Platform Adaptive trial of NOvel antiviRals for eArly treatMent of COVID-19 In the Community (PANORAMIC)

Research question Does antiviral treatment in the community safely reduce hospitalisations/deaths in symptomatic patients with confirmed COVID-19? Background Many people with COVID continue to suffer serious acute illness, with hospitalisations remaining a significant burden on the NHS. Aims and Objectives 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. 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 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. Methods 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. 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 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. 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. Timelines for Delivery 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. Impact and dissemination 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.