Letters to participants

Second letter to parents of child participants

RECOVERY Central Coordinating Office
Nuffield Department of Population Health
Richard Doll Building, Old Road Campus
Roosevelt Drive, Oxford, OX3 7LF

Tel: 0808 164 4060
Email: recoverytrial@ndph.ox.ac.uk
Website: www.recoverytrial.net

[ID number]

Dear parent/guardian of [child’s name],

Participation in the RECOVERY trial

On behalf of the University of Oxford and local hospital trial teams, we wish to thank you for agreeing that [child’s name] could take part in the Randomised Evaluation of COVID-19 Therapy (RECOVERY) Trial. This is the largest clinical trial in the world to find effective treatments against the effects of COVID-19 for patients in hospital.

We are writing to update you on the results of the part of the trial that aimed to find an effective treatment for children in hospital with a condition called paediatric inflammatory multisystem syndrome (PIMS) because of a COVID-19 infection. PIMS causes inflammation in the body when the immune system fights off the virus but then overreacts to affect other parts of the body.

You can read more about the the trial and the treatments tested on the second page of this letter and on the RECOVERY website at www.recoverytrial.net/news.

Results of the trial

Your child’s participation in RECOVERY has helped us to find out that:

Initial treatment with methylprednisolone is effective at reducing the length of time that children with PIMS need to spend in hospital;
If symptoms do not improve, tocilizumab is an effective treatment for reducing the length of time that children with PIMS need to spend in hospital;
Immunoglobulin was not an effective treatment for PIMS;
Some children who were given methylprednisolone and tocilizumab needed more heart support medicines than children not given these added treatments, but all the treatments were found to be safe for children.

We were not able to find out if anakinra was effective because the number of children being admitted with PIMS became very small.

The trial ‘in a nutshell’

The only way to find out whether or not a potential treatment works is to assess it in a randomised controlled trial. This means that a number of similar people are randomly selected to either receive a treatment or are put into a group that does not receive the treatment. Researchers can then compare what happens to those who receive the treatment with what happens to those who do not.

With your consent, [child’s name] was randomly assigned to receive either the care offered in your hospital alone or the hospital care with an added treatment. The RECOVERY trial initially evaluated two treatments in children aged under 18: methylprednisolone, a type of steroid that helps to reduce inflammation, and immunoglobulin, an antibody treatment that helps the immune system’s ability to fight infections.

For some children who needed further treatment, the trial also assessed two treatments for children whose symptoms did not improve initially. The second treatments were tocilizumab and anakinra, both of which are usually used to reduce inflammation in people with rheumatoid arthritis.

In total, 237 children took part in the trial and the average age of those was about 9.5 years old. The trial researchers looked at how long the children needed to stay in hospital and assessed a range of other factors, including whether or not they needed heart support medicines and measures of levels of inflammation in the body. The trial also assessed the safety of each of the tested treatments by looking at any potential side effects.

Going ‘behind the scenes’ of the trial

On Clinical Trials Day (20 May 2023), we launched a video featuring two members of the trial’s Coordinating Centre team; a trial participant, Elaine Bowden; a clinician, Dr Raha West; and the former Government Chief Scientific Adviser, Sir Patrick Vallance.
The RECOVERY trial has received several prestigious awards, all of which recognise the contribution made by participants, most recently from the Galien Foundation for ‘Best Public Sector Innovation’ and the Medical Research Council for ‘Outstanding Team Impact’.

You can see the video and read more about these highlights in the news section of the RECOVERY website at recoverytrial.net/news. The news section of the website also has an article describing how RECOVERY successfully enabled the participation of pregnant women, so that we have information about treatments that are suitable for them.

How we are using your child’s data

All information about your child and their health is kept private. Data from which your child cannot be recognised may be shared with other research groups who are doing similar research. There is more information about this in the ‘For patients in the UK’ section of the trial website (recoverytrial.net/patients).

Researchers working on other studies can now apply to access RECOVERY trial data so that they can answer new research questions using data that have already been collected. The researchers must prove that their work will help public health and they will only be provided with the information needed to answer their specific question (and no information that identifies your child). You can find out more about this in an animation in the ‘For patients’ section of the trial website.

Communicating with us

If you would like to discuss anything in this newsletter, or any other aspect of the study, with a member of the study team you can contact us by phone (0808 164 4060 Monday to Friday between 9am-5pm), email or post (details at the top of this letter). Please quote the participant ID number in any correspondence. If you would prefer to speak to the doctors at your local hospital, we can put you in touch with them.

This letter was sent to you on behalf of RECOVERY by NHS England via APS (an NHS-approved mailing house).

Thank you again for your support in this remarkable effort to save the lives of patients with COVID-19.

