Latest:
- GlaxoSmithKline announced results from the phase II proof of concept OSCAR study with otilimab which showed that in patients of all ages treatment difference was not statistically significant between the otilimab and standard of care groups, but in analysis by age, patients 70 years and older had an increased chance of being alive and free of respiratory failure 28 days after treatment with otilimab compared to the standard care group (65.1% vs 45.9%);
- Published results from the REMAP-CAP trial in New England Journal of Medicine (NEJM) show that in critically ill patients with COVID-19 receiving organ support in ICUs, treatment with the IL-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival (REMAP-CAP Investigators, 25 February 2021);
- Results from the COVACTA trial in NEJM showed that in hospitalised patients with severe COVID-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days (Rosas et al, 25 February 2021).

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Researchers around the world are working at record speed to find the best ways to treat and prevent COVID-19, from investigating the possibility of repurposing existing drugs to searching for novel therapies against the virus.
Current approaches to COVID-19 therapies generally fall into two categories: antivirals — which prevent the virus from multiplying — and immune modulators — which help the immune system to fight the virus or stop it from overreacting dangerously. Some potential therapies act in a different way or via multiple mechanisms.
There are thousands of clinical trials of COVID-19 therapies taking place across the world. On 15 June 2020, the European Medicines Agency said it was in discussion with the developers of 132 potential COVID-19 treatments[1].
This article collates the main treatments being studied, the evidence supporting their use and the trials they are being evaluated in. It will be updated on a regular basis.
Only evidence from randomised controlled trials comprising more than 100 participants is included, with the exception of select observational studies that have had a significant influence on ongoing research.
Contents
- Remdesivir
- Chloroquine/hydroxychloroquine
- Lopinavir/ritonavir combination
- Favipiravir
- Umifenovir
- Ribavirin
- EIDD-2801
- Niclosamide
- Oseltamivir
- Ivermectin
Immune modulators:
- Dexamethasone
- Hydrocortisone
- Convalescent plasma
- Budesonide (inhaled)
- AZD7442
- Azithromycin
- Doxycycline
- Interferons
- Tocilizumab
- Sarilumab
- Canakinumab
- Anakinra
- Baricitinib
- Ruxolitinib
- Acalabrutinib
- Brensocatib
- Ravulizumab
- Gemtuzumab ozogamicin
- Namilumab
- Infliximab
- Adalimumab
- Otilimab
- Medi3506
- Antiviral antibody cocktail
- Leronlimab
- LY-CoV555
- LY-CoV016
- Risankizumab
- Lenzilumab
- IMU-838
Other or multiple mechanisms:
- Colchicine
- Angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers
- Statins
- Aspirin
- Clopidogrel
- Anticoagulants
- Bemcentinib
- Omeprazole
- Famotidine
- Zilucoplan
- Ascorbic acid/vitamin C
- Aviptadil
- Opaganib
- Tradipitant
- AZD1656
- Nitric oxide
- Razuprotafib
- Fluvoxamine
Antivirals

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Remdesivir
- Broad-spectrum antiviral originally developed to treat hepatitis C and was then tested against Ebola;
- In vitro activity against SAR-CoV-2;
- Some evidence of efficacy against COVID-19 in humans;
- Available on a ‘compassionate use’ basis in many countries;
- First COVID-19 treatment to be made available for use in the UK outside a clinical trial;
- In the EU, remdesivir is now licensed for the treatment of COVID-19 in adults and adolescents with pneumonia requiring supplemental oxygen;
- On 20 November 2020, the WHO issued a conditional recommendation against the use of remdesivir in hospitalised patients, regardless of disease severity, as there is currently no evidence that remdesivir improves survival and other outcomes in these patients.
Evidence
- Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with COVID-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events (Kalil et al, 11 December 2020);
- Interim results from the Solidarity trial suggest that remdesivir has little or no effect on mortality in patients who are hospitalised with COVID-19 (WHO Solidarity Trial Consortium, 2 December 2020);
- Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalised with COVID-19 and had evidence of lower respiratory tract infection (Beigel et al, 8 October 2020)
- In moderate COVID-19, a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance (Spinner et al, 21 August 2020)
- No significant efficacy difference between five and ten day courses of remdesivir in patients with severe COVID-19 (Goldman et al, 27 May 2020);
- “No statistically significant differences” for mortality and serious adverse events in COVID-19 patients treated with remdesivir (National Institute for health and Care Excellence [NICE]);
- First randomised trial of remdesivir suggests antiviral drug is not associated with significant clinical benefits, but numerical reduction in time to clinical improvement suggests more research needed (Wang et al, 29 April 2020).
Ongoing trials
- Adaptive COVID-19 treatment trial (ACTT);
- Adaptive COVID-19 treatment trial 2 (ACTT-II);
- Trial of Treatments for COVID-19 in Hospitalized Adults (DISCOVERY);
- Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734) in Participants With Severe Coronavirus Disease (COVID-19);
- Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734) in Participants With Moderate Coronavirus Disease (COVID-19) Compared to Standard of Care Treatment;
- SOLIDARITY clinical trial for COVID-19 treatments;
- Phase III trial to investigate combination of tocilizumab and remdesivir in severe COVID-19 pneumonia (REMDACTA).
Chloroquine/hydroxychloroquine
- Antimalarials with in vitro activity against various viruses, including SAR-CoV-2 — the virus that causes COVID-19;
- Anecdotal evidence in humans;
- The US Food and Drug Administration has cautioned against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems;
- In June 2020, all UK clinical trials using hydroxychloroquine to treat or prevent COVID-19 were instructed by the Medicines and Healthcare products Regulatory Agency (MHRA) to stop recruiting further participants;
- Approved for the treatment of rheumatoid arthritis and lupus.
