Outcomes of the UK COVID-19 Therapeutics Advisory Panel (UK-CTAP)

Contents

Recommended treatments for clinical trials

These treatments may not be approved for treating COVID-19. For the latest COVID-19 advice, talk to your GP or visit the NHS website.

About this data

This is the record of treatments recommended by the UK COVID-19 Therapeutics Advisory Panel (UK-CTAP) for clinical trials.

Each recommendation record includes:

  • treatment name
  • the trial recommended for
  • why it was recommended
  • date of recommendation.

This record does not list outcomes for treatments not yet recommended for a clinical trial.

The treatments listed could be:

  • recommended for more than one trial
  • widely used for treating other conditions
  • not yet licensed for treatments but show potential for treating COVID-19
  • formulated in a new way to target the virus.

A treatment may be recommended by the panel but not be entered into a trial.

For more information, see introduction to UK-CTAP.

Treatments recommended for trials

Aspirin

Trial recommended to: RECOVERY+

Date: 1 November 2020

Why it was recommended

Aspirin decreases the body’s ability to form blood clots. COVID-19 is known to cause clotting problems and serious illness due to extra clots forming in blood vessels, which can lead to organs being starved of blood and oxygen. Aspirin may prevent some deaths or illness by blocking the formation of clots due to COVID-19.

Specifically, aspirin is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits prostaglandin formation and suppresses the normal functioning of platelets.

 

Colchicine

Recommended to RECOVERY+

Date: 17 November 2020

Why it was recommended

Colchicine has been used for a long time to treat diseases such as arthritis, which have high levels of inflammation. COVID-19 patients have overactive inflammation in their blood and lungs from their response to infection, so colchicine might reduce this in COVID-19.

Specifically, colchicine acts on multiple mechanisms of inflammation including the inflammasome, which is thought to be activated in COVID-19.

 

Favipiravir

Trial recommended to: PRINCIPLE

Date: 17 December 2020

Why it was recommended

COVID-19 is caused by SARS-CoV-2, a virus that multiplies inside lung and other cells. Favipiravir is an antiviral drug used for influenza and similar viruses.

It works by blocking a key component in the viral machinery necessary for these viruses to multiply, and has been found in laboratory experiments to effectively stop replication of the virus causing COVID-19. It is hoped that favipiravir can reduce virus growth in early infection, therefore making the disease less severe or reducing the number of people who could become infected.

Specifically, favipiravir is a nucleoside analogue that interacts with viral RNA-dependent RNA polymerase in RNA viruses.

 

Baricitinib

Trial recommended to: RECOVERY+

Date: 11 January 2021

Why it was recommended

In people with severe COVID-19, parts of the immune system are very active, particularly in their lungs and blood, which causes inflammation and organ damage. Baricitinib blocks one of the pathways for inflammation in the body. By reducing the body’s inflammatory response, baricitinib might prevent or reduce the severity of the COVID-19 illness.

Specifically, baricitinib acts on the JAK/STAT pathway, which is a central controller of inflammation thought to be upregulated in COVID-19.

 

Dimethyl Fumarate

Trial recommended to: RECOVERY+

Date: 11 January 2021

Why it was recommended

In people with severe COVID-19, parts of the immune system are very active, particularly in their lungs and blood, which causes inflammation and organ damage.

Dimethyl fumarate blocks multiple pathways for inflammation in the body. By reducing the body’s inflammatory response, dimethyl fumarate might prevent or reduce the severity of the COVID-19 illness. It is often used in diseases where similar inflammation is an issue.

Specifically, dimethyl fumarate acts on multiple mechanisms of inflammation including the inflammasome, which is thought to be activated in COVID-19.

 

Anakinra

Trial recommended to: RECOVERY+

Date: 1 November 2020

Why it was recommended

Anakinra has been recommended for the RECOVERY+ trial in children that are affected by a rare inflammatory condition called Paediatric Multisystem Inflammatory Syndrome (PIMS-TS or PIMS), which may be linked to COVID-19. Anakinra is a medicine that is currently licensed for use in adults and children in diseases that are associated with high levels of inflammation, such as arthritis.

Specifically, anakinra binds to the interleukin 1 (IL-1) receptor and thereby reduces inflammatory IL-1 signalling, which might prevent or reduce the severity of PIMS-TS.

 

Niclosamide

Trial recommended to:

  • RECOVERY Phase 2, 23 September 2020.
  • AGILE, 1 February 2021.

Why it was recommended

Niclosamide is a drug used to treat tapeworm infections that was also found in laboratory experiments to stop the growth of SARS-CoV-2, the virus that causes COVID-19. It comes in multiple forms, for example:

  • inhaled
  • nasal drops
  • oral
  • injection.