Yours sincerely,

Professor Sir Martin Landray and Professor Sir Peter Horby, Chief Investigators

Letter to child participants who are now adults

[ID number]

Dear [name],

Participation in the RECOVERY trial

On behalf of the University of Oxford and local hospital trial teams, we wish to thank you for taking part in the Randomised Evaluation of COVID-19 Therapy (RECOVERY) Trial, with your parents’ consent. This is the largest clinical trial in the world to find effective treatments against the effects of COVID-19 for patients in hospital.

You can read more about the the trial and the treatments tested on the second page of this letter and on the RECOVERY website at www.recoverytrial.net/news.

Results of the trial

Your participation in RECOVERY has helped us to find out that:

Initial treatment with methylprednisolone is effective at reducing the length of time that children with PIMS need to spend in hospital;
If symptoms do not improve, tocilizumab is an effective treatment for reducing the length of time that children with PIMS need to spend in hospital;
Immunoglobulin was not an effective treatment for PIMS;
Some children who were given methylprednisolone and tocilizumab needed more heart support medicines than children not given these added treatments, but all the treatments were found to be safe for children.

We were not able to find out if anakinra was effective because the number of children being admitted with PIMS became very small.

The trial ‘in a nutshell’

With your parents’ consent, you were randomly assigned to receive either the care offered in your hospital alone or the hospital care with an added treatment. The RECOVERY trial initially evaluated two treatments in children aged under 18: methylprednisolone, a type of steroid that helps to reduce inflammation, and immunoglobulin, an antibody treatment that helps the immune system’s ability to fight infections.

Other recent highlights

On Clinical Trials Day (20 May 2023), we launched a video featuring two members of the trial’s Coordinating Centre team; a trial participant, Elaine Bowden; a clinician, Dr Raha West; and the former Government Chief Scientific Adviser, Sir Patrick Vallance.
The RECOVERY trial has received several prestigious awards, all of which recognise the contribution made by participants, most recently from the Galien Foundation for ‘Best Public Sector Innovation’ and the Medical Research Council for ‘Outstanding Team Impact’.

How we are using your data

All information about you and your health is kept private. Data from which you cannot

be recognised may be shared with other research groups who are doing similar

research. There is more information about this in the ‘For patients in the UK’ section of the trial website (recoverytrial.net/patients).

Researchers working on other studies can now apply to access RECOVERY trial data so that they can answer new research questions using data that have already been collected. The researchers must prove that their work will help public health and they will only be provided with the information needed to answer their specific question (and no information that identifies you). You can find out more about this in an animation in the ‘For patients’ section of the trial website.

Communicating with us

This letter was sent to you on behalf of RECOVERY by NHS England via APS (an NHS-approved mailing house).

Thank you again for your support in this remarkable effort to save the lives of patients with COVID-19.

Yours sincerely,

Professor Sir Martin Landray and Professor Sir Peter Horby, Chief Investigators

Third letter to adult participants

[ID number]

Dear Participant,

An update on the RECOVERY trial

On behalf of the University of Oxford, we would like to thank you for taking part in the Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, and to give you an update on the study’s progress.

Although COVID-19 restrictions are no longer in place, new coronavirus variants may emerge and it is important that we have treatments that are effective against many strains of the virus. So, the RECOVERY trial is continuing to investigate potential COVID-19 treatments in patients hospitalised by the disease.

To date, the trial has involved over 47,000 participants in the UK and more than 1500 from its overseas sites in Asia and Africa. It remains the largest study of COVID-19 treatments in the world, and your contribution has played a vital part in the study’s impact. Thanks to the results from the study, patients hospitalised with COVID-19 now receive better treatment than before.

Trial results

When we wrote to you last, RECOVERY had discovered three treatments that reduce deaths from COVID-19:

Dexamethasone, an inexpensive corticosteroid treatment, reduces deaths from COVID-19 by up to a third for hospitalised patients requiring oxygen or a mechanical ventilator (June 2020).
An arthritis treatment, tocilizumab, adds to the benefit of dexamethasone in reducing deaths from COVID-19 (February 2021).
An antibody treatment developed specifically to treat COVID-19, now known as Ronapreve, reduced the risk of death when given to patients who had not produced their own antibodies to the virus (June 2021).

Since then, the RECOVERY trial has found an additional effective treatment against COVID-19: baricitinib, an anti-inflammatory drug normally used to treat rheumatoid arthritis. Treatment with baricitinib reduced deaths, shortened hospital stays, and also reduced the risk of progressing to invasive mechanical ventilation or death.

The RECOVERY trial has also found out that nine other treatments are not effective for patients hospitalised with COVID-19. We have also found that higher doses of corticosteroids increased the risk of death for some patients who were moderately unwell, but we are still investigating whether this treatment benefits the sickest people who require more intensive forms of respiratory support. These results are very important as the treatments might otherwise be used for patients hospitalised with COVID-19, without benefitting them but also taking up time and money.