Evidence
- Rigorous randomised controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection (Barnabas et al, 8 December 2020);
- Interim results from the Solidarity trial suggest that remdesivir has little or no effect on mortality in patients who are hospitalised with COVID-19 (WHO Solidarity Trial Consortium, 2 December 2020);
- Post-exposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic COVID-19 in healthy persons exposed to a PCR-positive case patient (Mitjà et al. 24 November 2020);
- Among adults hospitalised with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14 (Self et al, 9 November 2020);
- Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed COVID-19 or COVID-19-compatible illness among healthcare workers (Rajasingham et al, 17 October 2020);
- Among patients hospitalised with COVID-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care (The RECOVERY collaborative group, 8 October 2020);
- Among hospital-based health care workers, daily hydroxychloroquine did not prevent SARS-CoV-2 infection, although the trial was terminated early and may have been underpowered to detect a clinically important difference (Abella et al, 30 September 2020)
- Among patients hospitalised with mild-to-moderate COVID-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care (Cavalcanti et al, 23 July 2020)
- Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19 (Skipper et al, 16 July 2020)
- UK Medicines and Healthcare products Regulatory Agency (MHRA) suspends recruitment to COVID-19 hydroxychloroquine trials (5 June 2020)
- Preliminary results from ‘Randomised Evaluation of COVID-19 Therapy’ (RECOVERY) trial (5 June 2020): no significant difference in mortality rate at 28 days (25.7% hydroxychloroquine vs. 23.5% usual care; hazard ratio 1.11 [95% confidence interval 0.98–1.26]; P =0.10);
- Hydroxychloroquine did not prevent illness compatible with COVID-19 or confirmed infection when used as postexposure prophylaxis within four days after exposure (Boulware et al, 3 June 2020);
- No evidence of benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias (Mehra et al, 22 May 2020). Study retracted by The Lancet on 5 June 2020 following concerns about the data;
- Not enough data available to support the routine use of hydroxychloroquine and chloroquine as therapies for COVID-19 (Chowdhury et al, 29 May 2020);
- Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone (Tang et al, 14 May 2020).
Ongoing trials
- RECOVERY trial (recruitment to hydroxychloroquine arm closed as of 5 June 2020);
- Chemoprophylaxis for COVID-19 infectious disease (the PROLIFIC trial);
- An adaptive phase 2/3, randomised, open-label study assessing efficacy and safety of hydroxychloroquine for hospitalised patients with moderate to severe COVID-19;
- ‘Randomised, Embedded, Multifactorial, Adaptive Platform trial for Community-Acquired Pneumonia’ [REMAP-CAP] (paused by MHRA as of June 2020);
- ‘Platform Randomised trial of Interventions against COVID-19 In Older People’ [PRINCIPLE] (paused by MHRA as of June 2020);
- ‘Chloroquine Prevention of Coronavirus Disease (COVID-19) in the Healthcare Setting’; a randomised, placebo-controlled prophylaxis study (COPCOV) (given green light by MHRA to continue recruiting patients on 26 June 2020);
- ‘(Hydroxy)chloroquine Repurposing to Healthworkers for Novel Coronavirus Mitigation: An international, multi-site, Bayesian platform adaptive, randomised, double-blind, placebo-controlled trial assessing the effectiveness of varied doses of oral chloroquine’ (CROWN CORONATION);
- Prophylaxis for patients at risk of COVID-19 infection (PROTECT);
- SOLIDARITY (recruitment to hydroxychloroquine arm closed as of 17 June 2020);
- DISCOVERY;
- Hydroxychloroquine or Diltiazem-Niclosamide for the Treatment of COVID-19 (HYDILIC);
- Health Care Worker Prophylaxis Against COVID-19 (HERO).
Lopinavir/ritonavir combination
- HIV type 1 aspartate protease inhibitors, indicated for treatment of HIV infection in combination with other antiretroviral drugs;
- Lopinavir has in vitro inhibitory activity against SARS-CoV, the virus that causes severe acute respiratory syndrome (SARS);
- Ritonavir is combined with lopinavir to increase its half-life;
- Recommended for use in COVID-19 in several countries, including Italy and France.
Evidence
- Interim results from the Solidarity trial suggest that remdesivir has little or no effect on mortality in patients who are hospitalised with COVID-19 (WHO Solidarity Trial Consortium, 2 December 2020);
- In patients admitted to hospital with COVID-19, lopinavir–ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death (The RECOVERY collaborative group, 5 October 2020).
- Following a review of emerging data from the RECOVERY trial, researchers concluded that there was no beneficial effect of lopinavir/ritonavir on 28-day mortality in patients hospitalised with COVID-19 compared to usual care alone (Horby et al, 29 June 2020);
- Evidence that early treatment with triple antiviral therapy of interferon (IFN) beta-1b, lopinavir/ritonavir, and ribavirin — alongside standard care — is safe and shortens duration of viral shedding compared with lopinavir-ritonavir alone (average 7 days vs. 12 days), in patients with mild-to-moderate COVID-19 (Hung et al, 8 May 2020);
- Some evidence that lopinavir/ritonavir initiation within 12 days after symptom onset is associated with shorter time to clinical improvement. No significant differences in reduction of viral RNA load, duration of viral RNA detectability, duration of oxygen therapy, duration of hospitalisation, or time from randomization to death. Lopinavir/ritonavir stopped early in 13 patients because of adverse effects (Cao et al, 7 May 2020).
Ongoing trials
- REMAP-CAP;
- RECOVERY (recruitment to lopinavir/ritonavir arm closed as of 29 June 2020);
- SOLIDARITY (recruitment to lopinavir/ritonavir arm closed as of 4 July 2020);
- DISCOVERY;
- Lopinavir/ Ritonavir, Ribavirin and IFN-beta Combination for nCoV Treatment.
Favipiravir
- Broad-spectrum antiviral with in vitro activity against various viruses, including coronaviruses;
- Licensed in Japan and China for treatment of influenza;
- Not currently included in any of the UK trials for COVID-19.
Ongoing trials
- Phase III Clinical Study to Evaluate the Performance and Safety of Favipiravir in COVID-19;
- Oral Favipiravir Compared to Placebo in Subjects with Mild COVID-19;
- A Randomized Controlled Trial for Favipiravir Tablets Combine with Chloroquine Phosphate in the Treatment of Novel Coronavirus Pneumonia (COVID-19);
- Favipiravir Combined with Tocilizumab in the Treatment of novel coronavirus pneumonia (COVID-19) — a multicentre, randomised, controlled trial;
- The Efficacy and Safety of Favipiravir for novel coronavirus–infected pneumonia — a multicentre, randomised, open, positive, parallel-controlled clinical study.