Treatment for COVID-19 is based on niclosamide inhibiting both viral growth and inflammation.

Specifically, niclosamide has been found to inhibit TMEM16, a calcium-activated ion channel involved in viral-induced syncytia.

 

Colchicine

Trial recommended to: PRINCIPLE

Date: 1 February 2021

Why it was recommended

Colchicine has been used for a long time to treat diseases such as arthritis, which have high levels of inflammation. COVID-19 patients have overactive inflammation in their blood and lungs from response to infection, so colchicine might reduce this in COVID-19.

Specifically, colchicine acts on multiple mechanisms of inflammation including the inflammasome, which is thought to be activated in COVID-19.

 

Adalimumab

Trial recommended to: PRINCIPLE

Date: 1 February 2021

Why it was recommended

Adalimumab is widely used to treat inflammatory diseases such as arthritis. Adalimumab blocks one of the pathways for inflammation in the body. By reducing the body’s inflammatory response, adalimumab might prevent or reduce the severity of the COVID-19 illness.

Specifically, adalimumab inhibits tumour necrosis factor (TNF), a central controller of inflammation thought to be upregulated in COVID-19.

 

Atorvastatin

Trial recommended to: HEAL-COVID

Date: 10 February 2021

Why it was recommended

Statins are prescribed by doctors to reduce cholesterol, but are thought to have a number of other effects in the body including reducing inflammation and blood clotting. Emerging evidence suggests that these processes are important causes of long-term illness following COVID-19 infection. Therefore, statins might be able to counter some of these effects.

Specifically, statins have pleiotropic effects on multiple pathways relevant to COVID-19 (including anti-inflammatory, anti-thrombotic, antioxidant and immunomodulatory). These drugs have a well-understood safety profile and the benefits are likely seen across the class, but atorvastatin was selected as the optimum choice due to lower likelihood of drug interactions.

 

Apixiban

Trial recommended to: HEAL-COVID

Date: 10 February 2021

Why it was recommended

Apixiban works on the body’s ability to form blood clots and disrupts their formation. COVID-19 is known to cause clotting problems and serious illness due to extra clots forming in blood vessels, which can lead to organs being starved of blood and oxygen. Apixiban may prevent some deaths or illness by blocking the formation of clots due to COVID-19.

Specifically, apixaban is a potent, oral, reversible, direct and highly selective active site inhibitor of factor Xa. By inhibiting factor Xa, apixaban prevents thrombin generation and thrombus development

 

Namilumab

Trial recommended to: RECOVERY+

Date: 10 February 2021

Why it was recommended

In patients with severe COVID-19, overactive immune cells cause much of the damage in their lungs. By blocking these cells from multiplying and entering the lung, namilumab may prevent people from developing severe COVID-19.

Specifically, namilumab inhibits GM-CSF, a monocyte and macrophage stimulating factor that causes expansion and differentiation of inflammatory macrophage populations that are over-represented in the lungs of patients with severe COVID-19.

 

Namilumab

Trial recommended to: REMAP-CAP

Date: 12 February 2021

Why it was recommended

In patients with severe COVID-19, overactive immune cells cause much of the damage in their lungs. By blocking these cells from multiplying and entering the lung, namilumab may prevent people from developing severe COVID-19.

Specifically, namilumab inhibits GM-CSF, a monocyte and macrophage stimulating factor that causes expansion and differentiation of inflammatory macrophage populations that are over-represented in the lungs of patients with severe COVID-19.

 

Infliximab

Trial recommended to: RECOVERY+

Date: 10 February 2021

Why it was recommended

Infliximab is widely used to treat inflammatory diseases such as arthritis. Infliximab blocks one of the pathways for inflammation in the body. By reducing the body’s inflammatory response, infliximab might prevent or reduce the severity of the COVID-19 illness.

Specifically, infliximab inhibits tumour necrosis factor (TNF), a central controller of inflammation thought to be upregulated in COVID-19.

 

Infliximab

Trial recommended to: REMAP-CAP

Date: 12 February 2021

Why it was recommended

Infliximab is widely used to treat inflammatory diseases such as arthritis. Infliximab blocks one of the pathways for inflammation in the body. By reducing the body’s inflammatory response, infliximab might prevent or reduce the severity of the COVID-19 illness.

Specifically, infliximab inhibits tumour necrosis factor (TNF), a central controller of inflammation thought to be upregulated in COVID-19.