This means that the RECOVERY trial has delivered results on 13 different treatments. Since most clinical trials take years to deliver a single result, this is an amazing achievement. You can read more about these results at the end of this letter and in the news section of the RECOVERY website at recoverytrial.net/news.

The RECOVERY trial is continuing to investigate two treatments: sotrovimab, an investigational monoclonal antibody that may be effective against the Omicron variant; and high dose corticosteroids in patients who need breathing support from a machine.

A global study

In February 2021, the RECOVERY trial launched internationally to help identify affordable, effective treatments that can be used in less well-resourced settings. Nepal, Indonesia and Vietnam were the first countries to join. South Africa, Ghana, and India have also joined the study. Currently, RECOVERY International includes 24 hospital sites across these six countries.

Going ‘behind the scenes’ of the trial

A wide range of different people have played an essential part in making the RECOVERY trial happen. You can learn more about these through a collection of interviews that go ‘behind the scenes’ of the study on the RECOVERY trial website (recoverytrial.net/case_studies). These profiles include a doctor; a participant; a research nurse; NHS Blood and Transplant; a pharmacist; the study’s international partners in Indonesia, and the communications and IT teams. Other recent highlights

On Clinical Trials Day (20 May) this year, we launched a video featuring two members of the trial’s Coordinating Centre team; a trial participant, Elaine Bowden; a clinician, Dr Raha West; and the former Chief Scientific Adviser, Sir Patrick Vallance.
The news section of the website also contains an article describing how RECOVERY successfully enabled the participation of pregnant women, so that we have information about treatments that are suitable for them.
The RECOVERY trial has received several prestigious awards, all of which recognise the contribution made by participants, most recently from the Galien Foundation for ‘Best Public Sector Innovation’ and the Medical Research Council for ‘Outstanding Team Impact’.

You can see the video and read more about these highlights in the news section of the RECOVERY website at recoverytrial.net/news.

Communicating with you

We would like to write to you periodically with updates on the progress of the trial. If you would like to receive these updates via email instead, please sign up via our website at recoverytrial.net/patients. You will need your study ID number shown at the top of this letter.

If you would like to discuss anything in this newsletter, or any other aspect of the study, with a member of the study team you can contact us by phone (0808 164 4060 Monday to Friday between 9am-5pm), email or post (details at the top of this letter). Please quote your participant ID number in any correspondence. If you would prefer to speak to the doctors at your local hospital, we can put you in touch with them.

This letter was sent to you on behalf of RECOVERY by NHS England via APS (an NHS-approved mailing house).

Thank you again for your participation in this remarkable effort to save the lives of patients with COVID-19.

Yours sincerely,

Professor Sir Martin Landray and Professor Sir Peter Horby, Chief Investigators

Further information about the treatments tested in the RECOVERY trial

The following treatments were found to be effective:

Dexamethasone (a steroid treatment): In June 2020, we found that this drug reduced deaths by one third in patients who received treatment with a ventilator and by one fifth in patients receiving oxygen only. That means that one death is prevented for every eight patients on ventilators who receive the treatment, and one death is prevented for every 25 patients on oxygen alone. Within hours of announcing these results, doctors started using dexamethasone to treat patients in the UK. NHS England have estimated that dexamethasone saved over a million lives worldwide between announcement of this breakthrough result in June 2020 and March 2021.
Tocilizumab (an anti-inflammatory treatment given by injection): In February 2021, we found that tocilizumab, an established treatment for arthritis, added to the benefit of dexamethasone in improving outcomes of patients with COVID-19. Tocilizumab significantly reduced deaths, reduced the chance of progressing to treatment with a ventilator, and shortened hospital stays. The combination of dexamethasone and tocilizumab reduced deaths by about one third for patients requiring simple oxygen and nearly one half for those requiring invasive mechanical ventilation. Tocilizumab is now part of the standard care for those patients on oxygen support who are likely to benefit.
Ronapreve (an antibody treatment developed by Regeneron Pharmaceuticals). The treatment uses a combination of two antibodies which prevent the virus from infecting cells. In June 2021, we found that this treatment reduces the risk of death when given to patients who have not produced antibodies to the virus themselves. The treatment is less effective against the Omicron variant and so it is recommended for use for other COVID-19 variants.
Baricitinib (an anti-inflammatory treatment for rheumatoid arthritis): In March 2022, we found that baricitinib reduces the risk of death when given to hospitalised patients with severe COVID-19. The benefit was in addition to those of dexamethasone and tocilizumab, the two other anti-inflammatory treatments which had previously been shown to reduce the risk of death in these patients (see above).