Umifenovir
- Antiviral treatment used for influenza infection in Russia and China;
- Proposed as a standard care option for COVID-19 based on its mechanism of action and its effects in treating influenza-associated pneumonia;
- In vitro inhibitory activity against SARS-CoV, the virus that causes severe acute respiratory syndrome (SARS)
Ongoing trials:
Ribavirin
- Broad-spectrum antiviral used to treat hepatitis C, respiratory syncytial virus (RSV) and bronchiolitis;
- In vitro activity against SARS-CoV, the virus that causes severe acute respiratory syndrome (SARS);
- Some evidence of efficacy as an adjunct therapy in SARS;
- Evidence from mouse models in SARS-CoV suggested it could increase infectivity.
Evidence
- Evidence that early treatment with triple antiviral therapy of IFN beta-1b, lopinavir-ritonavir, and ribavirin — alongside standard care — is safe and shortens duration of viral shedding compared with lopinavir-ritonavir alone (average 7 days vs. 12 days), in patients with mild to moderate COVID-19 (Hung et al, 8 May 2020).
EIDD-2801
- Investigational oral nucleoside analogue with broad-spectrum antiviral activity against RNA viruses, including influenza and coronaviruses like SARS and Middle East respiratory syndrome (MERS).
Ongoing trials
Niclosamide
- Anti-helminthic drug with potential antiviral activity against SARS-CoV-2;
- Unlicensed in the UK.
Ongoing trials
- HYDILIC;
- Niclosamide for mild-to-moderate COVID-19 (Not yet recruiting).
Oseltamivir
- A neuraminidase inhibitor approved for the treatment of influenza A and B;
- Several clinical trials are evaluating the effectiveness of oseltamivir in treating SARS-CoV-2 both alone and in combination with other drugs.
Ongoing trials
- IMU-838 and Oseltamivir in the Treatment of COVID-19 (IONIC);
- Hydroxychloroquine, Oseltamivir and Azithromycin for the Treatment of COVID-19 Infection: An RCT (PROTECT);
- Favipiravir, Protease Inhibitors, Oseltamivir -Gpo, Hydroxychloroquine for Treatment of COVID-19 (FIGHT-COVID-19);
- A Prospective/Retrospective,Randomized Controlled Clinical Study of Antiviral Therapy in the 2019-nCoV Pneumonia
Ivermectin
- Anti-parasitic agent shown to have antiviral activity against a broad range of viruses;
- Unlicensed in the UK;
- Shown to inhibit the SARS-CoV-2 virus in vitro.
Ongoing trials
- Ivermectin in Adults With Severe COVID-19;
- Outpatient Use of Ivermectin in COVID-19;
- Ivermectin to Prevent Hospitalizations in COVID-19 (IVERCORCOVID19);
- Efficacy and Safety of Ivermectin for Treatment and Prophylaxis of COVID-19 Pandemic;
- Efficacy of Ivermectin in Adult Patients With Early Stages of COVID-19 (EPIC Trial) (EPIC).
Immune modulators

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Dexamethasone
- Steroid that reduces inflammation by mimicking anti-inflammatory hormones produced by the body;
- Indicated for the suppression of inflammatory and allergic disorders;
- Only suitable for people who are already in hospital and receiving oxygen or mechanical ventilation;
- It is the first drug to be shown to improve survival in COVID-19;
- Approved for NHS use by UK government.
Evidence
- Intravenous dexamethasone plus standard care, compared with standard of care alone, resulted in a statistically significant increase in the number of days alive and free of mechanical ventilation over 28 days. (Tomazini et al, 2 September 2020);
- Preliminary results from the RECOVERY trial suggest that dexamethasone reduced deaths by 35% in ventilated patients and by 20% in other patients receiving oxygen only. There was no benefit among those patients who did not require respiratory support (Horby et al, 17 July 2020).
Ongoing trials
- RECOVERY;
- REMAP-CAP.
Hydrocortisone
- Steroid that reduces inflammation by mimicking anti-inflammatory hormones produced by the body;
- Used for a variety of conditions including adrenocortical insufficiency, rheumatoid arthritis, dermatitis, asthma and chronic obstructive pulmonary disorder;
- Commonly used to manage septic shock in patients with COVID-19;
- Evidence regarding corticosteroid use for severe COVID-19 is limited.
Evidence
- Patients with severe COVID-19 who are treated intravenously with the steroid, hydrocorticosone, are up to 93% more likely to have a better outcome compared to patients who are not given the drug, principal findings from the REMAP-CAP trial suggest. However, the trial was stopped early and no treatment strategy met pre-specified criteria for statistical superiority (Angus et al, 2 September 2020);
- Low-dose hydrocortisone did not significantly reduce treatment failure in patients with COVID-19–related acute respiratory failure; however, the study was stopped early and was therefore likely underpowered (Dequin et al, 2 September 2020).
Ongoing trials
Budesonide (inhaled)
- Inhaled budesonide is often used to treat asthma and chronic obstructive pulmonary disease, with no serious side-effects associated with short-term use;
- In some patients with COVID-19, the body’s immune response to the virus can cause high levels of inflammation that can damage cells in the airways and lungs. Inhaling budesonide into the airways targets anti-inflammatory treatment where it is needed most, and can potentially minimise any lung damage that might otherwise be caused by the virus.
Ongoing trials
- PRINCIPLE;
- STerOids in COVID-19 Study (STOIC);
- Trial Evaluating the Efficacy of Local Budesonide Therapy in the Management of Hyposmia in COVID-19 Patients Without Signs of Severity (COVIDORL);
- Inhaled Corticosteroid Treatment of COVID-19 Patients With Pneumonia;
- Protective Role of Inhaled Steroids for COVID-19 Infection (INHASCO)
Convalescent plasma
- Antibody-rich plasma of someone who has recovered from COVID-19;
- There is some evidence suggesting possible benefits of convalescent plasma in patients with COVID-19, but available data to date are largely from case reports or series; confirmation from additional randomised controlled studies is required (Malani et al, 12 June 2020);
- Has been approved for use in critically ill patients in the United States and UK.
