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 January 25, 2022 | 2:00pm
Remdesivir (Veklury)
On January 21, 2022, the US FDA revised the authorization for remdesivir to allow its use in non-hospitalized patients. Based on the PINETREE study (NCT04501952), the new indication is for the treatment of mild to moderate COVID-19 in non-hospitalized adults and adolescents (12 years of age and older who weigh at least 40 kg) with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who are at high risk for progression to severe COVID-19. Remdesivir should be given within 7 days of symptom onset and administered as an IV infusion of 200 mg on day 1 followed by 100 mg on day 2 and day 3 (total treatment duration of 3 days).
The US FDA also expanded the emergency use authorization of remdesivir to include non-hospitalized children (those weighing 3.5 kg to less than 40 kg or those younger than 12 years of age weighing at least 3.5 kg) with mild-to-moderate COVID-19 with laboratory-confirmed SARS-CoV-2 who are at high risk for progression to severe COVID-19. The dose of remdesivir is based on weight: 5 mg/kg on day 1 followed by 2.5 mg/kg on day 2 and day 3 for children weighing 3.5 kg to less than 40 kg (total of 3 days of treatment).
In Canada, remdesivir is indicated for the treatment of COVID-19 in adults and adolescents (aged 12 years and older with body weight at least 40 kg) with pneumonia requiring supplemental oxygen. It is not approved for children.
Updated on January 20, 2022 | 2:30pm
Remdesivir (Veklury)
On January 19, 2022, the Canadian Treatments for COVID-19 (CATCO) group published the findings of an open-label randomized controlled trial conducted in 52 Canadian hospitals (NCT04330690) as part of the WHO’s Solidarity study. The trial compared remdesivir plus standard of care (634 patients) to standard of care alone (648 patients) in hospitalized adults with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Remdesivir was administered at an initial dose of 200 mg IV on day 0 followed by 100 mg IV daily on days 1 to 9. In-hospital mortality, the primary outcome, was 18.7% (117 patients) in the remdesivir group compared with 22.6% (145 patients) for the standard of care group (relative risk = 0.83; 95% confidence interval, 0.67 to 1.03). In Canada, remdesivir received a Notice of Compliance with Conditions on July 27, 2020. It is indicated for the treatment of COVID-19 in adults and adolescents with pneumonia requiring supplemental oxygen. CADTH published an implementation advice on October 15, 2020.
Updated on January 17, 2022 | 5:05pm
Nirmatrelvir and Ritonavir (Paxlovid)
On January 17, 2022, Health Canada issued a Notice of Compliance with Terms and Conditions for Paxlovid, an oral antiviral medication that combines nirmatrelvir (PF-07321332), a selective inhibitor of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CL protease, and ritonavir, a pharmacoenhancer. The treatment is indicated for the treatment of mild-to-moderate COVID-19 in adults with a laboratory-confirmed diagnosis of SARS-CoV-2 infection and who are at high risk for progression to severe COVID-19, including hospitalization or death. The authorization is based on the results of the EPIC-HR study (NCT04960202).
Updated on January 12, 2022 | 2:30 pm
Ensovibep (MP0402)
Ensovibep is a DARPin (Designed Ankyrin Repeat Proteins) antiviral drug. EMPATHY (NCT04828161) is an ongoing phase II/III, multi-centre, randomized, double-blind trial that compares a single IV dose of ensovibep to placebo.
Results for part A (phase II) of the EMPATHY study were released on January 10, 2022. A total of 407 ambulatory (vaccinated and unvaccinated) adults with at least 2 mild to moderate symptoms of COVID-19, with a COVID-19 diagnosis confirmed by PCR, were randomized to receive 1 of 3 doses of ensovibep: 75 mg, 225 mg, or 600 mg or placebo. The primary end point was met with a statistically significantly reduction in viral load over 8 days compared to placebo. There was a 78% risk reduction of hospitalization and/or emergency room visits related to COVID-19, or death across treated groups (4 of 301 patients [1.3%]) compared to placebo (6 of 99 patients [6.0%]). Part B (phase III) of EMPATHY will further evaluate the 75 mg dose of ensovibep in an additional 1,700 patients. Caution should be exercised in interpreting results reported in a press release, until further details are available in the peer reviewed literature.