The following treatments were found not to be effective:

Hydroxychloroquine (a treatment for malaria): Hydroxychloroquine has been used to treat COVID-19 patients despite a lack of evidence. In early June 2020, we concluded that this drug did not reduce the number of deaths or the length of time patients with COVID-19 spent in hospital, or benefit patients in any other way. As a result, hydroxychloroquine was removed from the RECOVERY trial and guidelines for doctors were updated.
Lopinavir-ritonavir (an antiviral treatment commonly used to treat HIV): In June 2020, we also found that there is no beneficial (or harmful) effect of lopinavir-ritonavir in patients hospitalised with COVID-19. This treatment had been recommended in many countries, but it has now been removed from the trial and relevant guidelines have been updated.
Azithromycin (an antibiotic that also reduces inflammation): In December 2020, we found that azithromycin is not an effective treatment for patients hospitalised with COVID-19. Azithromycin had been used to treat COVID patients because of its theoretical potential to reduce lung inflammation.
Convalescent plasma: This is part of the donated blood from those who have recovered from COVID-19 which contains antibodies against the SARSCoV-2 virus that causes COVID-19. In January 2021, we stopped this part of the trial because there was no convincing evidence that convalescent plasma benefitted patients admitted to hospital with COVID-19. We are grateful, however, for the generous donation of plasma by patients recovered from COVID-19, coordinated by NHS Blood and Transplant.
Colchicine (a common anti-inflammatory treatment): In March 2021, we concluded that there was no convincing evidence that colchicine improved outcomes of patients with COVID-19. RECOVERY evaluated colchicine as it is used to treat various inflammatory conditions (such as gout) and had the potential to reduce symptoms of severe COVID-19.
Aspirin (commonly used to thin the blood): In June 2021, we found that aspirin does not reduce the numbers of people dying from severe COVID-19 or help to prevent patients progressing to treatment with a ventilator. There was a slight reduction in the time that patients needed to stay in hospital.
Dimethyl fumarate (anti-inflammatory drug usually prescribed to treat multiple sclerosis and psoriasis): We assessed dimethyl fumarate to find out whether it reduced the severity of COVID-19 after five days of treatment. It was thought that the drug might reduce the inflammation involved in the lung damage caused by COVID-19, but we have found that it does not provide any benefit in patients admitted to hospital. This was the first trial of this treatment for COVID-19, so this result helped us to understand more about lung damage in COVID-19, and to focus on other treatments that may be effective.
Empagliflozin (a treatment for diabetes, kidney disease and heart failure): It had been thought that empagliflozin might protect against organ damage and improve outcomes for patients with COVID-19, but in April 2023, we announced that empagliflozin did not reduce deaths from COVID-19 or provide any other benefits to severely ill patients.
Higher dose corticosteroids: RECOVERY has demonstrated that low doses of corticosteroids reduce the risk of death for patients admitted to hospital for COVID-19. There had been interest in whether using a higher dose of corticosteroids would provide additional benefits. In April 2023, we found that using higher doses of corticosteroids resulted in an increased risk of death for certain patients ─ adults with low blood oxygen levels or receiving simple oxygen therapy but who did not require more intensive breathing support. We are still investigating whether this treatment benefits those requiring more intensive forms of respiratory support.

We have stopped recruiting patients to test these treatments:

Molnupiravir, an antiviral tablet treatment originally developed for influenza; and
Paxlovid, another antiviral treatment.

We are currently analysing the results ready for publication.

We are continuing to enrol patients to test these treatments:

Sotrovimab, a monoclonal antibody that may be effective for the Omicron variant; and
Higher dose corticosteroids in the sickest patients who need mechanical breathing support.

You can read more about the results from the trial and the treatments being tested on our website at recoverytrial.net.

How we are using your data

All information about you and your health is kept private. Data from which you cannot be recognised may be shared with other research groups who are doing similar research. There is more information about this in the ‘For patients’ section of the trial website (recoverytrial.net/patients).

We are collaborating with other research groups to generate the best possible scientific information about COVID-19 treatments. For any participants who have also entered the ISARIC4C study (isaric4c.net), we may combine your data from the two research studies, in a secure and confidential manner, to gain insights that would not be possible through either study alone.

Researchers working on other studies can now apply to access RECOVERY trial data so that they can answer new research questions using data that have already been collected. The researchers must demonstrate that their work will benefit public health and they will only be provided with the information needed to answer their specific question. You can find out more about this in an animation in the patients’ section of the trial website.

Second letter to adult participants

[ID number]

Dear Participant,

An update on the RECOVERY trial

On behalf of the University of Oxford, we would like to thank you for taking part in the Randomised Evaluation of COVID-19 Therapy (RECOVERY) Trial, and to give you an update on the study’s progress. It is now over a year since the RECOVERY trial first started.

It is now the largest trial in the world to find effective treatments against COVID-19 for patients in hospital, with over 40,000 participants so far. Whether you participated recently, or during the very first wave of the pandemic, your contribution has played an essential role in improving the care of those who contract this devastating disease. Thanks to your involvement, patients hospitalised with COVID-19 now receive better treatment than before.

What have we learnt from RECOVERY so far?

