Award Title: Platform Adaptive trial of NOvel antiviRals for eArly treatMent of COVID-19 In the Community (PANORAMIC)
Funder: Department of Health and Social Care

Abstract: Although vaccination has dramatically reduced the chances of getting COVID and becoming very unwell with it, many people still get so ill that they do need hospital treatment. Vaccines may not protect us fully against new variants of the virus that might develop. So far, a lot of the research has been to see if medicines used to treat other conditions might also work against COVID. Now, new ‘antiviral’ drugs have been developed which act directly against the virus that causes COVID, which could help people with COVID in the community avoid severe disease and hospitalisation.  _x000D_
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Our PANORAMIC study plans to enrol people either aged 50 or over or aged 18 or over with a medical condition which makes them at higher risk of severe COVID, who have recently developed COVID symptoms, and have had a positive PCR or lateral flow test. They will be randomly assigned by a computer program to receive either standard NHS care for COVID, or one of the new antiviral drugs in addition to the usual care provided by the NHS. People across the whole of the UK will be able to join the study. _x000D_
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Our main question will be whether these new antiviral treatments safely help people with COVID-19 avoid the need for hospital admission. We will also test whether these drugs:  _x000D_
Shorten the length of time that people have symptoms of COVID _x000D_
Reduce the chance that people living with someone who has COVID also catches it _x000D_
Lessen the amount of the virus we shed when we are infected, _x000D_
Are affected by new variants or changes in the virus once we start using them _x000D_
Offer value for money to the NHS _x000D_
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Our team has learned a lot from running the PRINCIPLE study; the world’s largest and most successful community-based trial looking at which existing drugs improve COVID symptoms and reduce the need for hospital admission. So far we have tested five different drugs in PRINCIPLE and nearly 6000 people with COVID have taken part. In this new PANORAMIC trial, we will build on our experience in PRINCIPLE by including more expertise from around the UK to make our study design more suited to testing new drugs, analysing viral samples, assessing value for money, and including patient representatives from diverse and disadvantaged backgrounds to deliver a world-leading study of novel treatments for COVID in the community. Findings will improve evidence supporting treatment for COVID world-wide.

Lay Abstract: Research question _x000D_
Does antiviral treatment in the community safely reduce hospitalisations/deaths in symptomatic patients with confirmed COVID-19? _x000D_
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Background _x000D_
Many people with COVID continue to suffer serious acute illness, with hospitalisations remaining a significant burden on the NHS.  _x000D_
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Aims and Objectives _x000D_
PANORAMIC’s primary objective is to assess effectiveness of novel antiviral treatment(s) in safely reducing all cause hospitalisation and/or death within 28 days from randomisation, in high-risk patients with a confirmed PCR positive SARS-CoV-2 test result in the community.  The main secondary outcomes will be return to full-function, prevention of severe disease, reduction in symptoms, speed of recovery, including among clinically vulnerable groups.  _x000D_
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A Viral Load Sub-Study will investigate the impact of antivirals on viral load, time to virus clearance and an assessment of potential for development of resistance under drug selective pressure _x000D_
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A Post-exposure Prophylaxis Sub-Study will determine how effective the antiviral is in preventing the transmission of SARS-CoV-2 when given to household contacts of index cases who have given consent. _x000D_
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Methods _x000D_
PANORAMIC will have UK-wide reach. A master protocol will govern the platform trial with a Bayesian analytic approach. All enrolment (screening, informed consent, eligibility review and baseline data) and follow-up procedures (daily diary, data capture of hospitalisations and deaths) can be performed and captured online on the trial website or by telephone with a member of the trial team.  _x000D_
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Adults aged 18 or above who are clinically vulnerable and clinically extremely vulnerable, or aged 50 and above, with a positive SARS-COV-2 PCR test or positive lateral flow test and symptoms of COVID-19 illness starting within the previous 5 days will be eligible. They will complete screening and informed consent online or by phone with a member of the trial team and be randomised to receive usual NHS care or an antiviral plus usual NHS care. Antivirals will be delivered directly to the participant using urgent courier. Participants will be asked daily whether they feel recovered by text, phone or email, for 28 days, and follow-up at 3 and 6 months for assessment of longer-term effects. _x000D_
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Hospitalisation and deaths will be captured either patient report or by NHS Digital data extracts. Recovery will be patient reported. Safety will be closely monitored appropriate to the stage of development of each agent and availability existing data, with capacity for an intensive monitoring and sampling phase followed by potential graduation to a remote monitoring phase.  _x000D_
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Timelines for Delivery _x000D_
The University of Oxford University has demonstrated capacity for efficiently and effectively sponsoring national platform trials. Using our established broad approach, we plan to start on September 1st, 2021 with the first patient randomised within one or two months, with first findings out in 18 months. _x000D_
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Impact and dissemination  _x000D_
PANORAMIC will uniquely expand the evidence about the effectiveness of novel antivirals to benefit COVID patients in the NHS and worldwide. Results will be rapidly disseminated through pre-prints, publications and notification on the trial website, as well as direct to the MHRA, Antiviral Task Force, NICE, the WHO, and guideline developers world-wide.

Research Activity Codes: 6.1 PHARMACEUTICALS
Health Categories: INFECTION