 

Prednisolone

Trial recommended to: REMAP-CAP

Date: 30 March 2021

Why it was recommended

In patients discharged from hospital after recovering from COVID-19, there is evidence of ongoing inflammation and damage to multiple organs, including the lung.

Prednisolone is a type of steroid drug that broadly suppresses inflammation in the body. In doing so, prednisolone might prevent or reduce the severity of inflammation contributing to symptoms and signs of ‘long COVID’. Steroid drugs are widely used and well understood in the clinical context of inflammation.

Specifically, prednisolone is a synthetic glucocorticoid used extensively for its broad-spectrum anti-inflammatory and immunosuppressive effects.

 

Complement (C5) inhibitors

Trial recommended to: RECOVERY+

Date: 1 February 2021

Why it was recommended

The complement pathway is an inbuilt system to remove infections, which is activated as part of the body’s response to COVID-19. However, this can also lead to high levels of inflammation in the lungs and blood, causing damage to organs as well as generation of blood clots. Complement inhibitors act on the part of the complement system that is critical to the inflammatory response, but leaves intact the parts important for killing viruses.

Specifically, drugs inhibiting C5 (the terminal complement pathway) have been recommended for trial.

 

Higher-dose dexamethasone

Trial recommended to: RECOVERY+ and REMAP-CAP

Date: 14 April 2021

Why it was recommended

Dexamethasone is a type of steroid drug that has been shown to reduce the inflammation seen in severe COVID-19.

Dexamethasone has been successful in clinical trials of COVID-19, at a medium dose of 6 mg daily. There is evidence that using these drugs at higher doses may give additional benefits in certain patients. The selected dose represents a balance between the anti-inflammatory benefits and the risks of higher doses, which are well understood from clinical practice.

Specifically, dexamethasone is a synthetic glucocorticoid used extensively for its broad-spectrum anti-inflammatory and immunosuppressive effects.

 

Pegylated interferon beta

Trial recommended to: currently no national platform

Date: 28 May 2021

Why it was recommended

As suggested by the name, interferons are naturally produced biochemicals that ‘interfere’ with viral growth. Multiple scientific studies have shown that problems with normal interferon function are associated with more severe COVID-19.

Although interferons are needed early in infection, they can possibly be harmful later on during the infection. Therefore, interferon has been recommended for trial in early COVID-19, using a product that is long-lasting and only needs to be injected under the skin once.

Interferon treatment is already used in other diseases such as multiple sclerosis, so the possible side effects and safety profile of these drugs is well understood.

Specifically, pegylated interferon beta is a long-acting type I interferon.

 

Sodium-glucose co-transporter-2 (SGLT2) inhibitors

Trial recommended to: RECOVERY Phase 3

Date: 28 May 2021

Why it was recommended

SGLT2 inhibitors are widely used to treat adults with insufficiently controlled type 2 diabetes mellitus. Additionally, SGLT2 inhibitors have been shown to have clinical benefits in heart failure and kidney disease. On this basis, SGLT2 inhibitors might reduce the severity of COVID-19 illness in a subgroup of patients that are at risk of developing serious complications.

Specifically, SGLT2 mediates glucose reabsorption. The inhibition of SGLT2 has a number of pleiotropic effects, including:

  • anti-inflammatory properties
  • anti-hypertensive properties
  • weight reduction
  • reduction in oxidative stress
  • reduction in endothelial dysfunction and atherosclerosis
  • improvement in metabolic function.

 

CSF1R inhibitors

Trial recommended to: RECOVERY+ Phase 2

Date: 28 May 2021

Why it was recommended

In patients with severe COVID-19, overactive immune cells cause much of the damage in their lungs. By blocking these cells from multiplying and entering the lung, CSF1R inhibitors may prevent people from developing severe COVID-19.

Specifically, CSF1R inhibitors block the action of CSF1, a macrophage stimulating factor that causes differentiation of monocytes into inflammatory macrophage populations that are over-represented in the lungs of patients with severe COVID-19.

 

Opaganib

Trial recommended to: RECOVERY+ Phase 2

Date: 4th August 2021

Why it was recommended

Opaganib is an oral drug which prevents the migration of white blood cells to the lungs and their activation during inflammation. By doing so, it may limit further inflammation and tissue damage in the lungs of patients with severe COVID-19.

Specifically, opaganib sequesters lymphocytes in the lymph nodes, preventing their migration to the site of inflammation. Compared to molecules of the same family, it selectively inhibits sphingosine kinase 2 (SK2), which has a specific anti-inflammatory action on lymphocytes. Its specificity for SK2 also limits the risk of side effects.