In addition to discovering whether several drugs are effective in treating people in hospital with COVID-19 (see below for more details), we have also learnt more about how to run trials in this setting. One particular aspect we have learnt about is how we recruit patients and how they give their consent to participate.

You were recruited into RECOVERY when you were unwell with COVID-19 in hospital. If possible, the doctors and nurses at your hospital would have discussed this with you in person, but if you were too unwell then they would have sought the opinion of a ‘legal representative’ (either a relative or another doctor). On the basis of this consent you may have received study treatment in addition to the usual care given in the NHS (decided by a computer which allocated you at random - like rolling a dice - between the possible treatment options), and we collected some information about the care you received from your hospital and NHS records.

If a legal representative agreed for you to be in the trial because you were initially too unwell to discuss the trial yourself, you should have been informed about your participation before you left hospital.

We are aware that some participants whose consent was provided by a ‘legal representative’ were not given the opportunity to confirm their agreement to the study once they had recovered sufficiently to do so, for which we sincerely apologise. We have also found some evidence of other issues with the consent process for some participants (for example, consent being obtained verbally rather than in writing; the ‘legal representative’ not always being fully independent). The study has been inspected by the MHRA (the UK government’s regulatory authority) who noted these issues in some cases. They did though recognise the extraordinary circumstances in the NHS at the time, which made it hard for trial teams to discuss the trial with participants prior to hospital discharge.

We remain committed to making sure that everyone in the study knows about their participation, what is involved for them and their rights. If you have any concerns and would like to discuss your participation please see the “Communicating with you” section below. If you would prefer to speak to the doctors at your local hospital, we can put you in touch with them.

We have also put procedures in place to minimise the chances of this happening in the future in RECOVERY. These procedures have been discussed and agreed with the independent ethics committee which oversees the trial. What we have learnt will also improve future trials that would be conducted in similar circumstances.

What is involved for me from now on?

Now that you are out of hospital, we would like to do two things. First, we wish to continue to provide you with information about the study with newsletters like this one. Second, we would like to continue to obtain information about your health from your NHS records and other research databases (if you have provided information or samples to them). This is so that the study team can get more detailed and longerterm information about the effects of the study treatments on your health.

How is my information handled?

All information about you and your health will be kept private. The only people allowed to look at the information will be the doctors who are running the study, authorised staff at Oxford University and your hospital, and the regulatory authorities who check that the study is being conducted correctly. Data from which you cannot be recognised may be shared with other research groups who are doing similar research. This ‘anonymised’ information will not make it possible for you to be picked out as its source, and will not be combined with other information in a way that could allow that to be done.

A privacy notice is on the study website (https://www.recoverytrial.net/study-faq/dataprivacy). The privacy notice explains how your data are used, who can see it, and your rights, which include opting out of these newsletters and/ or opting out of providing your health information to RECOVERY.

Do I have to continue my involvement?

No. You can opt out of receiving the newsletters and/or allowing the study team access to future health information. To do so, you can contact us by phone (0808 164 4060 Monday to Friday between 9am-5pm), email or post (details at the top of this letter). Please quote your participant ID number (available at the top of this letter) in any correspondence. If we don’t hear from you, we will continue to send you newsletters and collect information about your health from your NHS records.

Trial results

The RECOVERY trial achieved its first major success in June 2020 when we discovered that the steroid dexamethasone is effective for hospitalised patients requiring oxygen or a mechanical ventilator. NHS guidelines were rapidly updated so that dexamethasone became part of standard care for future patients. Since then, we have found two other treatments that are effective for severe COVID-19:

An arthritis treatment, tocilizumab, adds to the benefit of dexamethasone in significantly reducing deaths from COVID-19.
An antibody treatment developed specifically to treat COVID-19, now known as Ronapreve, reduces the risk of death when given to patients who have not produced their own antibodies to the virus. (Antibodies are an important part of the immune system.)

We have also found out that a number of other treatments are not effective for patients hospitalised with COVID-19. Although disappointing, these results are still very important as they might otherwise be used, taking up NHS time and money for no benefit. You can read more about these results at the end of this letter and in the news section of the RECOVERY website at www.recoverytrial.net/news.

Global impact

RECOVERY has had global impact. Given its scale, the results from the RECOVERY trial are widely regarded as providing robust and reliable evidence on COVID-19 treatments and have influenced healthcare practices across many countries. For instance, NHS England have estimated that dexamethasone saved over one million lives worldwide between July 2020 and March 2021, including 22,000 in the UK.

In February 2021, the RECOVERY trial launched internationally, with trial sites in Nepal, Indonesia, and Vietnam, and with others planned around the world. This will allow us to increase the global relevance of the trial’s results, and identify affordable, effective treatments that can be used even in less well-resourced settings.

