In the general community, people over 60 years of age and people with co-morbidities including hypertension, cardiovascular disease, lung disease, cancer, diabetes and chronic liver disease are at greater risk of poorer outcomes with COVID-19 illness(2-6). The Australian Government Department of Health has advised that Aboriginal and Torres Strait Islander people 50 years and older, with one or more chronic medical conditions, may be at greater risk of serious COVID-19 illness. Hence people with chronic hepatitis B who are older and/or have co-morbidities are also likely to be at greater risk of having poorer outcomes with the COVID-19 illness.

Measures to optimise these patients’ health should include supporting smoking cessation, optimising diabetic and blood pressure control. We currently recommend not ceasing or switching away from ACE inhibitors or angiotensin receptor blocker medications: there is not enough evidence that these agents increase the risk of worse outcomes of COVID-19 illness(7) and ceasing or switching these agents may cause harm to otherwise stable patients.  Other key measures include encouraging appropriate exercise, maintaining regular appointments via Telehealth or face-to- face if required, streamlining dispensing of scripts and blood slips, supplying supporting documents for financial assistance and actively referring and encouraging patients to attend Telehealth appointments with medical and allied health specialists. Clinicians should encourage patients to consider Advance Care Planning, as discussed in a recent paper on the clinical presentation and management of COVID-19(8).

  • Australia and New Zealand are actively involved in designing research studies that address the COVID-19 illness that occurs following infection with SARS-CoV-2  
  • Several clinical trials have been registered in Australasia that are designed to look at the prevention and treatment benefits of diverse therapeutic agents including a vaccine study  
  • Several observational studies, including a study of immunosuppressed populations, neonatal outcomes, a biobanking study and a study of the role of physiotherapy in intensive care are underway to help characterise the COVID-19 illness and its sequelae 
  • Several studies are looking at the psychological impact of the COVID-19 pandemic on healthcare workers and the general population 
  • Two registries have been established  to look at the impact of COVID-19 illness upon cardiac function and pregnancy outcomes  
  • People living with blood borne viruses are eligible for several studies 
  • Recently published data are available that address the safety and efficacy of remdesivir and hydroxychloroquine for treatment of COVID-19 illness 

 

Australia and New Zealand are actively involved in research that addresses the COVID-19 illness that occurs following infection with SARS-CoV-2.  Of these, those that have been registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR)(2) and/or the United States ClinicalTrials.gov(3) have been selectively summarised in Table 1.  For information on other registered studies not listed in Table 1 and for daily updates on new COVID-19 studies refer to ANZCTR(2), ClinicalTrials.gov(3) and the WHO COVID-19 Clinical Trials Registry(4). 

Some of the treatment and prevention studies listed in Table 1 indicate that people living with HIV are eligible for enrolment: HIV positive people are eligible for the REMAP-COVID study and the ASCOT treatment studies, but in the ASCOT study only participants who are on antiretroviral therapy are eligible; HIV positive people are not eligible for the DAS 181 study, the BCG study, or the MEND study. People living with hepatitis B and hepatitis C are not eligible for the MEND study. People living with untreated hepatitis B and primary or secondary immunodeficiency are not eligible for the Tocilizumab study. People living with HIV, hepatitis B or hepatitis C are not eligible for the Novavax vaccine study. 

 

Name & Sponsor & Trail number

Intervention

Number (N) & Design & Note if eligibility statement provided regarding people living with blood borne viruses

Sites

Noted to be Open 

PREVENTION of COVID-19

 

 

 

 

Evaluation of the Safety and Immunogenicity of a SARS-CoV-2 rS (COVID-19) Nanoparticle Vaccine With/Without Matrix-M Adjuvant 

 

Novavax 

 

NCT04368988 

 

Phase 1 

2 IM injections at a 21-day interval (Day 0 and Day 21) of: 

NSS Saline Placebo 

versus 

SARS-CoV-2 rS - 25 μg without Matrix-M 

versus 

SARS-CoV-2 rS - 5 μg with 50 μg Matrix-M 

versus 

SARS-CoV-2 rS - 25 μg with 50 μg Matrix-M 

versus 

SARS-CoV-2 rS - 25 μg with 50 μg Matrix-M followed by Placebo 

N=131 

 