Evidence
- Convalescent plasma has no benefit for patients with COVID-19 who are severely ill and in intensive care, according to early findings from the ‘Randomised, Embedded, Multifactorial, Adaptive Platform trial for Community-Acquired Pneumonia’ (REMAP-CAP) trial (12 January 2021);
- Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of COVID-19 (Libster et al, 6 January 2021);
- No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo (Simonovich et al. 24 November 2020);
- No difference in 28 day mortality or progression to severe disease among patients with moderate COVID-19 treated with convalescent plasma along with best standard of care compared with best standard of care alone (Agarwal et al, 22 October 2020);
- No significant difference in time to clinical improvement within 28 days, mortality or time to hospital discharge in patients treated with convalescent plasma. Trial was terminated early and may have been underpowered to detect a clinically important difference (Li et al, 3 June 2020).
Ongoing trials
- RECOVERY;
- ‘Convalescent Plasma for Hospitalised Adults With COVID-19 Respiratory Illness’ (CONCOR-1);
- REMAP-CAP;
- Convalescent Plasma to Limit COVID-19 Complications in Hospitalized Patients(CONTAIN COVID-19);
- Passive Immunity Trial Of the Nation for COVID-19 (PassItOnII).
AZD7442
- AZD7442 is a combination of two long-acting antibodies (LAABs) derived from convalescent patients after SARS-CoV-2 infection;
- LAABs mimic natural antibodies and have the potential to treat and prevent disease progression in patients already infected with the virus, as well as to be given as a preventative intervention prior to exposure to the virus;
- In pre-clinical experiments the two LAABs have been shown to block the binding of the SARS-CoV-2 virus to host cells and protect against infection in cell and animal models of disease.
Ongoing trials
- Phase III Double-blind, Placebo-controlled Study of AZD7442 for Post- Exposure Prophylaxis of COVID-19 in Adults (STORM CHASER);
- Phase III Double-blind, Placebo-controlled Study of AZD7442 for Pre-exposure Prophylaxis of COVID-19 in Adult. (PROVENT)
Azithromycin
- Macrolide antibiotic;
- Some in vitro activity against some viruses, such as influenza A and zika;
- May reduce cytokine levels, which can promote inflammation.
Evidence
- Azithromycin should not be used in the management of confirmed or suspected COVID-19, the Department of Health and Social Care has advised (1 February 2021);
- Preliminary analysis of data from the RECOVERY trial has revealed that there was no significant difference in the primary endpoint of 28-day mortality between azithromycin (19%) and usual care (19%). There was also no evidence of beneficial effects on the risk of progression to mechanical ventilation or length of hospital stay (14 December 2020);
- In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes (Furtado et al, 4 September 2020);
- Among patients hospitalized with mild-to-moderate COVID-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care (Cavalcanti et al, 23 July 2020).
Ongoing trials
- RECOVERY;
- PRINCIPLE.
Doxycycline
- A broad-spectrum tetracycline-class antibiotic used in the treatment of infections caused by bacteria and certain parasites;
- Considered as a potential treatments for COVID-19 in the community due to its anti-inflammatory, antibacterial and possibly antiviral effects;
- It has been reported that doxycycline lowers significantly proinflammatory cytokines, including interleukin-6.
Evidence
- Doxycycline should not be used in the management of confirmed or suspected COVID-19, the Department of Health and Social Care has advised (1 February 2021);
- Interim analyses of data from the doxycycline arm of the PRINCIPLE trialconcluded that there was no beneficial effect in patients aged over 50 who are treated with doxycycline at home in the early stages of COVID-19. The researchers also found that the treatment did not reduce the time taken for people to first report that they feel recovered from COVID-19.
Ongoing trials
- PRINCIPLE;
- Doxycycline Ambulatoire COVID-19 (DYNAMIC);
- Clinical Trial of Ivermectin Plus Doxycycline for the Treatment of Confirmed Covid-19 Infection;
- Safety and Efficacy of Doxycycline and Rivaroxaban in COVID-19 (DOXYCOV).
Interferons
- Modulate immune response to some viral infections;
- Only limited clinical trial data are currently available on the efficacy of IFNs for treatment of COVID-19;
- Clinical trials are currently evaluating IFN beta-1a or IFN beta-1b, generally added to antivirals.
Evidence
- Interim results from the Solidarity trial suggest that IFN beta-1a has little or no effect on mortality in patients who are hospitalised with COVID-19 (15 October 2020).
Ongoing trials
- REMAP-CAP;
- Comparing efficacy and safety of inhaled SNG001 to placebo;
- SOLIDARITY;
- DISCOVERY;
- RECOVERY.
Tocilizumab
- Monoclonal antibody that inhibits interleukin-6 (IL-6), which is vital in the immune response to SAR-CoV-2;
- Indicated for treatment of rheumatoid arthritis;
- May combat cytokine release syndrome in severely ill COVID-19 patients.
Evidence
- Published results from the REMAP-CAP trial in New England Journal of Medicine (NEJM) show that in critically ill patients with COVID-19 receiving organ support in ICUs, treatment with the IL-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival (REMAP-CAP Investigators, 25 February 2021);
- Results from the COVACTA trial in NEJM showed that in hospitalised patients with severe COVID-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days (Rosas et al, 25 February 2021).
