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

Abstract

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.

Biology of COVID-19 and related viruses: Epidemiology, signs, symptoms, diagnosis, and treatment

“…Conversely, in a more recent double-blind, randomized trial, hydroxyquinoline did not prevent infection when used as postexposure prophylaxis [ 117 ]. There are currently ongoing clinical trials to elucidate hydroxyquinoline’s effectiveness against COVID-19 [ [118] , [119] , [120] ].…”

Hydroxychloroquine for coronavirus: how not to repurpose a drug during a pandemic

“…On the other side, multiple conspiracy theories were promiscuously attached to chloroquine as a passing vehicle to carry old grievances into public attention regardless of truth. Large RCT including those sponsored by WHO (SOLIDARITY), in the United Kingdom (RECOVERY) and in Australia (ASCOT), inserted hydroxychloroquine treatment arms into their adaptive designs 7–9 . Several post‐exposure prophylaxis (PEP) or pre‐exposure prophylaxis (PreP) studies were planned.…”

“…A planned adaptive platform trial (ASCOT) incorporating 80 sites throughout Australia and New Zealand faced challenges of securing multisite agreements and approvals within a rapid timeframe coupled with a paucity of eligible cases (due to effective initial public health measures in both countries) and the aforementioned interruption following the retracted Lancet study 7 . On 30 July, it discontinued its hydroxychloroquine arm, citing lack of equipoise in light of international RCT findings, without having enrolled a single participant.…”

“…Large RCT including those sponsored by WHO (SOLIDARITY), in the United Kingdom (RECOVERY) and in Australia (ASCOT), inserted hydroxychloroquine treatment arms into their adaptive designs. [7][8][9] Several post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PreP) studies were planned. By July, over 200 clinical trials utilising chloroquine or hydroxychloroquine had been registered worldwide.…”

COVID ‐19 response: the perspectives of infectious diseases physicians and clinical microbiologists

“…Reflecting the current lack of clear data about therapeutic options for patients with COVID‐19, over three‐quarters (169, 79%) of infectious diseases physicians felt they had equipoise for a clinical trial of specific antiretroviral. We advocate for investigational agents for COVID‐19 to only be used in the context of a clinical trial 5 . At this time of great challenge to the Australian and New Zealand health care systems, infectious diseases physicians and microbiologists stand with all health care professionals and members of the community.…”