A phase I/II blinded, randomised, placebo controlled trial 

 

People with HIV, hepatitis B and hepatitis C are excluded 

Victoria 

Queensland 

Yes

Effectiveness of Prophylactic Hydroxychloroquine on incidence of COVID-19 infection in Front-line Health and Allied Health Care Workers: The COVID-SHIELD Trial 

Walter and Eliza Hall Institute of Medical Research 

ACTRN12620000501943p 

 

Hydroxychloroquine orally once daily; 400mg (>=65kg body weight) or 200mg (<65kg body weight) for 4 months 

 

versus 

 

placebo once daily for 4 months 

N=2250  

 

Blinded randomised controlled trial 

 

People with immunosuppressive conditions, or medications (sic) are excluded 

Victoria, South Australia, New South Wales, Australian Capital Territory 

No

BCG Vaccination to Protect Healthcare Workers Against COVID-19. The BRACE study. 

 

Murdoch Research Children’s Institute 

 

NCT04327206 

 

Single dose BCG 0.1ml 

N= 4,170 

 

Open label, phase 3 randomised controlled trial 

 

HIV positive people excluded because of risk of dissemination BCG infection  

 

Victoria, 

Western Australia, 

South Australia 

Yes

Chloroquine RepurpOsing to healthWorkers for Novel CORONAvirus 

mitigaTION  

(CROWN CORONA) 

 

Washington University School of Medicine 

 

NCT04333732 

Low-dose (300mg chloroquine base weekly) 

 

versus 

 

Medium-dose (300mg chloroquine base twice weekly)  

 

versus 

 

High-dose (150 mg chloroquine base daily) 

 

versus 

 

placebo 

N=55,000 

 

Bayesian, adaptive, pragmatic, participant level randomisation, international, placebo-controlled trial 

 

Randomization will be stratified by age (<50 and ≥50) and study site 

Victoria 

No

Multi-Site, Randomized, Open-Label, Parallel-Group, Placebo-Controlled Study to Assess the Chemoprophylactic Efficacy of Chloroquine Against SARS-CoV-2/COVID-19 in Healthcare Workers at High-Risk of Exposure 

 

Australian Defence Force Malaria and Infectious Disease Institute 

 

ACTRN12620000417987 

 

Oral 500mg chloroquine phosphate tablets prophylactic weekly regimen against COVID-19 over 10 week trial period  

 

versus 

 

Vitamin C placebo 

 

P

N= 680 

 

Multi-Site, Randomized, Open-Label, Parallel-Group, Placebo-Controlled Study  

 

Queensland 

 

 

Yes

Treatment

 

 

 

 

International ALLIANCE Study of Therapies to Prevent Progression of COVID-19 

 

National Institute of Integrative Medicine, Australia 

Catholic Health Initiatives 

 

NCT04395768 

 

Participants will be randomized to azithromycin, hydroxychloroquine, zinc, Vitamin D3/B12 and IV Vitamin C for 14 days 

 

Versus 

 

Azithromycin, zinc and hydroxychloroquine, Vitamin D3/B12 for 14 days 

N=200 

 

Open label, randomised controlled trial 

Adaptive design 

Not stated 

 

 The MEND (MEseNchymal coviD-19) Trial: a pilot study to investigate early efficacy of mesenchymal stem cells in adults with COVID-19. The MEND trial. 

 

Cynata Therapeutics Limited 

 

ACTRN12620000612910 

 

DAS181 for 7 or 10 days

(For the COVID-19 substudy)

Mesenchymoangioblast-derived mesenchymal stem cells (CYP-001) at a dose of 2 million cells/kg (up to a maximum of 200 million cells) by IV infusion on two occasions (Day 1 and Day 3) PLUS standard of care in ICU 

 

versus 

 

Standard of care in ICU 

New South Wales 

No

Tocilizumab for the treatment of COVID-19 in intensive care patients: effect on days free of ventilatory support. 

