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Treatments

The British Columbia COVID-19 Therapeutics Committee provides guidance on the most current research on the use of therapies in the management of COVID-19.

Clinical guidance

Clinical Reference Group Recommendations: Therapies for COVID-19

UPDATED: April 9, 2021 - update pending

The British Columbia COVID-19 Therapeutics Committee (CTC) meets regularly to discuss the most current research on the use of therapies in the management of COVID-19.

Evidence for the role of various therapies for the prevention or treatment of COVID-19 is quickly emerging and represents a rapidly evolving area of research.

While positive results for a small number of treatments are being published, the efficacy, safety and role in therapy for most pharmacological treatments for COVID-19 remain unknown. Currently, international bodies such as the World Health Organization (WHO), recommend that unproven pharmacological therapies for COVID-19 not be used outside of clinical trials. Within British Columbia, the use of unproven COVID-19 drug therapies outside of clinical trials is NOT recommended. Participation in clinical trials allows for ethical evaluation of the efficacy and safety of potential agents, minimizes inconsistencies in usage that is harmful to the clinical community and the public, and protects the drug supply chain.  It is recognized that there may be extenuating individual circumstances where clinicians decide to use such therapies when clinical trials are unavailable. In settings where unproven therapies are used, the WHO has provided a standardized case report form for data collection to ensure that there is contribution to scientific research and the clinical community.

In circumstances where practice-changing results become available, such data should carefully be interpreted with particular attention to effect size, applicability, safety and practical issues of incorporating the evidence into practice that are specific to patients in British Columbia. The recommendations listed below have been written with careful consideration of these points.

These recommendations apply to hospitalized and non-hospitalized adult patients with confirmed or suspected COVID-19. Find recommendations for Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19.     

Recommendations for Specific Therapies:
  1. Corticosteroids (hospitalized patients requiring oxygen or higher levels of respiratory support)
    Dexamethasone 6 mg IV/PO q24h for up to 10 days is strongly recommended (RECOVERY trial), unless higher doses are clinically indicated (e.g., asthma exacerbation, refractory septic shock, history of chronic steroid use, obstetric use for fetal lung maturation).

    Hydrocortisone 50 mg IV q6h is recommended as an alternative (REMAP-CAP trial). If dexamethasone and hydrocortisone are not available, methylprednisolone 32 mg IV q24h or prednisone 40 mg PO daily are recommended.

  2. Tocilizumab
    Tocilizumab 400 mg IV (single dose) OR Sarilumab 400mg IV (single dose) is recommended (REMAP-CAP, RECOVERY) for patients requiring life support due to confirmed COVID-19.  This includes high-flow oxygen support (e.g., Optiflow) if flow rate > 30 L/min and FiO2 > 0.4 OR invasive or non-invasive ventilation OR vasopressor or inotropic support.  Tocilizumab or sarilumab must be administered within 24 hours of the initiation of life support measures. Patients admitted to hospital for more than 14 days with symptoms of COVID-19 should not receive tocilizumab or sarilumab for this indication. Tocilizumab or sarilumab should only be initiated when life support is required because of COVID-19 rather than other causes (such as bacterial infection, pulmonary embolism, etc).

    Tocilizumab is not recommended for patients receiving low-flow oxygen support. The RECOVERY trial found a survival benefit of 4% (tocilizumab 29% vs. usual care 33% 28-day mortality) in patients who had CRP >75 mg/L AND low-flow oxygen, non-invasive respiratory support, or invasive mechanical ventilation. However, considering the scarcity of IL-6 blockers in Canada, drug therapy should be prioritized to the persons with both the highest need and the greatest likelihood of benefiting from the therapy. Combined with outstanding issues in the preliminary findings of the RECOVERY trial (e.g. 17% of patients randomized to tocilizumab not receiving the drug), the CTC recommends prioritizing tocilizumab use only for critically ill patients at this time, which is the population shown to benefit in both the REMAP and RECOVERY trials.