Updated on December 10, 2021 | 12:05pm
Tixagevimab and Cilgavimab (AZD7442)
The drugs tixagevimab and cilgavimab were authorized for emergency use in the US on December 8, 2021. The FDA authorization is based on primary data from PROVENT (NCT04625725), an ongoing phase III randomized, double-blind, placebo-controlled trial. The drugs, which are co-packaged under the brand name Evusheld, are used in the prevention of COVID-19. Specifically, they are indicated for pre-exposure prophylaxis of COVID-19 in adults and adolescents (aged 12 and older who weigh 40 kg or more) who are moderately to severely immunocompromised due to a medical condition or a medication and may have an inadequate immune response to a COVID-19 vaccination, as well as for those for whom a COVID-19 vaccination is contraindicated. It is further specified that those who are currently infected with SARS-CoV-2 or have had a recent known exposure to a person infected with SARS-CoV-2 are not candidates for this product. Tixagevimab 150 mg and cilgavimab 150 mg are administered intramuscularly as one dose in 2 separate consecutive injections. This product is currently under review by Health Canada.
Updated on August 25, 2021 | 11:45am
AZD7442
AZD7442 ― a drug that combines 2 long-acting antibodies (tixagevimab [AZD8895] and cilgavimab [AZD1061]) ― is in clinical development for both the prevention and treatment of COVID-19. PROVENT (NCT04625725) is a phase III, randomized, double-blind, placebo-controlled multi-centre trial evaluating AZD7442 as a pre-exposure prophylaxis of COVID-19, with results published in a press release on August 20, 2021. AZD7442 administered as a single 300 mg dose was compared to placebo in 5,197 unvaccinated adult patients randomized in a 2:1 ratio. The primary efficacy outcome was the incidence of symptomatic COVID-19. AZD7442 statistically significantly reduced the risk of developing symptomatic COVID-19 by 77% (95% CI, 46 to 90) compared with placebo. CADTH included this drug in a Horizon Scan completed in December 2020. Caution should be exercised in interpreting results reported in a press release.
Updated on October 29, 2021 | 1:00pm
Fluvoxamine
Fluvoxamine is a selective serotonin reuptake inhibitor approved by Health Canada to treat depression and obsessive-compulsive disorders. The TOGETHER study (NCT04727424), published in The Lancet on October 27, 2021, reported the effectiveness of the early use of fluvoxamine in community patients with COVID-19. High-risk symptomatic adults with confirmed SARS-CoV-2 from 11 centres in Brazil were enrolled in this phase III, placebo-controlled, double-bind, randomized, adaptive platform trial. In addition to standard of care, patients received oral fluvoxamine 100 mg twice daily for 10 days (741 patients) or placebo (756 patients). The composite primary outcome was the need for hospitalization, defined as either retention in a COVID-19 emergency setting or transfer to a tertiary hospital due to COVID-19 within 28 days of randomization. In the fluvoxamine group, 79 (11%) patients had a primary outcome event compared with 119 (16%) in the placebo group (relative risk = 0.68; 95% Bayesian credible interval, 0.52 to 0.88), with a probability of superiority of 99.8% for the intention-to-treat population. There were no significant differences between fluvoxamine and placebo for time to hospitalization (P = 0.11), number of days in hospital (P = 0.06), mortality (P = 0.24), time to death (P = 0.49), or number of days on mechanical ventilation (P = 0.90). This is an adaptive trial, and 1,826 patients were assigned to other treatments (ivermectin, doxazosin, peginterferon lambda, or peginterferon beta); the trial is ongoing for these treatments.
Updated on October 28, 2021 | 10:00am
Opaganib
Opaganib (ABC294640), a selective inhibitor of sphingosine kinase-2, is in clinical development for the treatment of moderate to severe COVID-19 pneumonia. The results of a phase IIa, multi-centre, randomized, double-blind, placebo-controlled trial (NCT04414618) on the use of opaganib for COVID-19 pneumonia were published online in a pre-print. A total of 42 hospitalized patients who required supplemental oxygen received oral opaganib 500 mg every 12 hours (n = 23) or placebo (n = 19) for 14 days; both groups also received standard of care. The primary outcome measure was total supplemental oxygen requirement. At day 14, 11 patients (50.0%) in the active group no longer required supplemental oxygen for at least 24 hours compared with 4 patients (22.2%) in the placebo group. This trial is limited by its small sample size, and the results have not yet undergone peer review.