 

QIMR Berghofer Medical Research Institute 

 

ACTRN12620000580976p 

 

Patients in the intensive care setting will be randomized 2:1 to receive a single dose of intravenous 400mg Tocilizumab plus standard of care in ICU 

 

Versus 

 

Standard or care in ICU 

N=150 

 

Open label randomised controlled trial 

 

Patients with untreated hepatitis B and primary and secondary immunodeficiency are excluded 

Queensland 

No

BEAT COVID-19: A Phase III Bayesian adaptive randomisation platform controlled trial to evaluate the efficacy of drug interventions for COVID-19 on hospital admission or death in the community setting for high risk older people 

 

University of Sydney 

 

ACTRN12620000566932p 

 

Initial treatment will be hydroxychloroquine 200mg bd for 7 days 

 

versus 

 

Placebo i bd for 7 days 

N=3000 

 

Blinded randomised placebo controlled trial 

New South Wales 

No

Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia  (REMAP-CAP) 

 

REMAP-COVID is a sub-platform of REMAP-CAP 

 

MJM Bonten 

 

NCT02735707 

REMAP-COVID will include the following drugs in the comparator arms: 

-Lopinavir-ritonavir 

-Hydroxychoroquine 

-Lopinavir-ritonavir plus Hydroxychoroquine 

- Interferon-β1a 

- Anakinra (interleukin1 receptor antagonist) 

- Tocilizumab 

- Sarilumab 

Phase 4, randomised, embedded, multifactorial, adaptive platform trial  

New South Wales, 

Northern Territory, 

Queensland, South Australia, Victoria, Western Australia 

Yes 

Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia  (REMAP-CAP

 

REMAP-COVID is a sub-platform of REMAP-CAP 

 

MJM Bonten 

 

NCT02735707 

 

REMAP-COVID will include the following drugs in the comparator arms: 

-Lopinavir-ritonavir 

-Hydroxychoroquine 

-Lopinavir-ritonavir plus Hydroxychoroquine 

- Interferon-β1a 

- Anakinra (interleukin1 receptor antagonist) 

- Tocilizumab 

- Sarilumab 

Phase 4, randomised, embedded, multifactorial, adaptive platform trial  

New South Wales, 

Northern Territory, 

Queensland, South Australia, Victoria, Western Australia 

Yes

Australasian COVID-19 Trial (ASCOT). A multi-centre randomised clinical trial to assess clinical, virological and immunological outcomes in patients with SARS-CoV-2 infection (COVID-19) treated with lopinavir/ritonavir and/or hydroxychloroquine compared to standard of care 

 

University of Melbourne 

 

ACTRN12620000445976 

-Lopinavir-ritonavir  

versus 

- Hydroxychloroquine 

 versus 

- Lopinavir-ritonavir plus hydroxychloroquine  

versus 

- standard  care 

N= 2,500 

 

Phase 3, randomized open, controlled trial 

 

HIV positive people are excluded if they are not on antiretroviral therapy 

All States and Territories and New Zealand 

Yes 

Cord Blood Therapy to prevent progression of COVID-19 related pneumonia 

 

Monash Health 

 

ACTRN12620000478910 

 

Intravenous umbilical cord blood  

 

versus  

 

standard care 

 

N= 24 

 

Randomised controlled trial 

Victoria 

No

A Phase III Randomized Placebo-Controlled Study to Examine the Efficacy and Safety of DAS181 for the Treatment of Lower Respiratory Tract Parainfluenza Infection in Immunocompromised Subjects 

  

(Substudy: DAS181 for COVID-19) 

 

Ansun Biopharma, Inc. 

 

NCT03808922 

 

DAS181 for 7 or 10 days  

(For the COVID-19 substudy) 

N= 250 

 

International, randomised controlled study 

 

HIV positive subjects are excluded 

 

 

New South Wales, 

Queensland, 

Victoria 

Yes

A Randomised, Double Blind, Placebo-Controlled Trial of the Efficacy of Hydroxychloroquine for the Community-Based Treatment of Adults With Diagnosed COVID-19 

 

Medical Research Institute of New Zealand 

 

ACTRN12620000457943p 

 

Hydroxychloroquine  

 

versus  

 

placebo for five days 

N= 70 

 

Blinded, randomised placebo- controlled trial 

New Zealand 

No

High-dose intravenous zinc (HDIVZn) as adjunctive therapy in COVID-19 positive critically ill patients: A pilot randomized controlled trial 

 

Austin Hospital, Victoria 

 

ACTRN12620000454976 

 

