CADTH COVID News identifies emerging information on health technologies being investigated for the management or prevention of COVID-19.  The intent is to provide a quick alert of a news item of interest and is only current as of posting. As research is rapidly evolving, CADTH will monitor these topics and update information as needed.


Updated on September 29, 2020 | 3:00pm

Remdesivir

CADTH assessed four randomized controlled trials as part of a health technology review on remdesivir. On August 21, 2020, the results of the phase III, international, multi-centre, open-label, randomized controlled GS-US-540-5774 study were published that compared patients with moderate COVID-19 who received remdesivir (five-day course or 10-day course), with standard of care alone.  The odds of improvement in clinical status at day 11 was statistically significantly higher in the five-day remdesivir group compared with the standard of care group (odds ratio = 1.65; 95% confidence interval 1.09 to 2.48, P = 0.02). However, there was no statistical difference in the odds of improvement in clinical status between the 10-day remdesivir group compared with standard of care. CADTH will continue to monitor the emerging evidence related to remdesivir in COVID-19.

Updated on July 30, 2020 | 4:37pm

Remdesivir is an antiviral medication that is the first drug approved by Health Canada for COVID-19. This decision was issued on July 27, 2020 and is an authorization with conditions to prescribe remdesivir for the treatment of COVID-19 in patients with pneumonia who require oxygen therapy. CADTH assessed four randomized controlled trials as part of a health technology review on remdesivir and will continue to monitor the emerging evidence related to remdesivir in COVID-19.


COVID-19 Vaccines: Government of Canada Announcement

Updated on September 28, 2020 | 5:35pm

On September 25, 2020, the Government of Canada announced a new agreement to secure up to 20 million doses of the COVID-19 vaccine candidate AZD1222, which is being developed by AstraZeneca. This agreement adds to five previous ones that have been put in place to establish a guaranteed supply of potential COVID-19 vaccines for Canadians: the protein subunit vaccine candidate by Sanofi and GlaxoSmithKline (up to 72 million doses); Ad26.COV2.S by Johnson & Johnson (up to 38 million doses); NVX-CoV2373 by Novavax (up to 76 million doses); BNT162 by Pfizer (up to 20 million doses); and mRNA-1273 by Moderna (up to 56 million doses). Clinical trials are still underway to evaluate the efficacy and safety of these vaccines for the prevention of COVID-19, and Health Canada regulatory approval will be required for each vaccine before it is made available to Canadians.

Updated on August 14, 2020 | 3:45pm

On August 5, 2020, the Government of Canada announced that it has entered into two agreements to secure a future supply of COVID-19 vaccines. An agreement has been made with Pfizer for its BNT162 mRNA-based vaccine candidate and another agreement has been made with Moderna for its mRNA-1273 vaccine candidate. While all potential vaccine candidates will require Health Canada regulatory approval before they are available to Canadians, this move establishes a guaranteed supply of millions of doses of the two previously mentioned vaccines for COVID-19. The government has indicated that other negotiations, investments, and procurement plans are underway.


Updated on September 23, 2020 | 4:55pm

Tocilizumab

On September 18, 2020, a press release was made available about the results of a study of tocilizumab for the treatment of COVID-19 (EMPACTA, NCT04372186). A multi-centre, randomized, double-blind, placebo-controlled trial that compared tocilizumab to placebo (in addition to standard of care) for the treatment of patients hospitalized with COVID-19 pneumonia was conducted. There were 389 patients enrolled from the US, South Africa, Kenya, Brazil, Mexico, and Peru. The primary end point — progression to mechanical ventilation or death by day 28 — occurred in 12.2% in the tocilizumab arm versus 19.3% in the placebo arm. The hazard ratio was 0.56; 95% confidence interval: 0.32 to 0.97. There was no statistically significant difference between the groups for time to hospital discharge, time to improvement, time to clinical failure, or mortality. Common adverse events reported included constipation, anxiety, and headache. Until the full study results are published in a peer-reviewed journal, no conclusions can be drawn from this information.

Updated on September 9, 2020 | 11:16am

CADTH completed a Health Technology Review on tocilizumab, and will continue to monitor the emerging evidence related to this drug for managing COVID-19.

Updated on July 27, 2020 | 13:30pm

Tocilizumab, an interleukin-6 receptor antagonist, is indicated for cytokine release syndrome and for various rheumatological disorders in Canada. A phase III international trial, COVACTA (including Canadian sites) is under way investigating tocilizumab compared to placebo in patients with COVID-19 (NCT04320615). Randomized controlled trials are ongoing and CADTH will continue to monitor the emerging evidence related to interleukin-6 receptor antagonists in COVID-19.