On October 4, 2021, the results from a phase II/III, multi-centre, randomized, double-blind, placebo-controlled trial (NCT04467840) on opaganib treatment for COVID-19 pneumonia were reported in a press release. The study included 475 hospitalized patients with severe COVID-19 pneumonia on supplemental oxygen; the data presented were from a post hoc analysis of 251 patients with moderately severe COVID-19 who required a fraction of inspired oxygen up to 60% at baseline. For the primary outcome, 77.0% of patients treated with opaganib were switched to room air by day 14 compared with 63.5% of patients treated with placebo (nominal P value = 0.033). It was also reported that patients treated with opaganib had a statistically significant reduction in mortality compared with patients treated with placebo (7 deaths in 117 patients versus 21 deaths in 134 patients, respectively; nominal P value = 0.019; relative risk = 2.6). Caution should be exercised in interpreting post hoc analyses and results reported in a press release.
Updated on September 14, 2021 | 16:00pm
Anakinra, an Interleukin-1 Receptor Antagonist
On September 3, 2021, a phase III trial was published describing the final results of an interleukin-1 receptor antagonist, anakinra, for the treatment of hospitalized patients with moderate or severe COVID-19 at risk of progressing to respiratory failure. The SAVE-MORE trial is a pivotal, phase III, confirmatory, randomized, double-blind multi-centre study. This study enrolled 594 adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and plasmasuPAR of 6 ng/mL or greater (a biomarker that is thought to predict risk in those with COVID-19)(NCT04680949). The primary outcome of the study was assessed by the 11-point WHO Clinical Progression Scale (WHO-CPS) on day 28. The final analysis results showed that the odds of improvement in clinical status on the 11-point WHO-CPS were higher with anakinra than placebo at day 28 (adjusted proportional odds ratio = 0.36, 95% confidence interval, 0.26 to 0.50).
Updated on September 1, 2021 | 17:30am
Heparin
Two studies published in the New England Journal of Medicine on August 26, 2021 reported the findings of using heparin in critically ill and in non-critically ill patients hospitalized with severe or moderate COVID-19, respectively. The 2 studies arose from the integration of 3 multi-centre, open-label, adaptive, randomized controlled trials ― REMAP-CAP (NCT02735707), ACTIV-4 (NCT04505774, NCT04359277), and ATTACC (NCT04372589) ― for which the eligibility criteria, interventions, outcome measures, and data collection were prospectively aligned.
Patients were randomized to a therapeutic dose of heparin (intravenous unfractionated heparin or subcutaneous low molecular weight heparin) or usual-care thromboprophylaxis (low or moderate dose of a thromboprophylactic drug). The critically ill population included 1,207 patients and the non-critically ill population included 2,219 patients. The primary outcome was organ support–free days at day 21 evaluated on an ordinal scale. Death during hospitalization through 90 days was assigned the worst possible score of –1.
In the critically ill population, the trial was stopped early because of futility. A therapeutic dose of heparin did not result in a greater number of days free of organ support compared to usual-care pharmacologic thromboprophylaxis in patients with severe COVID-19.
In the non-critically ill population, the probability that the therapeutic-dose heparin increased organ support–free days compared with usual-care thromboprophylaxis was 98.6% (median-adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). Of 1,171 patients receiving the therapeutic dose of heparin, 939 (80.2%) survived until hospital discharge without receipt of organ support during the first 21 days compared with 801 of 1,048 patients (76.4%) in the usual-care group (median-adjusted absolute difference, 4.0%; 95% credible interval, 0.5 to 7.2).
Updated on August 25, 2021 | 11:35am
Sotrovimab (VIR-7831)
Sotrovimab was authorized under an Interim Order by Health Canada on July 30, 2021. It is indicated to treat mild to moderate COVID-19 in adults and adolescents (12 years of age and older weighing at least 40 kg) who are at high risk for progressing to hospitalization and/or death. Sotrovimab is administered as a single 500 mg intravenous dose infused over the course of 1 hour.
