rates in patients over the age of 60 [186] (NCT04343729).
RDV	A randomized, open-label, phase 3 trial of hospitalized severe COVID-19 patients with radiologic evidence of pneumonia not requiring mechanical ventilation treated with RDV did not show a significant difference between a 5- or 10-day treatment, and no placebo control was included [187] (NCT04292899). A randomized, open-label trial of hospitalized COVID-19 patients with confirmed severe ARDS did not find statistically significant clinical benefit with RDV as compared to standard care. Nausea, hypokalemia, and headache were more frequent in the RDV group [188] (NCT04292730). A double-blind, randomized, placebo-controlled trial of intravenous RDV in patients hospitalized with COVID-19 showed a significant difference in recovery time and reduced respiratory tract infection. More serious adverse events were reported for the placebo group than for the RDV group [189] (NCT04280705). A randomized, double-blind, placebo-controlled, multicenter trial at ten hospitals found RDV was not associated with a statistically significant difference in clinical benefits and was stopped due to more adverse events as compared to placebo [190] (NCT04257656).
Sarilumab	In an ongoing international, multifactorial trial, critically ill COVID-19 patients receiving organ support in intensive care treated with sarilumab (an IL-6 receptor antagonist) improved survival [191] (NCT02735707).
TCZ	A randomized controlled phase 3 COVACTA trial failed to meet its primary endpoint of improved clinical status and did not improve patient mortality, but TCZ-treated patients spent approximately a week less in hospital as compared with the placebo group. The broad eligibility criteria COVACTA did not appear to stratify patients by clinical signs of hyperinflammation, which could have an impact on the responsiveness of the patients to the drug [192] (NCT04320615). In a prospective, open-label, randomized clinical trial of hospitalized patients with COVID-19 pneumonia in Italy, TCZ was not found to be significantly better than the control standard care at preventing the patients from deteriorating [193] (NCT04346355). A randomized, double-blind, placebo-controlled trial of hospitalized COVID-19 patients found TCZ was not effective for preventing intubation or death in moderately ill patients [194] (NCT04356937). An ongoing international trial of critically ill COVID-19 patients receiving organ support in intensive care treated with TCZ improved survival [191] (NCT02735707).
Umifenovir (Arbidol hydrochloride)	In a randomized controlled trial, arbidol monotherapy treatment of mild-to-moderate COVID-19 patients did not significantly improve recovery time [183] (NCT04252885).