Intravenous zinc chloride for 7 days  

 

versus  

 

intravenous normal saline placebo daily for 7 days 

N= 160 

 

Blinded randomised controlled trial 

 

HIV positive subjects are excluded 

Victoria 

No

EXPANDED ACCESS TREATMENT TRIALS 

 

 

 

 

Expanded Access Treatment Protocol: Remdesivir (RDV; GS-5734) for the Treatment of SARS-CoV2 (CoV) Infection 

 

Gilead Sciences 

 

NCT04323761 

 

Intravenous remdesivir 

N= not stated 

 

Open label access study 

Victoria, 

New South Wales 

 

Yes

RESEARCH PLATFORMS & BIOBANKS 

 

 

 

 

 

 

Covid-19 Biobank: a clinical database and biological bank of clinical samples from individuals with COVID-19 infection to better characterise the clinical course and pathogenesis of the infection and provide insights into potential therapeutic agents

 

Alfred Hospital

 

ACTRN12620000609954

 

N/A

N=250

 

There are no exclusion criteria

Victoria

Yes

OBSERVATIONAL STUDIES

 

 

 

 

ADAPT - COVID-19 Study - Characterizing pathophysiological, immunological and clinical outcomes relating to COVID-19 infection in the patient population of St Vincent’s Hospital Sydney

 

St Vincent’s Health Network

 

ACTRN12620000554965

 

 

 

N/A

N=300

 

Prospective, observational cohort study of all patients at St Vincent’s Hospital Sydney who test positive for COVID-19 infection. The cohort will consist of two components.
Cohort A - Mild disease patients recruited through the community cohorts
Cohort B - Moderate-severe patients recruited via St Vincent’s Hospital Sydney

 

New South Wales

No

Coronavirus Outcomes Registries in Immunocompromised Individuals Australia (CORIA): a Multisite Registry and Optional Biorepository in People With COVID-19 and Selected Conditions Affecting Immune Function

 

Kirby Institute

 

NCT04354818

 

N/A

N=1000

 

Prospective observational cohort study of immunosuppressed patients with COVID-19

 

HIV positive subjects are eligible

 

New South Wales

No

Loss of SMELL as an earlY marker in patients with COVID-19. The SMELLY study

 

Royal North Shore Hospital

 

ACTRN12620000575932

 

 

N/A

N=100

 

Observational study

 

The prevalence of olfactory dysfunction in patients with COVID-19 will be determined using the validated University of Pennsylvania Smell Identification Test (UPSIT).

 

New South Wales

Yes

Recovery of Patients From COVID-19 After Critical Illness (COVID-Recovery)

 

Australian and New Zealand Intensive Care Research Centre

 

 

NCT04401254

 

 

N/A

N=300

 

Prospective observational study of the physiotherapy interventions provided to patients with COVID-19 admitted to the ICU and health outcomes

 

Victoria

No

Neonatal CoVID-19 Study to evaluate the population health impacts of COVID-19 in mothers and their newborn infants cared for in tertiary and non-tertiary hospitals in Australia.

 

Hunter New England LHD

 

ACTRN12620000527965

 

 

N/A

N=1000

 

Prospective observational study of COVID-19 confirmed infants or infants born to COVID-19 confirmed mothers

 

 

 

All States and Territories

No

PSYCHOLOGICAL STUDIES

 

 

 

 

Randomised controlled trial of an app-based intervention, Anchored, to support the mental health of Australians recently unemployed due to COVID-19.

 

University of New South Wales

 

ACTRN12620000555954

 

Randomised to use ‘Anchored’ a smartphone app

 

versus

 

Being placed in a waitlist group and being provided with support referral services

N=492

 

Randomised controlled trial

All States and Territories

No

Psychological impact of COVID-19 pandemic on perioperative staff at the Royal Melbourne Hospital – a longitudinal study

 

Royal Melbourne Hospital

 

ACTRN12620000590965p

N/A

N= 90

 

Prospective observational study

Royal Melbourne Hospital, Victoria

No

Stress-reduction Using Probiotics to Promote Ongoing Resilience Throughout COVID-19 for Healthcare Workers: A randomised placebo-controlled trial

 

University of Auckland

 

ACTRN12620000480987p

 

