Clinical platform trials for coronavirus (COVID-19) treatments

Contents

1. About clinical trials
2. Identifying candidates for clinical trials
3. Putting forward treatments for entry in UK trials
4. Current clinical platform trials for COVID-19 treatments in the UK
5. Results of trials to date: effective and ineffective treatments

About clinical trials

Clinical trials are essential to finding new and improved methods of treating different diseases including coronavirus (COVID-19).

Clinical trials allow us to understand whether new treatments:

• genuinely improve recovery and survival for patients who contract COVID-19
• should be made available more widely in the NHS

Phase 1 and 2 trials

Phase 1 and 2 trials are early-stage trials involving small numbers of participants to ensure a treatment is safe to use and shows evidence of a benefit beyond the standard of care.

Treatments that are found to be safe at this stage may then proceed to be tested in a phase 3 clinical trial.

Phase 3 trials

Phase 3 trials involve large numbers of patients and assess whether a treatment is effective enough to be used more widely in the NHS.

Identifying candidates for clinical trials

The role of the COVID-19 Antivirals and Therapeutics Taskforce

The COVID-19 Antivirals and Therapeutics Taskforce works with the NIHR and other partners to horizon scan, and monitor national and international developments in COVID-19 antivirals and therapeutics.

The taskforce:

• ensures that credible or plausible candidates identified are rapidly considered for entry into UK priority platform clinical trials
• works with the RAPID C-19 collective to review the clinical evidence and, where treatments have been proven safe and effective, consider whether clinical guidance should be updated to treat UK patients

How to take part in a clinical trial

Find out if you're eligible to take part in a clinical trial on the National Institute for Health and Care Research (NIHR) website.

Putting forward treatments for entry in UK trials

Individuals from research organisations can make proposals for promising COVID-19 treatments to be considered for addition to any of the UK clinical trial platforms.

For more details about this proposals process, please contact [email protected].

See the Medicines and Healthcare products Regulatory Agency's guidance on clinical trials applications for coronavirus (COVID-19).

Current clinical platform trials for COVID-19 treatments in the UK

The NIHR established a single UK-wide process to prioritise COVID-19 research as Urgent Public Health research early in the pandemic. The purpose was to:

• prevent duplication of effort
• ensure the UK is running large enough trials to get definitive answers to key questions

The Department of Health and Social Care (DHSC) is supporting a series of national clinical trial 'platforms' across all phases of human trials and in a range of patient cohorts. These are assessing several therapeutic and prophylactic candidates, and are supported by the NIHR Clinical Research Network across the UK to identify and enrol patients.

The trial platforms are co-ordinated in a streamlined manner so that treatments can move through phase 1, 2 and 3 trials. This provides a clear route for treatments to progress rapidly from small to large-scale trials to prove safety and efficacy in treating COVID-19.

Each of the clinical trial platforms are assessing a range of potential COVID-19 treatments. Further information can be found on the individual trial websites.

AGILE

AGILE is a phase 1 and 2 clinical trial that aims to identify the safe dosage for new COVID-19 treatments, and determine whether each treatment shows evidence of a benefit beyond the standard NHS care in small patient numbers.

RECOVERY

The RECOVERY trial is the world's largest randomised controlled clinical trial for COVID-19 treatments, having recruited over 39,000 participants in its first year of running.

Participants in this trial are patients who have been admitted to hospital with moderate to severe COVID-19.

Treatments that are found to be effective in RECOVERY will be made available in the NHS to treat those with severe COVID-19 in hospital.

RECOVERY+

The RECOVERY+ trial is an extension of the larger phase 3 trial platform RECOVERY. RECOVERY+ is a phase 2 trial testing promising COVID-19 treatments for hospitalised patients.

Treatments that are successful in phase 2 trials as part of RECOVERY+ will be rapidly considered for addition to the phase 3 trials in RECOVERY to prove safety and efficacy in large patient numbers.

REMAP-CAP

REMAP-CAP is an international phase 3 trial testing treatments in patients with severe COVID-19 infection in intensive care units. Treatments that are found to be effective in REMAP-CAP will be made available in the NHS to reduce mortality and accelerate recovery in COVID-19 patients.

PRINCIPLE

PRINCIPLE is a phase 3 trial testing treatments in the community. The PRINCIPLE trial is investigating treatments that could prevent mild COVID-19 infection from becoming more serious, and participants in this trial are COVID-19 patients who have not been admitted to hospital.

If a treatment is found to be effective in PRINCIPLE, it will be made available in NHS primary care to improve health outcomes and reduce the number of patients who need to be admitted to hospital.

PROTECT-V

PROTECT-V is a phase 3 trial testing prophylactic interventions for COVID-19 in vulnerable renal and immunocompromised patients. It aims to test their effectiveness at reducing infections at events such as regular hospital check-ups or dialysis appointments.

Any treatment found to be effective as part of this platform will improve COVID-19 treatment for this vulnerable cohort of the population.

HEAL

HEAL is a phase 3 trial testing potential treatments to determine whether they can improve the longer-term outcomes for patients who have been discharged from hospital after recovering from COVID-19.

This is part of the DHSC's effort to not only ensure that patients survive but return to full health post-COVID.

STIMULATE-ICP

STIMULATE-ICP (symptoms, trajectory, inequalities and management: understanding long COVID to address and transform existing integrated care pathways) is a phase 3 trial that is currently being set up at University College London Hospitals NHS Trust.

It will be the largest long COVID trial to date, recruiting more than 4,500 people with the condition.

It will test the effectiveness of existing drugs to treat long COVID by measuring the effects of 3 months' treatment, including on people's symptoms, mental health and outcomes such as returning to work. It will also assess the use of MRI scans to help diagnose potential organ damage, as well as enhanced rehabilitation through an app to track their symptoms.

PANORAMIC

PANORAMIC is a UK-wide study sponsored by the University of Oxford and funded by the NIHR to find out in which people new community-based antiviral treatments for COVID-19 reduce the need for hospital admission and improve outcomes.

Results of trials to date: effective and ineffective treatments

In June 2020, the RECOVERY trial identified dexamethasone as the world's first effective treatment for COVID-19. Dexamethasone is now used worldwide as one of the few approved treatments for COVID-19.

Since then, there have been positive findings on tocilizumab from the REMAP-CAP and RECOVERY trials.

Effective treatments

Table 1: summary of treatments that have been found to be effective in treating COVID-19, as part of the UK clinical trial platforms

Ineffective treatments

Robust clinical trials are critical to building an evidence base of what does and does not work. It is of equal importance to reach conclusions on the ineffectiveness of potential COVID-19 treatments in order to deliver the best possible care to patients.

Table 2: summary of treatments that have been found to be ineffective in treating COVID-19, as part of the UK clinical trial platforms