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

Autor: Thomas Snelling, Marjoree Sehu, Asha Bowen, Naomi Hammond, Dominica Zentner, James Molton, David Paterson, Katie Flanagan, David Price, Ayesha Verrall, Megan Rees, Bala Venkatesh, James McMahon, Andrew John Burke, Kumar Visvanathan, Vivekanand Jha, Justin Denholm, Gail Matthews, Bradley Gardiner, Roberta Littleford
Jazyk: angličtina
Rok vydání: 2020
Předmět:
medicine.medical_specialty
Blinding
Letter
hydroxychloroquine
viruses
Medicine (miscellaneous)
Lopinavir/ritonavir
law.invention
03 medical and health sciences
0302 clinical medicine
Randomized controlled trial
law
immune system diseases
Intensive care
General & Internal Medicine
medicine
Pharmacology (medical)
030212 general & internal medicine
protocol
1102 Cardiorespiratory Medicine and Haematology
Randomised controlled trial
lcsh:R5-920
business.industry
virus diseases
COVID-19
Lopinavir
Hydroxychloroquine
1103 Clinical Sciences
biochemical phenomena
metabolism
and nutrition
ASCOT Investigator Group
Clinical trial
Coronavirus
lopinavir
ritonavir
Cardiovascular System & Hematology
Relative risk
Emergency medicine
business
lcsh:Medicine (General)
030217 neurology & neurosurgery
medicine.drug
Zdroj: Trials
Trials, Vol 21, Iss 1, Pp 1-3 (2020)
ISSN: 1745-6215
Popis: 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 treatment allocation. No unblinding procedures relating to potential adverse effects are therefore required. Numbers to be randomised (sample size) We assumed that 5% of participants receiving standard of care would meet the primary outcome, aimed to evaluate whether interventions could lead to a relative risk of 0.5, assuming no interaction between intervention arms. This corresponds to a required sample size of 610 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 2440. Trial Status ASCOT protocol version 3, May 5, 2020. Recruitment opened April 4, 2020 and is ongoing, with planned completion of enrolment July 31, 2021. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12620000445976). Prospectively registered April 6, 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
Databáze: OpenAIRE
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