RECOVERY’s first anniversary

On 23 March 2021, we marked the first anniversary of the RECOVERY trial. As part of this, BBC Radio Four dedicated an episode of the health programme, Inside Health, to RECOVERY and the trial’s impact. You can hear the programme at https://www.bbc.co.uk/programmes/m000tccg.

This was a good opportunity to reflect on the ups and downs so far, and the remarkable support from scientists and clinical researchers, hospital ward teams, policy makers and of course, participants. We feel privileged to be part of RECOVERY, overwhelmed by the contribution of all involved, and proud of what this amazing trial has achieved – and hope you are too.

In the words of RECOVERY participant Kimberley Featherstone: ‘Being given the opportunity to participate in the RECOVERY trial was very humbling, knowing that the information they were collecting had a direct impact on the treatment of patients, and signing on was something I did gladly.'

Communicating with you

If you would like to discuss anything in this newsletter with a member of the study team you can contact us by phone (0808 164 4060 Monday to Friday between 9am5pm), email or post (details at the top of this letter). Please quote your participant ID number in any correspondence. If you would prefer to speak to the doctors at your local hospital, we can put you in touch with them.

This letter was sent to you on behalf of RECOVERY by [mailing details].

Joining our advisory group

We would also like to invite you to be part of a group to advise us on future communications and other aspects of the trial. If you would be interested in hearing more about this, please contact us. We really value the involvement of former patients in our research.

Thank you again for your participation in this remarkable effort to save the lives of patients with COVID-19.

Yours sincerely,

Professor Sir Peter Horby and Professor Sir Martin Landray, Chief Investigators

Further information about the treatments tested in the RECOVERY trial

To date, twelve treatments have either been tested, or are currently being tested, in the RECOVERY trial.

The following treatments were found to be effective:

Dexamethasone (a steroid treatment): We found that this drug reduced deaths by one third in patients who received treatment with a ventilator and by one fifth in patients receiving oxygen only. That means that one death is prevented for every eight patients on ventilators who receive the treatment, and one death is prevented for every 25 patients on oxygen alone. Within hours of announcing these results, doctors started using dexamethasone to treat patients in the UK. NHS England have estimated that dexamethasone saved over a million lives worldwide between announcement of this breakthrough result in June 2020 and March 2021.
Ronapreve (an antibody treatment developed by Regeneron Pharmaceuticals). The treatment uses a combination of two antibodies which prevent the virus from infecting cells. In June 2021, we found that this treatment reduces the risk of death when given to patients who have not produced antibodies to the virus themselves. Regeneron are collaborating with Roche to increase the global supply of the treatment and make it available to more people.
Tocilizumab (an anti-inflammatory treatment given by injection): In February 2021, we found that tocilizumab, an established treatment for arthritis, added to the benefit of dexamethasone in improving outcomes of patients with COVID-19. Tocilizumab significantly reduced deaths, reduced the chance of progressing to treatment with a ventilator, and shortened hospital stays. The combination of dexamethasone and tocilizumab reduced mortality by about one third for patients requiring simple oxygen and nearly one half for those requiring invasive mechanical ventilation. Tocilizumab is now part of the standard care for COVID-19 patients on oxygen support who are likely to benefit.

The following treatments were found not to be effective:

Aspirin (commonly used to thin the blood): In June 2021, we found that aspirin does not reduce the numbers of people dying from severe COVID-19 or help to prevent patients progressing to treatment with a ventilator. There was a slight reduction in the time that patients needed to stay in hospital.
Azithromycin (an antibiotic that also reduces inflammation): In December 2020, we found that azithromycin is not an effective treatment for patients hospitalised with COVID-19. Azithromycin had been used to treat COVID patients because of its theoretical potential to reduce lung inflammation.
Colchicine (a common anti-inflammatory treatment): In March 2021, we concluded that there was no convincing evidence that colchicine improved outcomes of patients with COVID-19. RECOVERY evaluated colchicine as it is used to treat various inflammatory conditions (such as gout) and had the potential to reduce symptoms of severe COVID-19.
Convalescent plasma: This is part of the donated blood from those who have recovered from COVID-19 which contains antibodies against the SARSCoV-2 virus that causes COVID-19. We found no convincing evidence of the effect of convalescent plasma on clinical outcomes in patients admitted to hospital with COVID-19. We are grateful, however, for the generous donation of plasma by patients recovered from COVID-19, coordinated by NHS Blood and Transplant.
Hydroxychloroquine (a treatment for malaria): Hydroxychloroquine had been used to treat COVID-19 patients despite a lack of evidence. In early June 2020, we concluded that this drug did not reduce the number of deaths or the length of time patients with COVID-19 spent in hospital, or benefit patients in any other way. As a result, hydroxychloroquine was removed from the RECOVERY trial and guidelines for doctors were updated.
Lopinavir-ritonavir (an antiviral treatment commonly used to treat HIV): We have also found that there is no beneficial (or harmful) effect of lopinavirritonavir in patients hospitalised with COVID-19. This treatment had been recommended in many countries, but it has now been removed from the trial and relevant guidelines have been updated.