Updated on May 28, 2021 | 10:35am
On May 26, 2021, sotrovimab (VIR-7831) was granted an Emergency Use Authorization by the FDA based on the results of COMET-ICE, the COVID-19 Monoclonal antibody Efficacy Trial — Intent to Care Early. The authorization is for adults and children (12 years of age and older weighing at least 40 kg) with mild to moderate COVID-19 who are at high risk for progression to severe COVID-19, including hospitalization or death. The drug is currently under review by Health Canada.
Updated on August 25, 2021 | 11:30am
Molnupiravir
Molnupiravir (EIDD-2801, MK-4482) is a broad-spectrum anti-viral drug with activity against severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2. The results of a phase IIa, randomized, placebo-controlled trial was published in a pre-print in June 2021 (NCT04405570). A total of 204 adult outpatients in 10 centres in the US with confirmed SARS-CoV-2 infection and symptom onset within 7 days were included in the trial. They were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 mg or 800 mg) or placebo, twice-daily for 5 days. The primary efficacy outcome was time to viral ribonucleic acid clearance, which was significantly reduced in participants receiving 800 mg of molnupiravir (median: 14.0 days [95% confidence interval, 13.0 to 14.0]) compared to those who were administered a placebo (median: 15.0 days [95% confidence interval, 15.0 to 27.0]; log-rank P-value = 0.013). Secondary outcomes included measuring viral ribonucleic acid change, the severities and durations of self-reported COVID-19 symptoms, and safety. Molnupiravir is currently under review by Health Canada.
Updated on August 25, 2021 | 10:30am
Plonmarlimab (TJM2 or TJ003234)
Plonmarlimab is a neutralizing antibody that targets granulocyte-macrophage colony-stimulating factor. It is currently in clinical development to evaluate its use in the treatment of cytokine release syndrome in severe COVID-19 patients. The results of an interim analysis of a phase II/III, randomized, double-blind, placebo-controlled multi-centre study conducted in the US (NCT04341116) are available in a press release. The primary efficacy outcome is the proportion of participants alive and free of mechanical ventilation. It reports that 83.6% of patients receiving plonmarlimab versus 76.7% in the placebo group were free of mechanical ventilation by day 30. The mortality rate was 4.9% and 13.3% in the plonmarlimab and placebo groups, respectively, by day 30. Plonmarlimab is not approved in Canada and caution should be exercised in interpreting interim results published in a press release.
Updated on June 29, 2021 | 13:00pm
Tocilizumab
On June 24, 2021, the US FDA issued an emergency use authorization for tocilizumab to treat hospitalized adults and children (2 years of age and older) with COVID-19. The authorization is for those who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. Tocilizumab is not approved to treat COVID-19 in Canada. A CADTH review on tocilizumab was published in March 2021.
Updated on June 17, 2021 | 15:00pm
Casirivimab-Imdevimab
Health Canada has authorized the use of combination product casirivimab-imdevimab, both monoclonal antibodies, by Interim Order on June 9, 2021. It is indicated to treat mild to moderate COVID-19 in adults and adolescents (aged 12 years and older weighing at least 40 kg) with confirmed SARS-CoV-2 infection at high risk for hospitalization and/or death. Casirivimab 1,200 mg and imdevimab 1,200 mg are administered together as a single intravenous infusion. CADTH has previously published an evidence review on casirivimab-imdevimab.
Updated on May 31, 2021 | 16:50pm
Regdanvimab (CT-P59)
Regdanvimab is a virus-neutralizing monoclonal antibody under review by Health Canada. The European Medicines Agency issued an advice in March of 2021 with a recommendation that it be used to treat adult patients with confirmed COVID-19 who do not require supplemental oxygen for COVID-19 and who are at high risk of progressing to severe COVID-19. Pre-clinical data have shown that regdanvimab has neutralizing potency against emerging severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, variants including those from New York (B.1.526), Nigeria (B.1.525), and India (B.1.617). While there are no completed or published trials, there is one ongoing phase II/III clinical trial. CADTH included this drug in a Horizon Scan completed in December 2020.
