The Australasian COVID-19 Trial (ASCOT) to assess clinical outcomes in hospitalised patients with SARS-CoV-2 infection (COVID-19) treated with lopinavir/ritonavir and/or hydroxychloroquine compared to standard of care: A structured summary of a study protocol for a randomised controlled trial

The Australasian COVID-19 Trial (ASCOT) to assess clinical outcomes in hospitalised patients with SARS-CoV-2 infection (COVID-19) treated with lopinavir/ritonavir and/or hydroxychloroquine compared to standard of care: A structured summary of a study protocol for a randomised controlled trial

Content Partner: Lincoln University. Objectives: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. Trial...

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Hauptverfasser: Denholm, JT, Davis, J, Paterson, D, Roberts, J, Morpeth, S, Snelling, T, Zentner, D, O'Sullivan, M, Price, D, Bowen, A, Tong, SYC, Denholm, J, Anderson, S, McQuilton, Z, Venkatesh, B, Hammond, N, Jha, V, Burston, VJ, McMahon, J, Charles, P, Commons, R, O'Brien, D, Mahoney, A, Sheffield, D, Lim, LL, Gardiner, B, Schulz, T, Torresi, J, Chean, R, Sasadeusz, J, Aboltins, C, Singh, K, Yong, M, Lister, D, Molton, J, Tai, A, Chalmers, R, Martinello, M, Wilson, P, Coghill, S, Foo, H, Sud, A, Williams, J, Lwin, N, Post, J, Van Haal, S, Sullivan, R, Matthews, G, Kwan, BCH, Slack, A, Shum, O, Cochrane, B, Dotel, R, Gilbey, T, Mina, M, Su, Y, Trethewy, C, Hudson, B, Chatterji, A, New, D, Raby, E, Hui, S, Robinson, O, Hart, J, Tan, SJ, Chambers, J, Rafiei, N, Smith, S, Sehu, M, Da Silva, J, Griffin, P, Henderson, A, Chaw, K, Choong, K, Burke, A, Heather, C, Senanayake, S, Boyd, M, Anagnostou, M, Trad, A, Ratcliff, A, Dummer, J, Bhally, H, Giola, M, Grimwade, K, Chang, CLL, Verrall, A, Hogg, S, Restropo, D, Maze, M, Ritchie, S, Gedye, C, Chang, J, Pillai, P, Flanagan, K, Mora, J, Lam, E, Littleford, R, Knoblauch, N, Slow, Sandra-Marie
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Zusammenfassung:Content Partner: Lincoln University. Objectives: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. Trial design: ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management. Participants: Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently. Intervention and comparator: Participants will be randomised 1:1:1:1 to: Group 1: standard of care; Group 2: lopinavir (400mg) / ritonavir (100mg) twice daily for 10 days in tablet form; Group 3: hydroxychloroquine (800mg) 4x200mg administered 12 hours apart on Day 1, followed by 400mg twice a day for 6 days; Group 4: lopinavir /ritonavir plus hydroxychloroquine. Main outcomes: Proportion of participants alive and not having required intensive respiratory support (invasive or non-invasive ventilation) at 15 days after enrolment. A range of clinical and virological secondary outcomes will also be evaluated. Randomisation: The randomisation schedule will be generated by an independent statistician. Randomisation will be stratified by site and will be in permuted blocks of variable block size. The randomised sequence allocation will only be accessible to the data management group, and site investigators will have individual participant allocation provided through a web-based trial enrolment platform. Blinding (masking): This is an open-label study, with researchers assessing the laboratory outcomes blinded to treatm