Updated on September 9, 2020 | 11:18am

Sarilumab

CADTH completed a Horizon Scan on sarilumab, and will continue to monitor the emerging evidence related to this drug for managing COVID-19.

Updated on July 27, 2020 | 13:30pm

Sarilumab is an interleukin-6 receptor antagonist indicated for rheumatoid arthritis in Canada and has been identified as a potential option to treat COVID-19. On July 2, 2020, the phase III cohort 2 (NCT04315298) of patients with COVID-19 that required mechanical ventilation failed to meet primary and key secondary end points and the trial was stopped. There are ongoing randomized controlled trials investigating sarilumab monotherapy versus placebo or standard of care for the treatment of COVID-19. CADTH will continue to monitor emerging evidence related to interleukin-6 receptor antagonists in COVID-19.


Updated on September 8, 2020 | 15:35am

Azithromycin

Azithromycin is a macrolide antibiotic indicated in Canada to treat bacterial infections, such as community acquired pneumonia or skin infections. On September 4, 2020, a multicentre, open-label randomized controlled trial was published comparing azithromycin (oral or intravenous) plus standard of care to standard of care alone (including hydroxychloroquine) for 447 patients hospitalized with COVID-19 in Brazil who required nasal oxygen at 4 L/min, high flow oxygen or mechanical ventilation. There was no statistically significant difference between the treatment groups in terms of the primary outcome of the clinical status at 15 days post randomization. There are ongoing trials investigating azithromycin for the treatment of COVID-19. CADTH will continue to monitor the emerging evidence related to azithromycin in managing COVID-19.


Updated on September 4, 2020 | 11:05am

Systemic Corticosteroids

On September 2, 2020, the results of three randomized controlled trials examining the effect of systemic corticosteroids for the treatment of severe COVID-19 were published: the CAPE-COVID trial, the CoDEX trial, and the REMAP-CAP COVID-19 corticosteroid domain trial. In addition, a prospective meta-analysis of seven randomized controlled trials (including the three new trials and the RECOVERY trial) was published. The authors of the meta-analysis concluded that for critically ill patients with COVID-19, the use of systemic corticosteroids was associated with lower 28-day all-cause mortality when compared to placebo or usual care. WHO released a living guidance document that currently provides a strong recommendation for the use of systemic corticosteroids for the treatment of patients with severe and critical COVID-19. At this time, Health Canada recommends that clinicians strongly consider the use of intravenous dexamethasone (or an equivalent glucocorticoid dose) for patients who have COVID-19 and require oxygen or mechanical ventilation. CADTH will continue to monitor the emerging evidence related to corticosteroids in managing COVID-19.


Updated on September 2, 2020 | 12:15pm

Interferon Beta-1b

Interferon Beta-1b is an immunomodulator indicated in Canada for the treatment of multiple sclerosis. On August 24, 2020, the results of a study on interferon beta-1b for the treatment of COVID-19 were published. The study was a small open-label, single-centre, randomized controlled trial that compared standard of care with standard of care plus interferon beta-1b for the treatment of patients hospitalized with severe COVID-19 in Iran. There were 80 patients randomized, but data are presented for the 66 patients who completed the trial. The primary end point — median time to clinical improvement (two-point improvement on a six-point ordinal scale) — was nine days (interquartile range six days to 10 days) in the interferon group plus standard of care versus 11 days in the standard of care group (interquartile range nine days to 15 days) respectively, P = 0.002, hazard ratio = 2.30; 95% confidence interval: 1.33 to 3.39. CADTH will continue to monitor the emerging evidence related to interferon beta-1b in managing COVID-19.


Updated on September 1, 2020 | 12:55pm

Interferon Beta-1a

Interferon beta-1a is an immunomodulator indicated in Canada for the treatment of multiple sclerosis. On August 20, 2020, a small, single-centre (Iran), open-label randomized controlled trial was published comparing interferon beta 1a to standard of care for patients hospitalized with COVID-19. There was no statistical difference between the treatment groups in terms of the primary outcome of the time to clinical response. There are ongoing trials investigating different types of interferons for the treatment of COVID-19. CADTH will continue to monitor the emerging evidence related to interferon beta-1a in managing COVID-19.