- Preliminary results from the RECOVERY trial suggest that for every 25 patients treated with tocilizumab, one additional life would be saved, and for patients who were not on invasive mechanical ventilation, tocilizumab also significantly reduced the chance of progressing to invasive mechanical ventilation or death from 38% to 33% (11 February 2021);
- A randomised controlled trial has found that, in patients with severe or critical COVID-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days and might increase mortality (Veiga et al, 20 January 2021);
- Early results from the REMAP-CAP trial suggest that the mortality rate was 35.8% for patients receiving the current standard of care alone and 27.3%, on average, for patients given tocilizumab or sarilumab; (28.0% for tocilizumab, 22.2% for sarilumab) and NHS guidance has been updated to recommend both drugs are considered in the treatment of COVID-19 patients admitted to intensive care (7 January 2021);
- In hospitalised patients with COVID-19 pneumonia who were not receiving mechanical ventilation, tocilizumab reduced the likelihood of progression to the composite outcome of mechanical ventilation or death, but it did not improve survival. No new safety signals were identified (Salama et al. 17 December 2020);
- Early findings from the REMAP-CAP trial have suggested that tocilizumab significantly improves outcomes for critically ill patients with severe COVID-19, potentially reducing mortality and time spent in intensive care (19 November 2020);
- Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalised patients with COVID-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide (Stone et al, 21 October 2020);
- Tocilizumab may reduce the need for mechanical and noninvasive ventilation or death by day 14 but not mortality by day 28 (Hermine et al, 20 October 2020);
- For hospitalised adult patients with COVID-19 pneumonia and partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio of between 200-300mmHg, tocilizumab had no benefit on disease progression compared with standard care (Salvarani et al, 20 October 2020);
- Patients who received tocilizumab were 44% less likely to progress to mechanical ventilation or death compared to patients who received placebo plus standard of care according to late-stage clinical data (18 September 2020).
Ongoing trials
- ‘A Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients with Severe COVID-19 Pneumonia’ (COVACTA);
- REMAP-CAP;
- RECOVERY;
- A randomised, double-blind, placebo-controlled multicentre study to evaluate the safety and efficacy of tocilizumab in patients with severe COVID-19 pneumonia;
- ‘Tocilizumab in COVID-19 Pneumonia’ (TOCIVID-19);
- Phase III clinical trial, part of a global effort, to assess whether tocilizumab might have therapeutic value for COVID-19 patients who have developed or at high risk of developing serious lung damage from SARS-CoV-2 infections.
Sarilumab
- Monoclonal antibody that inhibits IL-6, which is vital in the immune response to SAR-CoV-2;
- Indicated for treatment of rheumatoid arthritis;
- May combat cytokine release syndrome and pulmonary symptoms in severely ill COVID-19 patients.
Evidence
- Published results from the REMAP-CAP trial in New England Journal of Medicine show that in critically ill patients with COVID-19 receiving organ support in ICUs, treatment with the IL-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival (REMAP-CAP Investigators, 25 February 2021);
- Early results from the REMAP-CAP trial suggest that the mortality rate was 35.8% for patients receiving the current standard of care alone and 27.3%, on average, for patients given tocilizumab or sarilumab; (28.0% for tocilizumab, 22.2% for sarilumab) and NHS guidance has been updated to recommend both drugs are considered in the treatment of COVID-19 patients admitted to intensive care (7 January 2021);
- Sarilumab (Kevzara) demonstrates mixed efficacy results in ongoing COVID-19 trial of hospitalised patients with severe or critical respiratory illness secondary to COVID-19 (27 April 2020);
- Sarilumab fails to meet its primary and key secondary endpoints in US COVID-19 patients requiring mechanical ventilation. Minor positive trends were demonstrated in the primary pre-specified analysis group, but the results did not achieve statistical significance (2 July 2020).
Ongoing trials
- REMAP-CAP;
- Evaluation of the efficacy and safety of sarilumab in hospitalised patients with COVID-19.
Canakinumab
- Inhibits interleukin-1 (IL-1), which is vital in the immune response to SAR-CoV-2;
- Indicated to treat certain periodic fever syndromes and gouty arthritis;
- Potential to treat cytokine release syndrome in severely ill COVID-19 patients.
Evidence
- An interim analysis of the CAN-COVID trial showed the drug did not meet the primary endpoint of clinical response, defined as survival without the need for mechanical ventilation up to day 29. The drug also failed on a key secondary endpoint, reduction in COVID-19-related death within four weeks after the treatment period.
Ongoing trials
Anakinra
- Inhibits IL-1, which is vital in the immune response to SAR-CoV-2;
- Indicated for treatment of rheumatoid arthritis, Still’s disease and cryopyrin-associated periodic syndromes;
- Might help to neutralise the cause of acute respiratory distress syndrome (ARDS) among patients with COVID-19;
- Anakinra has been used (off label) for cytokine storm syndromes triggered by other viruses and is reported to be relatively well tolerated, with a favourable safety profile.
Evidence
- Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19 (The CORIMUNO-19 collaborative group, 22 January 2021).
Ongoing trials
- REMAP-CAP.
Baricitinib
- Janus-associated tyrosine kinase (JAK) 1 and JAK 2 inhibitor;
- Modulates the immune response by regulating overactive signalling through the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway;
- Indicated for treatment of rheumatoid arthritis;
- May potentially combat cytokine release syndrome (CRS) in severely ill patients;
- Currently no known published controlled clinical trial evidence supporting efficacy or safety in patients with COVID-19.
Evidence
- Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with COVID-19, notably among those receiving high-flow oxygen or non-invasive ventilation. The combination was associated with fewer serious adverse events (Kalil et al, 11 December 2020).
Ongoing trials
- RECOVERY (2 February 2021);
- Multi-arm Therapeutic study in Pre-ICU Patients Admitted with COVID-19-Repurposed Drugs (TACTIC-R);
- ACTT-II;
- Phase III, randomized, double-blind, placebo-controlled study (COLCORONA);
- A Study of Baricitinib (LY3009104) in Participants With COVID-19 (COV-BARRIER).
Ruxolitinib
- Selective inhibitor of JAK 1 and JAK 2;
- Modulates the immune response by regulating overactive signalling through the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway;
- Indicated for specialist treatments;
- May combat CRS in severely ill patients;
- Currently no known published clinical trial evidence supporting efficacy or safety in patients with COVID-19.
Evidence
- RUXCOVID trial found that ruxolitinib on top of standard therapy showed no significant reduction in severe complications of COVID-19, including death, respiratory failure requiring mechanical ventilation or admission to the intensive care unit. There was also no relevant benefit for other endpoints including mortality rate by day 29 and time to recovery.
Ongoing trials
- ‘Phase III Randomised, Double-Blind, Placebo-Controlled Multicentre Study to Assess the Efficacy and Safety of Ruxolitinib in Patients with COVID-19-Associated Cytokine Storm’ (RUXCOVID);
- ‘Assessment of Efficacy and Safety of Ruxolitinib in Participants with COVID-19-Associated ARDS who Require Mechanical Ventilation’ (RUXCOVID-DEVENT).