We are continuing to enrol patients to test these treatments:

Baricitinib – an anti-inflammatory treatment for rheumatoid arthritis that may also work against the virus.
Dimethyl fumarate – a treatment for multiple sclerosis that alters the immune response and has demonstrated anti-viral and anti-inflammatory effects against SARS-CoV-2 in laboratory studies.
Empagliflozin – a treatment for diabetes, kidney disease and heart failure that may also protect against organ damage and improve outcomes for patients with COVID-19.

We expect that other treatments will be tested in the RECOVERY trial in the future. You can read more about the results from the trial and the treatments being tested on our website at www.recoverytrial.net.

Letter to adult participants

[ID number]

Dear [name],

Your participation in the RECOVERY trial

On behalf of the University of Oxford, we wish to sincerely thank you for taking part in the Randomised Evaluation of COVID-19 Therapy (RECOVERY) Trial. This is the largest trial in the world to find effective treatments against COVID-19 for patients in hospital.

The only way to find out whether a potential treatment works is to test it in a randomised controlled trial. This is a study in which a number of similar people are randomly selected to receive a treatment or put into a group that does not receive the treatment. Researchers can then compare what happens to those who receive the treatment with what happens to those who don’t.

During your treatment, and with your consent (or consent received from a representative if you were too unwell to give it yourself), you were randomly selected to receive either standard hospital care alone or standard hospital care with an additional treatment.

COVID-19 has been described as the greatest health challenge in this generation. When the RECOVERY trial was launched in March 2020, we did not know if there were any effective treatments for hospitalised patients.

As a national priority, the trial was launched at exceptional speed. Almost 1,000 patients were recruited in the first 15 days alone, and over 21,000 patients have now been enrolled from 176 NHS hospitals across the UK. By participating in the RECOVERY trial, you have been part of an extraordinary achievement, both in the scale and speed of its delivery, and the impact of the results.

Results so far

Your participation in RECOVERY has helped us to deliver four significant results so far. We have found out that:

A treatment for malaria, hydroxychloroquine, does not prevent death or shorten the length of time a patient needs to stay in hospital.
A widely-available steroid, dexamethasone, reduced deaths by one third in patients who received treatment with a ventilator and by one fifth in patients receiving oxygen only.
An antiviral treatment that is commonly used to treat HIV, lopinavir-ritonavir, has no beneficial effects in patients hospitalised with COVID-19.
Azithromycin, a widely used antibiotic that also reduces inflammation, is not an effective treatment for patients hospitalised with COVID-19.

You can read more about these results at the end of this letter and in the news section of the RECOVERY website at www.recoverytrial.net/news.

A crucial focus of this trial has been to share the results as soon as possible, so that any effective treatments can immediately be made available to patients. Within hours of the dexamethasone result being announced, doctors in the UK had started using it to treat patients; it is now used worldwide, potentially saving thousands of lives. Finding that treatments do not work is also important, as this means that resources can be focused on other treatments that look promising.

Communicating with you

We would like to write to you periodically with updates on the progress of the trial. If you would like to receive these updates via email instead, please sign up via our website at www.recoverytrial.net/patients. You will also find information on how we handle your data here. You will need your study ID number shown at the top of this letter. You can opt out of these communications (or ask any questions about the trial or its results) at any time by contacting us by email, phone or post, using the contact details at the top of this letter. This letter was sent to you on behalf of RECOVERY by NHS Digital via APS (an NHS-approved mailing house).

Joining our advisory group

Thank you again for your participation in this remarkable effort to save the lives of patients with COVID-19.

Yours sincerely,

Professor Peter Horby and Professor Martin Landray, Chief Investigators

Further information about the treatments tested in the RECOVERY trial

To date, nine treatments have either been tested, or are currently being tested, in the RECOVERY trial. We have tested these treatments:

Hydroxychloroquine (a treatment for malaria): Hydroxychloroquine has been widely used to treat COVID-19 patients despite a lack of evidence. In early June, the information on hydroxychloroquine that we gathered from the RECOVERY trial was reviewed and we concluded that this drug did not reduce the number of deaths or the length of time patients with COVID-19 spent in hospital, or benefit patients in any other way. As a result, hydroxychloroquine was removed from the RECOVERY trial and guidelines for doctors have been updated.

Dexamethasone (a steroid treatment): The evidence from the trial on the use of dexamethasone was also reviewed in early June. We concluded that this drug reduced deaths by one third in patients who received treatment with a ventilator and by one fifth in patients receiving oxygen only. That means that for every eight patients on ventilators who receive the treatment, one death is prevented, and for every 25 patients on oxygen alone, one death is prevented. There was no benefit among those patients who did not require oxygen.