Updated on March 15, 2021 | 12:35pm
Monoclonal antibody, VIR-7831
On March 10, 2021, a press release was issued describing the interim results of a monoclonal antibody, VIR-7831, as monotherapy for the early treatment of COVID-19 in non-hospitalized patients. The COVID-19 Monoclonal Antibody Efficacy Trial – Intent to Care Early (COMET-ICE) is a phase III, ongoing, randomized, double-blind, placebo-controlled multi-centre study. This study enrolled adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and with oxygen saturation of 94% or more, who were randomized to receive either VIR-7831 or placebo (NCT04545060). Based on interim results from 583 patients that demonstrated an 85% reduction in the primary end point of hospitalization or death among patients who were administered VIR-7831 in comparison to placebo (P = 0.002), the independent data safety monitoring committee recommends stopping COMET-ICE early. Caution should be exercised in interpreting any interim results. CADTH will continue to monitor emerging evidence related to monoclonal antibodies in COVID-19.
Updated on April 14, 2021 | 16:05pm
Inhaled Budesonide for Community Use in Patients With COVID-19 at Risk for Adverse Outcomes
PRINCIPLE is an ongoing, multi-centre, open-label, multi-arm, adaptive platform randomized controlled trial (ISRCTN86534580) evaluating various interventions, including inhaled budesonide, in non-hospitalized patients aged 65 years or older, or 50 years or older with comorbidities, who have confirmed or suspected COVID-19 and ongoing symptoms. An interim analysis, published as a pre-print, included patients with confirmed severe acute respiratory syndrome coronavirus 2 (or SARS-CoV-2) infections, with 751 patients randomized to usual care and inhaled budesonide 800 mcg twice daily for 14 days, and 1,028 patients randomized to usual care alone. The co-primary outcomes were time to self-reported recovery and incidence of hospitalization or death due to COVID-19 within 28 days. Patients in the budesonide group had a statistically significantly shorter time to recovery compared with patients in the usual care group. While there were less hospitalizations or deaths with budesonide, the results were not statistically significant. Caution should be exercised in interpreting any interim results published in a pre-print.
Updated on April 1, 2021 | 12:20pm
Monoclonal Antibody, Leronlimab
On March 23, Health Canada received an application for leronlimab under its interim order for COVID-19 and it is currently under review. The US FDA granted CytoDyn Inc. Emergency Investigational New Drug (EIND) status for leronlimab for COVID-19. NCT04347239 is a phase IIb/III, two-arm, randomized, double blind, placebo-controlled, multi-centre study that enrolled adult patients who were hospitalized with severe or critical illness caused by COVID-19 to receive either weekly doses of 700 mg leronlimab or placebo, subcutaneously. The primary end point is all-cause mortality at 28 days. Results based on 309 patients in the modified intention-to-treat population reported in a press release on March 30, 2021 indicated a 6.5% absolute risk reduction in death at day 28 for patients administered leronlimab compared to placebo, in addition to other COVID-19 treatments (P = 0.0319). Caution should be exercised in interpreting any preliminary results. CADTH will continue to monitor emerging evidence related to monoclonal antibodies as related to COVID-19.
Updated on April 1, 2021 | 11:20am
Lenzilumab for COVID-19 pneumonia
A phase III trial of lenzilumab (a GM-CSF monoclonal antibody) has been completed and results are available in a news release. The multi-centre, randomized, double-blind, placebo-controlled trial (NCT04351152) enrolled 520 hospitalized patients with severe and critical COVID-19 pneumonia. All patients received standard of care remdesivir or dexamethasone, or both. Results were positive for lenzilumab for the primary end point of ventilator-free survival after 28 days. The manufacturer will be seeking an emergency use authorization from the US FDA. CADTH will continue to monitor this drug.
Updated on March 30, 2021 | 16:20pm
Interleukin-6 Receptor Antagonists: Tocilizumab and Sarilumab
In a Health Technology Review on tocilizumab and sarilumab, CADTH assessed 11 randomized controlled trials, including the preliminary results from the RECOVERY trial preprint.