Acalabrutinib
- Bruton’s tyrosine kinase inhibitor;
- In clinical development for people with chronic lymphocytic leukaemia, approved for this use in the United States;
- Early clinical data have shown it can lead to a decrease in inflammation and reduction in the severity of COVID-19-induced respiratory distress.
Evidence
Ongoing trials
- ‘A Multicentre, Seamless, Phase II Adaptive Randomisation Platform Study to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID 19 in Hospitalised Patients’ (ACCORD);
- ‘Acalabrutinib Study with Best Supportive Care versus Best Supportive Care in Subjects Hospitalised with COVID-19’ (CALAVI).
Brensocatib
- Reversible inhibitor of the dipeptidyl peptidase-1 enzyme, which is known to be associated with pathogen destruction and inflammatory mediation;
- Not licensed in the UK;
- Could be beneficial for ARDS in severely ill COVID-19 patients.
Ongoing trials
Ravulizumab
- Recombinant monoclonal antibody;
- Used routinely in blood diseases where complement activation destroys red blood cells;
- Potential to treat CRS in severely ill COVID-19 patients.
Ongoing trials
Gemtuzumab ozogamicin
- Monoclonal antibody that binds to CD33-expressing tumour cells to induce cell cycle arrest and apoptotic cell death;
- Indicated for CD33-positive acute myeloid leukaemia.
Ongoing trials
Namilumab
- Human immunoglobulin G1 monoclonal antibody currently in late-stage trials for the treatment of rheumatoid arthritis and ankylosing spondylitis;
- Currently being investigated to see if it can help manage inflammation associated with COVID-19.
Ongoing trials
- CATALYST.
Infliximab
- Chimeric monoclonal antibody indicated to treat inflammatory conditions, including rheumatoid arthritis and inflammatory bowel disease;
- Currently being investigated to see if it can help manage inflammation associated with COVID-19.
Ongoing trials
- CATALYST.
Adalimumab
- An anti-tumour necrosis factor (TNF) drug already used for a wide-range of inflammatory conditions including rheumatoid arthritis and inflammatory bowel disease;
- Recent studies of patients with COVID-19 have shown that patients already taking anti-TNF drugs for other conditions were less likely to be admitted to hospital.
Ongoing trials
Otilimab
- Monoclonal antibody already in trials for the treatment of arthritis;
- May be able to help to block the effects of one of the types of cytokine (known as GM-CSF).
Evidence
- GlaxoSmithKline announced results from the phase II proof of concept OSCAR study with otilimab which showed that in patients of all ages treatment difference was not statistically significant between the otilimab and standard of care groups, but in analysis by age, patients 70 years and older had an increased chance of being alive and free of respiratory failure 28 days after treatment with otilimab compared to the standard care group (65.1% vs 45.9%);
Ongoing trials
Medi3506
- Interleukin-33 monoclonal antibody developed for skin disorders.
Ongoing trials
- ACCORD.
Antiviral antibody cocktail
- Several companies are developing novel monoclonal antibodies to bind to and neutralise the SARS-CoV-2 virus;
- This ‘antiviral antibody cocktail’ contains two antibodies and trials will investigate whether the therapy can improve the outcomes for COVID-19 patients;
- It will also be tested as a preventive therapy in those who are healthy but at high risk of getting sick because they work in a healthcare setting or have been exposed to an infected person;
- REGN-COV2 comprises two monoclonal antibodies, REGN10933 and REGN10987, and was designed specifically by Regeneron scientists to block infectivity of SARS-CoV-2.
Evidence
- In an interim analysis, the REGN-COV2 antibody cocktail was found to reduce viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group (Weinreich et al. 17 December 2020);
- Regeneron Pharmaceuticals, Inc. announces positive, prospective results from an ongoing Phase 2/3 seamless trial in the COVID-19 outpatient setting showing its investigational antibody cocktail, REGN-COV2, met the primary and key secondary endpoints. REGN-COV2 significantly reduced viral load and patient medical visits (28 October 2020).
Ongoing trials
- RECOVERY (REGN-COV2);
- ‘Safety, Tolerability and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for Hospitalised Adult Patients with COVID-19’ PAUSED 30 October 2020;
- Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Adult Patients With COVID-19;
- Phase III trial will evaluate the use of the antibody cocktail, REGN-COV2, to prevent infection among uninfected people who have had close exposure to a COVID-19 patient;
- REGN-COV2 has also moved into the Phase 2/3 portion of two adaptive Phase 1/2/3 trials testing the cocktail’s ability to treat hospitalised and non-hospitalised (or “ambulatory”) patients with COVID-19.
Leronlimab
- An investigational humanised monoclonal antibody targeted against the CCR5 receptor, which appears to play a central role in modulating immune cell trafficking to sites of inflammation;
- Being looked at as a potential therapy in the treatment of triple negative breast cancer and HIV infection as well as COVID-19.
Ongoing trials
LY-CoV555/bamlanivimab
- LY-CoV555 is a potent neutralising IgG1 monoclonal antibody directed against the spike protein on SARS-CoV-2;
- Designed to block viral attachment and entry into human cells, thus neutralising the virus, potentially preventing and treating COVID-19.
Evidence
- Initial results from the BLAZE-2 trial suggest that nursing home residents randomised to bamlanivimab have up to an 80% lower risk of contracting COVID-19 versus residents in the same facility randomised to placebo (21 January 2021);
- Treatment with bamlanivimab and etesevimab combination therapy, but not bamlanivimab monotherapy, resulted in a reduction in SARS-CoV-2 log viral load at day 11 in patients with mild to moderate COVID-19 (Gottlieb et al, 21 January 2021);
- Interim analysis of the BLAZE-1 trial found that one of three doses (2800mg) of the neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time in patients with mild or moderate COVID-19, whereas the other doses (700mg and 7000mg) administered had not by day 11 (Chen et al, 28 October 2020);
- The ACTIV-3 trial, which is evaluating multiple investigational agents in hospitalised patients with COVID-19, stopped randomising patients to treatment with LY-CoV555 based on an analysis suggesting that the antibody was not beneficial in this population (26 October 2020).