Within hours of these results being announced, doctors started using dexamethasone to treat patients in the UK. Dexamethasone is estimated to have saved more than half a million lives worldwide since announcement of this breakthrough result. We are continuing to test steroids as a possible treatment for children with COVID-19.

Lopinavir-ritonavir (an antiviral treatment commonly used to treat HIV): We have also found that there is no beneficial (or harmful) effect of lopinavir-ritonavir in patients hospitalised with COVID-19. This treatment had previously been recommended in many countries, but it has now been removed from the trial and relevant guidelines are being updated.

Azithromycin (an antibiotic that also reduces inflammation): We have recently found that azithromycin is not an effective treatment for patients hospitalised with COVID-19. Azithromycin had been widely used to treat COVID patients because of its theoretical potential to reduce lung inflammation.

RECOVERY is continuing to enrol patients to test different treatments. These are:

Aspirin - commonly used to thin the blood
Colchicine - a commonly used anti-inflammatory treatment
Convalescent plasma - part of the donated blood from those who have recovered from COVID-19 which contains antibodies against the SARS-CoV-2 virus that causes COVID-19
Regeneron’s antibody cocktail - a new antibody treatment which is the first therapy that has been specifically designed as a potential treatment for COVID-19
Tocilizumab - an anti-inflammatory treatment.

The information in this letter may have changed since it was written. For the latest information on the RECOVERY trial, please visit the trial website, www.recoverytrial.net. The study is funded by UK Research and Innovation and the National Institute for Health Research. It is registered at ISRCTN50189673.

Letter to parents of child participants

[ID number]

Dear parent/guardian of [child’s name],

Participation in the RECOVERY trial

On behalf of the University of Oxford, we wish to sincerely thank you for agreeing that [child’s name] could participate in the Randomised Evaluation of COVID-19 Therapy (RECOVERY) Trial. This is the largest trial in the world to find effective treatments against COVID-19 for patients in hospital.

With your consent [child’s name] was randomly assigned to receive either standard hospital care alone or standard hospital care with an additional treatment.

As a national priority, the trial was launched at exceptional speed. Almost 1,000 patients were recruited in the first 15 days alone, and over 21,000 patients have now been enrolled from 176 NHS hospitals across the UK. By participating in the RECOVERY trial, they have been part of an extraordinary achievement, both in the scale and speed of its delivery, and the impact of the results.

Results so far

Your child’s participation in RECOVERY has helped us to deliver four significant results so far. We have found out that:

A treatment for malaria, hydroxychloroquine, does not prevent death or shorten the length of time a patient needs to stay in hospital.
A widely-available steroid, dexamethasone, reduced deaths by one third in patients who received treatment with a ventilator and by one fifth in patients receiving oxygen only.
An antiviral treatment that is commonly used to treat HIV, lopinavir-ritonavir, has no beneficial effects in patients hospitalised with COVID-19.
Azithromycin, a widely used antibiotic that also reduces inflammation, is not an effective treatment for patients hospitalised with COVID-19.

You can read more about these results at the end of this letter and in the news section of the RECOVERY website at www.recoverytrial.net/news.

Communicating with you

We will write to you periodically with updates on the progress of the trial. If you would like to receive updates via email instead, please sign up via our website at www.recoverytrial.net/patients. You will also find information on how we handle your data here. You will need the study ID number shown at the top of this letter. You can opt out of these communications (or ask any questions about the trial or its results) at any time by contacting us by email, phone or post, using the contact details at the top of this letter. This letter was sent to you on behalf of RECOVERY by NHS Digital via APS (an NHS-approved mailing house).

Joining our advisory group

Thank you again for your support for this remarkable effort to save the lives of patients with COVID-19.

Yours sincerely,

Professor Peter Horby and Professor Martin Landray, Chief Investigators

Further information about the treatments tested in the RECOVERY trial

To date, nine treatments have either been tested, or are currently being tested, in the RECOVERY trial. We have tested these treatments:

Lopinavir-ritonavir (an antiviral treatment commonly used to treat HIV): We have also found that there is no beneficial (or harmful) effect of lopinavir-ritonavir in patients hospitalised with COVID-19. This treatment had previously been recommended in many countries, but it has now been removed from the trial and relevant guidelines are being updated.

RECOVERY is continuing to enrol patients to test different treatments. These are:

Aspirin - commonly used to thin the blood
Colchicine - a commonly used anti-inflammatory treatment
Convalescent plasma - part of the donated blood from those who have recovered from COVID-19 which contains antibodies against the SARS-CoV-2 virus that causes COVID-19
Regeneron’s antibody cocktail - a new antibody treatment which is the first therapy that has been specifically designed as a potential treatment for COVID-19
Tocilizumab - an anti-inflammatory treatment.

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Letters to participants

Second letter to parents of child participants

Letter to child participants who are now adults

Third letter to adult participants

Second letter to adult participants

Letter to adult participants

Letter to parents of child participants