Updated on February 23, 2021 | 16:55am
CADTH has completed a Health Technology Review on tocilizumab and sarilumab, and will update this report with preliminary results from the RECOVERY trial preprint.
Updated on January 15, 2021 | 15:55am
On January 7, 2021, preliminary results on the efficacy of interleukin-6 receptor antagonists in critically ill patients with COVID-19 were released in a pre-print (NCT02735707). The Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (REMAP-CAP) is an ongoing international, open-label trial that enrolled patients with COVID-19 in an intensive care unit and receiving respiratory or cardiovascular organ support randomized to either tocilizumab (N = 353) or sarilumab (N = 48) or standard care (N = 402). The primary outcome was respiratory and cardiovascular organ support-free days measured up to day 21. Compared with standard care, the median adjusted odds ratios (primary model) were 1.64 (95% credible interval 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval 1.17 to 2.91) for sarilumab, yielding > 99.9% and 99.5% posterior probabilities of superiority. Caution should be exercised in interpreting any preliminary study results. Furthermore, this pre-print has not been peer-reviewed.
On December 17, 2020, results of the phase III, randomized, double-bind, placebo-controlled, multi-centre study EMPACTA (Evaluating Minority Patients with Actemra) were published (NCT04372186). The EMPACTA study enrolled hospitalized patients with COVID-19 pneumonia not receiving mechanical ventilation who underwent randomization to standard care plus tocilizumab (N = 259) or placebo (N = 129). The primary efficacy outcome was mechanical ventilation or death by day 28. The hazard of death was lower in the standard care plus tocilizumab group compared to placebo (hazard ratio 0.56, 95% confidence interval 0.33 to 0.97).
A CADTH technology review on interleukin-6 receptor therapies in managing COVID-19 is in progress.
Updated on March 1, 2021 | 4:10pm
WHO Solidarity Study: Remdesivir
CADTH assessed 5 randomized controlled trials, including the interim study results from WHO Solidarity, in a health technology review on remdesivir
Remdesivir
Updated on March 1, 2021 | 4:10pm
CADTH assessed 5 randomized controlled trials, including the interim study results from WHO Solidarity, in a health technology review on remdesivir
Updated on February 11, 2021 | 13:35pm
FDA Grants Emergency Use Authorization for Bamlanivimab and Etesevimab Combination Treatment
On February 9th, the US FDA issued an Emergency Use Authorization (EUA) for the combination of 2 monoclonal antibodies — bamlanivimab and etesevimab — for the treatment of “mild to moderate COVID-19 in adults and pediatric patients (12 years of age or older weighing at least 40 kilograms) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization.” The EUA is based on findings from the BLAZE-1 randomized controlled trial (NCT04427501). The trial demonstrated that treatment with the combination of bamlanivimab and etesevimab, compared to placebo, was associated with a statistically significant reduction in the primary end point of severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2, viral load at 11 days (between-group difference, ‒0.57, 95% confidence interval, ‒1.00 to ‒0.14, P = 0.01). It should be noted that the EUA does not extend to patients who are hospitalized or require oxygen therapy because of COVID-19. The FDA previously issued an EUA for bamlanivimab for the treatment of mild to moderate COVID-19. In Canada, bamlanivimab alone has been authorized with conditions for the treatment of mild to moderate COVID-19.
Updated on February 10, 2021 | 15:50pm
Azithromycin
On February 2, 2021, Lancet published the results of the RECOVERY Trial (NCT04381936) pertaining to azithromycin. RECOVERY is a UK-based, multi-centre (176 hospitals), randomized, controlled, open-label, adaptive platform trial with multiple treatment arms, each being compared with usual care. While the dexamethasone, hydroxychloroquine, lopinavir–ritonavir, convalescent plasma, and tocilizumab groups have now been stopped, the trial is on-going for REGN-COV2, Aspirin, and colchicine. In this recent publication, 7,763 hospitalized patients with COVID-19 were randomized to usual care (5,181 patients), or usual care with azithromycin 500 mg daily orally, or intravenously for 10 days, or until discharge (2,582 patients). The median duration of treatment with azithromycin was 6 days (interquartile range of 3 days to 10 days). There was no statistically significant difference between the 2 groups for the primary end point of 28-day all-cause mortality (rate ratio 0.97; 95% confidence interval 0.87 to 1.07, P value = 0.50). Furthermore, there was no statistically significant difference between the 2 groups for any of the secondary outcomes including duration of hospital stay and the proportion of patients discharged from hospital within 28 days. Hence, this trial has stopped the enrolment of patients into this treatment arm.