Ongoing trials
- A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness (BLAZE-1);
- A Study of LY3819253 (LY-CoV555) in Preventing SARS-CoV-2 Infection and COVID-19 in Nursing Home Residents and Staff (BLAZE-2);
- ACTIV-2: A Study for Outpatients With COVID-19;
- ACTIV-3: Therapeutics for Inpatients With COVID-19 (TICO) PAUSED 13 October 2020
LY-CoV016/etesevimab
- Also known as JS016, LY-CoV016 is a recombinant human monoclonal neutralising antibody;
- Targets the SARS-CoV-2 spike protein and blocks binding of the virus to the ACE2 host cell surface receptor;
- Effective for both prophylactic and therapeutic venues against SARS-CoV-2 infection in rhesus macaques.
Evidence
- Treatment with bamlanivimab and etesevimab combination therapy, but not bamlanivimab monotherapy, resulted in a reduction in SARS-CoV-2 log viral load at day 11 in patients with mild to moderate COVID-19 (Gottlieb et al, 21 January 2021).
Ongoing trials
- A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness (BLAZE-1).
Risankizumab
- Risankizumab is an anti-IL-23 monoclonal antibody developed by Boehringer Ingelheim and AbbVie;
- Being investigated for the treatment of multiple inflammatory diseases, including psoriasis, Crohn’s disease, ulcerative colitis, atopic dermatitis and psoriatic arthritis;
- Approved in the US in 2019 for the treatment of severe plaque psoriasis;
- Will be tested in conjunction with the antiviral drug remdesivir, compared to a placebo plus remdesivir.
Ongoing trials
Lenzilumab
- Investigational recombinant monoclonal antibody targeting human GM-CSF, which is thought to have a role in the pathogenesis of COVID-19–related immune hyper-response;
- Currently being tested in a phase III COVID-19 study and in a phase 1b/2 study as sequenced therapy with CAR-T treatments.
Ongoing trials
IMU-838
- IMU-838 is a next-generation selective immune modulator that inhibits the intracellular metabolism of activated immune cells by blocking the enzyme, dihydroorotate dehydrogenase;
- Investigational drug under development as an oral tablet formulation for the treatment of relapsing-remitting multiple sclerosis, inflammatory bowel disease and other chronic inflammatory and autoimmune diseases;
- Also being investigated as a potential treatment option for COVID-19.
Ongoing trials
- A Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 as Addition to Investigator’s Choice of Standard of Care Therapy, in Patients With Coronavirus Disease 19 (COVID-19);
- IMU-838 and Oseltamivir in the Treatment of COVID-19 (IONIC).
Other or multiple mechanisms

Source: Shutterstock.com
Colchicine
- Medicine for treating inflammation and pain in conditions such as gout;
- Could help ameliorate COVID-19 complications, but there is minimal anecdotal experience and clinical trial data reported to date in COVID-19.
Evidence
- A COVID-19 Therapeutic Alert published by the Department of Health and Social Care on 12 February 2021 states that colchicine should not be used in the management of COVID-19 positive patients other than in the context of a trial, or unless there is an additional licensed indication for its use;
- A small study suggests that colchicine reduced the length of both supplemental oxygen therapy and hospitalisation. The drug was safe and well tolerated. It was not possible to ensure that colchicine reduced mortality of COVID-19 (Lopes et al. 4 February 2021);
- Early results from the COLCORONA trial have shown that the use of colchicine was associated with reductions in the risk of death or hospitalisation compared to placebo; in patients with a proven diagnosis of COVID-19, colchicine reduced hospitalisations by 25%, the need for mechanical ventilation by 50%, and deaths by 44% (23 January 2021);
- Participants who received colchicine had statistically significant improved time to clinical deterioration compared with a control group that did not receive colchicine. However, the authors said that the findings should be considered only hypothesis-generating, given the low enrolment and event rates (Deftereos et al, 24 June 2020).
Ongoing trials
- RECOVERY (27 November 2020);
- COLCORONA;
- The Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention (GRECCO-19);
- ‘Colchicine Counteracting Inflammation in COVID-19 Pneumonia’ (COLCOVID-19);
- ‘The ECLA PHRI COLCOVID Trial: Effects of Colchicine on Moderate/High-risk Hospitalized COVID-19 Patients’ (COLCOVID).
Angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers
- Indicated for the treatment of hypertension and heart failure;
- There have been suggestions that the drugs can increase both the risk of infection and the severity of SARS-CoV2, but data are lacking;
- May also have a protective effect against lung damage.
Evidence
- Severity of COVID-19 is not associated with the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers;
- The BRACE CORONA trial, which tested temporarily stopping an ACE inhibitor/ARB for 30 days versus continuing ACE inhibitors/ARBs in patients who were taking these medications chronically and were hospitalised with a confirmed diagnosis of COVID-19, found no clinical difference, suggesting the medication should generally be continued for those with an indication (Lopes et al, presented at the European Society of Cardiology Congress 2020 on 1 September 2020).
Ongoing trials
- ‘Losartan for Patients With COVID-19 Requiring Hospitalization’;
- ‘Recombinant Human Angiotensin-Converting Enzyme 2 (rhACE2) as a Treatment for Patients with COVID-19’ (APN01-COVID-19).
Statins
- Indicated for the treatment of cardiovascular disease;
- Decrease inflammation, reduce blood clots, and prevent damage to endothelial tissue;
- Some evidence they can act as antivirals;
- Could potentially combat CRS in severely ill patients, but concrete data are lacking.
Ongoing trials
Aspirin
- Triple effect of inhibiting virus replication, anticoagulation and anti-inflammatory.
Ongoing trials
Clopidogrel
- Anti-platelet drug that could help prevent blood-clots associated with COVID-19.
Ongoing trials
- C-19-ACS.
Anticoagulants
- Potential role of anticoagulation in specific COVID-19 patients for improved mortality.
Evidence
- Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with COVID-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events (Rentsch et al. 11 February 2021).