Updated on August 25, 2020 | 10:45am

Convalescent Plasma

On August 19, 2020, the FDA’s plan to issue an emergency authorization for convalescent plasma to treat COVID-19 was put on hold due to emerging data. However, the FDA has now (on August 23, 2020) issued an emergency use authorization (EUA) for investigational convalescent plasma to treat patients hospitalized with suspected or laboratory-confirmed COVID-19. Although clinical trials on the efficacy and safety of convalescent plasma for the treatment of COVID-19 remain ongoing, the FDA’s EUA is based on an extensive review of available evidence and is meant to facilitate emergency access to convalescent plasma treatment for patients with COVID-19.

Lopinavir-ritonavir

CADTH has completed a Health Technology Review on lopinavir-ritonavir and will continue to monitor the emerging evidence related to this drug combination for managing COVID-19


Updated on August 24, 2020 | 3:30pm

Chloroquine and Hydroxychloroquine

CADTH has completed a Health Technology Review on chloroquine and hydroxychloroquine and will continue to monitor the emerging evidence related to these drugs for managing COVID-19.

Favipiravir

CADTH has completed a Horizon Scan on Favipiravir and will continue to monitor the emerging evidence related to this drug for managing COVID-19.


Updated on August 21, 2020 | 3:35pm

Convalescent Plasma

On August 19, 2020, it was reported that the FDA’s plan to issue an emergency authorization for convalescent plasma to treat COVID-19 has been put on hold. This decision was reportedly based on emerging data from a study involving patients hospitalized with severe COVID-19, who were participating in a US-based Expanded Access Program (n = 35,322). In this study (currently released in preprint), the authors reported that plasma transfusion within three days of a COVID-19 diagnosis was associated with lower seven-day and 30-day mortality rates compared with plasma transfusion four or more days after a COVID-19 diagnosis. However, this study was not randomized and has not been peer-reviewed. In Canada, access to convalescent plasma is currently only available through participation in clinical trials and is the responsibility of Canadian Blood Services and Héma-Québec. CADTH has conducted a Technology Review of convalescent plasma for COVID-19 and will update this report on a monthly basis as data continue to emerge.


 

Updated on August 13, 2020 | 1:33pm

Hydroxychloroquine

On July 23, 2020, the results of a study on hydroxychloroquine for the treatment of COVID-19 were published. The study was an open-label, multi-centre randomized controlled trial that compared standard of care, hydroxychloroquine plus standard of care, and hydroxychloroquine with azithromycin plus standard of care for the treatment of patients hospitalized with suspected or confirmed COVID-19 in Brazil (n = 667). There was no statistically significant difference between the groups in terms of the primary outcome of clinical status at day 15; however, there were more adverse effects (including prolonged QT interval and elevated liver enzymes) in the hydroxychloroquine groups. CADTH will continue to monitor the emerging evidence related to hydroxychloroquine or chloroquine in managing COVID-19.


Updated on July 27, 2020 | 1:30pm

Favipiravir

Favipiravir is an oral antiviral drug that has emerged as a potential treatment or prevention option for COVID-19. An international expert panel issued a weak recommendation for not using favipiravir in patients with non-severe or severe COVID-19 because of low-quality evidence. Researchers in Canada plan to conduct a randomized controlled trial evaluating the efficacy of favipiravir compared with placebo for adults living in long-term care homes focused on controlling COVID-19 outbreaks (NCT04448119). Favipiravir is not approved in Canada and is not currently accessible outside of clinical trials. CADTH will continue to monitor emerging evidence related to antiviral agents in COVID-19.

Lopinavir-Ritonavir

The co-formulation of lopinavir-ritonavir is an antiretroviral drug indicated for the treatment of HIV-1 in Canada. There are published and ongoing randomized controlled trials investigating lopinavir-ritonavir to potentially manage COVID-19. On June 29, 2020, the RECOVERY study Steering Committee discontinued randomization in the lopinavir-ritonavir treatment arm based on no benefit. On July 4, 2020, the Solidarity Trial established by WHO discontinued the lopinavir-ritonavir treatment arm due to a lack of efficacy. CADTH will continue to monitor emerging evidence related to antiretroviral drugs in COVID-19.

Dexamethasone

On July 17, 2020, the preliminary results of the RECOVERY study were published comparing dexamethasone plus usual standard of care with usual standard of care alone. The RECOVERY study is a large, ongoing, multi-centre, open-label, randomized controlled trial investigating several treatments for patients hospitalized with COVID-19. CADTH has conducted a critical appraisal of the published results and will continue to monitor the emerging evidence related to systemic corticosteroids in managing COVID-19.