 

Metformin

Trial recommended to: HEAL-COVID

Date: 28 May 2021

Why it was recommended

Metformin is widely used to treat type two diabetes mellitus. Preliminary clinical evidence suggests that diabetic patients treated with metformin may have lower death rates than other COVID-19 patients during the pandemic. Additionally, metformin has been suggested in the scientific literature to have a range of additional characteristics that could potentially be of benefit to COVID-19 patients after hospital discharge, including effects on:

  • the heart
  • inflammation
  • fibrosis.

Specifically, metformin has glucose lowering effects. Additionally, metformin has been studied in laboratory studies and clinical trials with regards to these potential properties:

  • antifibrotic
  • cardioprotective
  • anti-inflammatory.

In particular, decreased production of inflammatory cytokines which are responsible for lung damage in COVID-19 patients. Metformin is thought to exert anti-inflammatory actions by interfering with mTOR signalling and NF-KB signalling.

 

Favipiravir IV

Trial recommended to: AGILE

Date: 6 August 2021

Why it was recommended

COVID-19 is caused by SARS-CoV-2, a virus that multiplies inside lung and other cells. Favipiravir is an antiviral drug used for influenza and similar viruses. It works by blocking an important component in the viral machinery necessary for these viruses to multiply, and has been found in laboratory experiments to effectively stop replication of the virus causing COVID-19.

It is hoped that favipiravir can reduce virus growth in early infection, therefore making the disease less severe.

Specifically, favipiravir is a nucleoside analogue that interacts with viral RNA-dependent RNA polymerase in RNA viruses.

 

Allogeneic SARS-CoV-2 virus specific T-lymphocytes

Trial recommended to: AGILE

Date: 6 August 2021

Why it was recommended

A type of white blood cell is used that specifically recognises SARS-CoV2. This treatment will compensate the deficient cellular immune response in immunodeficient patients, such as:

  • organ transplant patients
  • cancer patients receiving chemotherapy.

These individuals are particularly vulnerable to infections and cannot respond properly to immunisation.

Specifically, this product is a polyclonal mixture of allogeneic CD4 and CD8 memory T cells specific for SARS-Cov-2 spike, nucleocapsid, membrane and envelope peptides. Partial HLA-matching to recipient patients will be performed prior to administration.

 

Convalescent plasma

Trial recommended to: REMAP-CAP

Date: 6 August 2021

Why it was recommended

Even before vaccines were developed, the liquid portion of the blood that contains antibodies against the infection (termed plasma) from people that had recovered from an infectious disease was used to treat others. Indeed, during the Spanish flu pandemic in 1918, plasma from recovered patients was used. Transfer of convalescent plasma may protect or treat COVID-19 infection.

Specifically, convalescent plasma with high titres of SARS-CoV-2 IgG will be tested.

 

GTP-404

Trial recommended to: Early Phase

Date: 14 October 2021

Why it was recommended

This is early stage of development of a gene therapy approach in which treatment results in human ACE2 production as a decoy for SARS-CoV-2 to bind, since ACE2 is the protein required on cells for the COVID-19 virus to infect. Hence, the virus will bind to the decoy ACE2 rather than infecting cells.

Specifically, GTP-404 contains the non-replicating recombinant adeno-associated virus AAVrh91 carrying the human angiotensin-converting enzyme 2 (ACE2) gene defective in peptidase activity to serve as a decoy for binding SARS-CoV-2.

 

TD-0903

Trial recommended to: REMAP-CAP

Date: 10 October 2021

Why it was recommended

In people with severe COVID-19, parts of the immune system are very active, which causes inflammation and organ damage, particularly in the lungs. TD-0903 has a unique inhaled formulation which allows it to block inflammation and tissue damage directly in the lung. This might reduce severe COVID illness and the risk for patients to require to be put in ICU under ventilation.

Specifically, TD-0903 acts on the JAK/STAT pathway, which is a central controller of inflammation thought to be upregulated in COVID-19, but its inhaled formulation allows more specific inhibition of inflammation in the lung and reduces the potential side effects caused by systemic administration.

 

Sotrovimab

Trial recommended to: PROTECT-V

Date: 14 October 2021

Why it was recommended

Monoclonal antibody directed to target the spike protein that projects from SARS-CoV-2 virus particles has been developed by several pharmaceutical companies. This can be injected to supplement the generation of antibodies in individuals with weak or poor immune systems.

Specifically, sotrovimab is intended to supplement immune protection in individuals that:

  • are immunosuppressed
  • have weakened immune systems.

It uses a monoclonal antibody that targets the receptor binding domain (RBD) of the spike protein.

Last updated: 27 October 2021

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