Daily capsules containing either the probiotic Lactobacillus rhamnosus HN001 for 12 weeks

 

versus

 

a placebo for 12 weeks

 

N=507

 

Randomised controlled trial

New Zealand

No

Impact of Social Isolation on Mental Health during the COVID-19 Pandemic: a large international multi-centre cohort study

 

The George Institute for Global Health

 

ACTRN12620000479909p

 

Not applicable

N= 3,000

 

International observational study

 

 

All States and Territories

No

Randomised Controlled Trial of Problem Management Plus versus Enhanced Treatment as Usual, on Anxiety and Depression in People Distressed by Covid 19

 

UNSW

 

ACTRN12620000468921p

 

Problem Management Plus

Comprising 6 x 60 minutes sessions via teleconference

 

versus

 

Referral to portal with stress coping strategies

N= 140

 

Blinded randomised controlled trial

NSW

No

Home telerehabilitation for people with COVID-19: Implementing telehealth approaches to care and its effect on reintegration into the community

 

Flinders Medical Centre

 

ACTRN12620000443998p

 

Telerehabilitation using a Coaching model

 

versus

 

a traditional model for 11 sessions

N=58

 

Blinded, randomised controlled trial

South Australia

No

REGISTRIES

 

 

 

 

Angiotensin II Infusion in COVID-19-Associated Vasodilatory Shock: A multinational, multicentre registry

 

Rinaldo Bellomo, Austin Health

 

ACTRN12620000620921

 

 

 

 

Not applicable

N= 315

 

Patients admitted to ICU with COVID-19 who are, or who are not treated with angiotensin II and other novel therapies will be enrolled in the registry retrospectively and prospectively

New South Wales,

Victoria

No

AUSTRALIAN CARDIOVASCULAR COVID-19 REGISTRY (AUS-COVID)

 

Royal North Shore Hospital

 

ACTRN12620000486921

 

Not applicable

Patients admitted to hospital with confirmed SARS-CoV-2 infection will be enrolled in the registry will

New South Wales,

Queensland, South Australia, Victoria, Western Australia

 

No

Prospective registry of maternal, perinatal and neonatal outcomes from pregnancies infected with SARS-COV2 (COVID-19)

 

University of Melbourne

 

ACTRN12620000449932

Not applicable

N=200

 

Observational study

 

All States and Territories

No

 

 

BCG 

The Bacille Calmette-Guérin vaccine, in addition to its role in preventing infection with Mycobacterium tuberculosis, has immunomodulatory properties and is used for this purpose to induce an immune response against tumour cells in non-invasive bladder cancer.  As noted in a recent commentary by Dr Nigel Curtis(5) who is leading the Australian COVID-19 BCG study listed in Table 1, BCG has been shown to induce memory in the innate immune system and reduce mortality beyond its role in the prevention of tuberculosis(6).  

 

Chloroquine  

Chloroquine is an anti-malarial drug. In vitro data from a recent study showed that low concentrations of chloroquine blocked SARS-CoV-2 infection in Vero E6 cells(7). Chloroquine is known to block infection with the first SARS virus, SARS-CoV, by changing the pH of cells’ endosomes and by interfering with the glycosylation of SARS-CoV receptors(8).  There has been a brief publication that referred to 15 COVID-19 treatment trials in China, which stated that chloroquine was effective in treating over 100 people(9), however the contents of this publication has been met with caution(10).  

 

Hydroxychloroquine 

Hydroxychloroquine is a metabolite of chloroquine and is used to treat a number of autoimmune disorders. Two French studies examined the impact of hydroxychloroquine on the PCR positivity of nasopharyngeal swabs for SARS-CoV-2.  

An open-label study undertaken in Paris reported that when hydroxychloroquine was combined with azithromycin for treatment of 11 patients consecutively admitted to hospital with COVID-19 illness, PCR assays from nasopharyngeal swabs remained positive for 5-6 days following commencement of treatment (11). This was in contrast to findings of a study undertaken in Marseille of patients hospitalised with COVID-19, which reported that at day 6, 70% of 20 patients treated with hydroxychloroquine +/- azithromycin had negative nasopharyngeal swabs versus only 12.5% of the 16 controls(12). However, as summarised by Ferner(10) concerns about this study included that the findings from six patients’ in the treatment arm were not evaluated (12).  