Ongoing trials
- REMAP-CAP;
- ‘Weight-Adjusted versus Fixed Low Doses of Low-Molecular-Weight Heparin for Venous Thromboembolism Prevention in COVID-19’ (COVI-DOSE);
- ‘Antithrombotic Therapy to Ameliorate Complications of COVID-19’ (ATTACC);
- ‘Preventing COVID-19 Complications with Low- and High-Dose Anticoagulation’ (COVID-HEP);
- ‘Effect of Anticoagulation Therapy on Clinical Outcomes in COVID-19’ (COVID-PREVENT);
- C-19-ACS.
Bemcentinib
- Selectively inhibits AXL kinase, which blocks viral entry and enhances the antiviral type I IFN response;
- Investigational treatment for COVID-19;
- Reported to exhibit potent anti-viral activity in pre-clinical models against several enveloped viruses, including Ebola and Zika virus.
Ongoing trials
Omeprazole
- Proton-pump inhibitor indicated for the treatment of gastroesophageal reflux disease (GORD);
- Being investigated as an additive treatment for COVID-19.
Ongoing trials
- C-19-ACS.
Famotidine
- Histamine-2 receptor antagonist used in the treatment of GORD;
- Some evidence to suggest it is associated with improved patient-reported outcomes in non-hospitalised patients with COVID-19.
Ongoing trials
Zilucoplan
- Synthetic macrocyclic peptide inhibitor already in trial for potential treatment of the skeletomuscular disorder myasthenia gravis;
- Could reduce damage to lung tissue caused by the virus.
Ongoing trials
- ACCORD.
Ascorbic acid/vitamin C
- Use of vitamin C could be effective in terms of mortality and secondary outcomes in patients with COVID-19 pneumonia due to its anti-inflammatory and antioxidant properties.
Evidence
- Evidence from a randomised clinical trial of 214 patients suggests that treatment with zinc, ascorbic acid, or both does not affect SARS-CoV-2 symptoms (Thomas et al. 12 February 2021).
Ongoing trials
- ‘Lessening Organ Dysfunction with Vitamin C (LOVIT);
- ‘Use of Ascorbic Acid in Patients with COVID 19’;
- Coronavirus 2019 (COVID-19)- Using Ascorbic Acid and Zinc Supplementation (COVIDAtoZ)
Aviptadil
- Synthetic form of human vasoactive intestinal peptide;
- Indicated for treatment of erectile dysfunction;
- Reduces inflammation in the lungs and protects the alveolar type II cells that are believed to be an entry route for the SARS-CoV-2 to invade the lungs.
Ongoing trials
- ‘Inhaled Aviptadil for the Treatment of Non-Acute Lung Injury in COVID-19’ (AVINALI);
- ‘Intravenous Aviptadil for Critical COVID-19 With Respiratory Failure’ (COVID-AIV).
Opaganib
- Selectively inhibits sphingosine kinase-2 (SK2), a lipid-signalling molecule that promotes cancer growth;
- Currently under investigation for oncology, inflammatory and gastrointestinal indications;
- Pre-clinical studies have shown opaganib to have anti-inflammatory and anti-viral activity;
- In vivo studies have shown opaganib to decrease fatality rates from influenza.
Ongoing trials:
Tradipitant
- A neurokinin-1 receptor antagonist that works by blocking substance P, a neuropeptide secreted by neuronal cells and inflammatory cells that has multiple effects in different tissues;
- Currently in clinical development for gastroparesis, motion sickness and atopic dermatitis.
Evidence
Ongoing trials
AZD1656
- A glucokinase activator that has been shown to reduce blood glucose for up to four months in humans;
- Has also been shown to activate the migration of T regulatory cells to sites of inflammation in preclinical experiments;
- May prevent the development of cardiorespiratory complications observed in hospitalised patients with COVID-19;
- AZD1656 has already undergone phase ll trials for use in type 2 diabetes and is currently under clinical investigation for renal transplant rejection.
Ongoing trials
Nitric oxide
- Nitric oxide (NO) inhalation has been used as a pulmonary vasodilator and has been found to have antiviral activity against other coronavirus strains;
- Preliminary data support a microbicidal effect of high concentration inhaled NO;
- NO is being investigated to see if it can prevent the deterioration to a severe form of COVID-19 when administered at an early stage of the disease.
Ongoing trials
- Nitric Oxide Inhalation Therapy for COVID-19 Infections in the ED (NO COV-ED);
- Inhaled Nitric Oxide Gas Therapy in Mechanically Ventilated Patients with Severe Acute Respiratory Syndrome in COVID-19;
- Nitric Oxide Releasing Solution to Treat and Prevent Exacerbation of Mild COVID-19 Infection.
Razuprotafib
- Investigational drug that activates Tie2 receptor proteins on the surface of endothelial cells to bind to angiopoietins; a key pathway in the formation, repair and stabilisation of blood vessels;
- May prevent and treat respiratory distress in COVID-19 patients;
- Pre-clinical studies and clinical data suggest promise for the drug in aiding COVID-19 patients.
Ongoing trials:
Fluvoxamine
- Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) used primarily for the treatment of obsessive–compulsive disorder;
- It is thought that fluvoxamine may prevent clinical deterioration in patients with COVID-19 by stimulating the σ-1 receptor, which regulates cytokine production.
Evidence
- In a small preliminary study, adult outpatients with symptomatic COVID-19 treated with fluvoxamine, compared with placebo, had a lower likelihood of clinical deterioration over 15 days; however, determination of clinical efficacy would require larger randomized trials with more definitive outcome measures (Lenze et al. 12 November 2020).
Ongoing trials
This article will be updated regularly as more information emerges. If there are any trials or treatments we have missed, let us know.
Other sources of information:
- American Society of Health-System Pharmacists: https://www.ashp.org/-/media/assets/pharmacy-practice/resource-centers/Coronavirus/docs/ASHP-COVID-19-Evidence-Table.ashx?la=en&hash=B414CC64FD64E1AE8CA47AD753BA744EDF4FFB8C
- National Institute of Health Research: https://www.nihr.ac.uk
- ClinicalTrials.gov: https://clinicaltrials.gov
- EU Clinical Trials Register: https://www.clinicaltrialsregister.eu
- 1Treatments and vaccines for COVID-19 . European Medicines Agency. 2020.https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines-covid-19 (accessed 2021).