Updated on January 27, 2021 | 9:40pm
SARS-CoV2 Neutralizing Antibody: Bamlanivimab for the Prevention of COVID-19
On January 21, 2021 a press release describing the results of the BLAZE-2 study (NCT04497987) was made available. The BLAZE-2 is a US-based, multi-centre, randomized, double-blind, placebo-controlled phase III study that evaluates SARS-CoV-2 (COVID-19) neutralizing antibodies bamlanivimab (also known as LY-CoV555 or LY3819253) at 4,200 mg versus placebo for the prevention of COVID-19 in residents and staff of nursing homes and assisted living facilities. Bamlanivimab was recently approved with conditions in Canada for the treatment of mild-to-moderate COVID-19. Individuals were eligible for the BLAZE-2 study if there was at least one confirmed case of SARS-CoV-2 infection among residents or staff at the facility within 7 days of randomization. The primary study end point was the cumulative incidence of COVID-19 within 21 days. The primary end point analysis included 965 participants (299 residents and 666 staff) who tested negative for COVID-19. There was a lower frequency of symptomatic COVID-19 infection in the bamlanivimab group as compared to placebo (odds ratio 0.43, P = 0.00021) after 8 weeks of follow up. No conclusions can be drawn from this information until the full study results are published in a peer-reviewed journal.
Updated on January 26, 2021 | 15:25pm
Therapeutic Anticoagulation With Heparin and Low-Molecular-Weight Heparin
On January 22, 2021, a press release about interim results on the efficacy of full-dose anticoagulation therapy with heparin or low-molecular-weight heparin in patients hospitalized with COVID-19 was made available (NCT04372589). Heparin and low-molecular-weight heparins ( enoxaparin, tinzaparin, and dalteparin) are anticoagulants indicated, in Canada, for the treatment and prevention of thromboembolism. The Anti-Thrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC) trial is an international, open-label, adaptive, randomized controlled trial that enrolled adult patients hospitalized with COVID-19 who were not receiving organ support such as mechanical ventilation. Patients were randomized to therapeutic anticoagulation for 14 days with heparin (subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin infusion) or usual care of thromboprophylactic dose anticoagulation according to local practice. The primary outcome is days alive and free of organ support at day 21.
Although no results were reported in the press release, the press release states that interim study findings of more than 1,300 patients hospitalized with COVID-19 found that full-dose anticoagulants were superior compared to usual care thromboprophylactic dose anticoagulation. Until the full study results are published in a peer-reviewed journal, no conclusions can be drawn from this information.
Updated on January 26, 2021 | 09:50am
Colchicine
On January 23, 2021, a press release about results of the efficacy of colchicine in outpatients with COVID-19 were made available (NCT04322682). In Canada, colchicine is indicated for the treatment and prevention of gout flares. The Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA) is a randomized, double-blind, placebo-controlled, multicenter global trial that enrolled adult patients with COVID-19 who were not hospitalized and had at least one high-risk criterion. Patients were randomized to either colchicine or placebo oral tablets for 30 days (total N = 4,488). The primary outcome was a composite of death or hospitalization due to COVID-19 infection, measured up to day 30 after randomization. Compared with placebo, the risk of death or hospitalization was reduced by 21% in the overall global study population of 4,488 patients; however, this did not reach statistical significance. When the results were limited to patients with confirmed COVID-19, (N = 4,159), risk of death or hospitalization was statistically significantly reduced, although the results were not reported. For patients with confirmed COVID-19, hospitalizations were reduced by 25%, mechanical ventilation was reduced by 50%, and death was reduced by 44%. Caution should be exercised in interpreting these findings as limited information was reported in the press release. Full study results published in a peer-reviewed journal are necessary to draw any conclusions.