 

There has been one randomised study from China which examined both viral clearance and clinical outcomes in 30 patients hospitalised with COVID-19 illness(13). This study reported no difference in PCR positivity of pharyngeal swabs at day 7 between those randomised to receive five days of hydroxychloroquine versus standard treatment and no difference in clinical outcomes(13).   

 

The Marseille study team recently reported on a retrospective study on 1061 people with symptomatic or asymptomatic SARS-CoV-2 infection who were treated with combination hydroxychloroquine and azithromycin for 10 and 9 nine days, respectively. The authors concluded that the treatment was safe with 2.3% reporting adverse events; QT prolongation was observed in nine patients but no arrhythmias, cardiac events or sudden deaths occurred. The authors noted that good clinical outcome and virological clearance was observed in 91.7% of patients(14).  

 

Results were released recently from a large international registry study of 96, 032 hospitalised patients with COVID-19, which examined the association between in-hospital mortality and treatment with hydroxychloroquine, or chloroquine either alone or with a macrolide antibiotic (15). There were 14, 888 patients who received these treatments and 81,144 patients who did not and served as the control group. The authors found that use of either of these drugs either alone or with a macrolide was associated with decreased in-hospital survival and an increased risk of clinically significant cardiac arrhythmias when compared to controls.  Most importantly this study was not a randomised controlled trial. Since its release there have been concerns raised regarding the study’s recruitment methodology and its statistical analysis(10). Following this study’s publication the World Health Organisation instructed that there be a ‘temporary pause’ of the hydroxychloroquine arm in the WHO Solidarity trial(11).  

 

In Australia, the ASCOT study is waiting for further data to become available and the study remains open and the COVID SHIELD study remains open.  

 

Lopinavir-ritonavir 

Lopinavir is a protease inhibitor of HIV-1 and has in vitro activity against SARS-CoV(16). In a recent randomised controlled study of 199 patients hospitalised with COVID-19 illness, there was no difference in time to clinical improvement or discharge from hospital between participants who were randomised to 14 days of treatment with lopinavir-ritonavir versus standard care(17).  

 

Anakinra, Tocilizumab and Sarilumab 

Use of these agents represent a therapeutic approach to the management of the cytokine disturbance that occurs in COVID-19 illness, including in some cases, the cytokine storm syndrome (CSS)(18). Anakinra is a recombinant human receptor IL-1 antagonist and as summarized by Cron and Chatham(19), has been used for treatment of CSS. Tocilizumab is an anti-IL-6 monoclonal antibody and has been used for the treatment of CSS including in the setting of COVID-19 illness, as reported in one small, single-centre study(20). Sarilumab is a monoclonal antibody that binds and blocks the IL-6 receptor.  

 

DAS181 

DAS181 is a recombinant sialidase fusion protein, which removes sialic acid receptors that are present on the host’s respiratory epithelial cells, thereby preventing viruses from binding to these host receptors. It has activity against a number of influenza viruses, as reviewed by Koszalka et al(21). 

 

Umbilical cord blood 

It has been postulated that the mesenchymal stem cells present in umbilical cord blood may help improve the innate immune response in the setting of COVID-19 illness(22). One small study from China has reported on seven patients who received mesenchymal stem cells(23). 

 

Remdesivir 

Remdesivir is a prodrug of a nucleotide analogue and is metabolised within cells to become an analogue of adenosine triphosphate; it inhibits RNA polymerases and has in vitro activity against several viruses including SARS-CoV-2. Remdesivir was registered in Australia in May 2020 for an expanded access treatment trial for people with COVID-19 illness.  

 

In early April 2020 data from a small cohort study with 53 evaluable patients who were hospitalised with severe COVID-19 and received at least one dose of remdesivir were reported(24). The authors reported 18% mortality in ventilated patients and 5% mortality in non-ventilated patients over a median follow-up of 18 days(24).  

 

Recently results were released from a large, blinded randomised controlled trial of remdesivir versus placebo in patients hospitalised with COVID-19 illness(25). The study’s primary outcome was time to recovery, which was defined as discharge from hospital, or being kept in hospital solely for infection control purposes. Patients were randomized according to disease severity and study site. Results from 1089 randomised patients found a significantly shorter time to discharge for those who received remdesivir (11 days (95% confidence Interval [CI] 9-12)) versus placebo (15 days, (95% CI 13-19)). The participants whose baseline disease severity was that they required only supplemental oxygen appeared to benefit the most from remdesivir, compared to those with milder or more severe disease; this may be explained by the fact that this disease severity group had the highest number of patients. At day 14, mortality was 7.1% for remdesivir and 11.9% for placebo (hazard ratio for death, 0.70; 95%CI, 0.47-1.4).   Serious adverse events occurred in 114 and 141 of remdesivir and placebo recipients, respectively; only 2 events in each arm were attributed to study drug or placebo(25). The authors concluded that the study’s findings support remdesivir’s use for hospitalised patients requiring supplemental oxygen.   

 

Importantly the authors noted the findings of a smaller blinded, randomised controlled trial conducted in 10 hospitals in Wuhan, China, which was published in late April 2020(26). Interestingly, the majority of participants’ baseline disease severity in this study was that they required supplemental oxygen. However, this trial did not find that remdesivir led to faster clinical improvement compared to placebo. Of note, the study was stopped prematurely because the epidemic had waned in Wuhan and the authors noted that the study was underpowered, having required 453 patients to demonstrate benefit from remdesivir, but having enrolled only 237 patients(26). 

 

Finally a randomised open-label study of 397 patients hospitalised with COVID-19 pneumonia was published in late May 2020(27). Study participants were randomised to receive remdesivir for either five or ten days and the study’s primary endpoint was the participants’ clinical status at day 14. The authors did not find a difference in efficacy between the five and ten day courses of remdesivir, but noted that these findings could not be applied to critically ill patients on mechanical ventilation because only approximately 3% of study participants were mechanically ventilated(27).  

Table 

  1. National COVID-19 Clinical Evidence Taskforce https://covid19evidence.net.au/. 
  2. Australian New Zealand Clinical Trials Registry https://anzctr.org.au/TrialSearch.aspx - &&conditionCode=&dateOfRegistrationFrom=&interventionDescription=&interventionCodeOperator=OR&primarySponsorType=&gender=&distance=&postcode=&pageSize=20&ageGroup=&recruitmentCountryOperator=OR&recruitmentRegion=&ethicsReview=&countryOfRecruitment=Australia%7cNew+Zealand&registry=&searchTxt=COVID+19+OR+%22SARS-CoV2%22+OR+%222019-nCoV%22&studyType=&allocationToIntervention=&dateOfRegistrationTo=&recruitmentStatus=&interventionCode=&healthCondition=&healthyVolunteers=&pa. 
  3. ClinicalTrials.gov https://clinicaltrials.gov/ct2/results?cond=COVID&term=&cntry=AU&state=&city=&dist= 
  4. WHO International Clinical Trials Registry Platform https://www.who.int/ictrp/search/en/ 
  5. Curtis, N. 2019. BCG Vaccination and All-Cause Neonatal Mortality. Pediatr Infect Dis J 38: 195-197. 
  6. Higgins, J. P., K. Soares-Weiser, J. A. Lopez-Lopez, A. Kakourou, K. Chaplin, H. Christensen, N. K. Martin, J. A. Sterne, and A. L. Reingold. 2016. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ 355: i5170. 
  7. Wang, M., R. Cao, L. Zhang, X. Yang, J. Liu, M. Xu, Z. Shi, Z. Hu, W. Zhong, and G. Xiao. 2020. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30: 269-271. 
  8. Vincent, M. J., E. Bergeron, S. Benjannet, B. R. Erickson, P. E. Rollin, T. G. Ksiazek, N. G. Seidah, and S. T. Nichol. 2005. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2: 69. 
  9. Gao, J., Z. Tian, and X. Yang. 2020. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 14: 72-73. 
  10. Ferner, R. E., and J. K. Aronson. 2020. Chloroquine and hydroxychloroquine in covid-19. BMJ 369: m1432. 
  11. Molina, J. M., C. Delaugerre, J. Le Goff, B. Mela-Lima, D. Ponscarme, L. Goldwirt, and N. de Castro. 2020. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Med Mal Infect. 
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