  3. Remdesivir
    Remdesivir has not demonstrated benefit in survival, progression to ventilation or length of hospital stay and remains uncertain with respect to shortening time to recovery by 5 days. The World Health Organization (WHO) has issued a conditional recommendation against the use of remdesivir in hospitalized COVID-19 patients. Further evaluation in approved clinical trials is strongly encouraged. If remdesivir is used outside of clinical trials, full disclosure of risks and benefits with consideration of patient values and preferences are necessary, as it is not considered standard of care. Furthermore, it should be restricted to hospitalized patients requiring supplemental oxygen but not requiring non-invasive or invasive mechanical ventilation.

  4. Lopinavir / Ritonavir (Kaletra®)
    Lopinavir/ritonavir is not recommended for treatment of COVID-19.  Lopinavir/ritonavir is not recommended for prophylaxis of COVID-19 outside of approved randomized-controlled trials.

  5. Chloroquine or Hydroxychloroquine
    Chloroquine or hydroxychloroquine (with or without azithromycin) is not recommended for treatment or prophylaxis of COVID-19.

  6. Oseltamivir
    Oseltamivir is not recommended for treatment or prophylaxis of COVID-19.

  7. Ribavirin and Interferon
    Interferon IV/SC is not recommended for the treatment of COVID-19.  Ribavirin/Interferon (Inhaled) is not recommended outside of approved clinical trials.

  8. Colchicine 
    The CTC does not recommend the routine use of colchicine at this time. In patients aged 40 years or older with PCR-confirmed COVID-19 who have at least one risk factor and no contraindications††, colchicine 0.6 mg PO BID x 3 days, then 0.6 mg daily x 27 days may be considered on a case-by-case basis in discussion with the patient by clearly highlighting the uncertainty in the benefit of treatment, and the risks and potential adverse effects. Informed consent should be obtained and treatment initiated as soon as possible.

  9. Ivermectin
    Ivermectin is not recommended for treatment or prophylaxis of COVID-19 outside of approved randomized-controlled trials.  
       
  10. Ascorbic Acid and Vitamin D
    Ascorbic acid and Vitamin D are not recommended for treatment or prophylaxis of COVID-19 outside of approved randomized-controlled trials.

  11. Biologics/Small Molecules (Anakinra, Baricitinib, Ruxolitinib)
    Biologics/Small Molecules (Anakinra, Baricitinib, Ruxolitinib) are not recommended for treatment or prophylaxis of COVID-19 outside of approved randomized-controlled trials.

  12. Passive Immunotherapies (Convalescent Plasma#/IVIG)
    Convalescent Plasma#/IVIG is not recommended for treatment or prophylaxis of COVID-19 outside of approved randomized-controlled trials.

  13. Monoclonal Antibodies/Antibody Cocktails
    Monoclonal Antibodies/Antibody Cocktails (e.g. bamlanivimab) are not recommended for treatment or prophylaxis of COVID-19 outside of approved randomized-controlled trials.

  14. Antibiotics
    Antibiotics should be initiated based on local institutional antibiograms and sensitivities if bacterial infection is suspected.

  15. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
    Acetaminophen is recommended preferentially for symptomatic management of COVID-19 but do not recommend against the use of NSAIDs such as ibuprofen. 

  16. Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs)
    Patients on ACE inhibitors and ARBs are recommended to continue these agents as indicated and not cease therapy solely on the basis of COVID-19.

  17. Venous Thromboembolism (VTE) prophylaxis
    Enoxaparin 30 mg SC bid is suggested as the preferred dose for VTE prophylaxis in critically ill patients with COVID-19. Enoxaparin 30 mg SC bid should be considered for VTE prophylaxis in hospitalized ward-based patients with COVID-19. This dose was selected to reduce incident VTE and potentially save health care resources with patient transport and minimize risk of COVID-19 transmission to staff and others. Suggest even higher doses of enoxaparin for hospitalized patients with weight above 100 kg or BMI above 40 kg/m2.

  18. SSRIs
    SSRIs are not recommended for treatment or prophylaxis of COVID-19 outside of approved randomized-controlled trials.
            
  19. Other investigational therapies
    Other investigational agents including arbidol, ASC09, azvudine, baloxavir marboxil/favipiravir, camostat mesylate, darunavir/cobicistat, camrelizumab, famotidine, niacin, thymosin, natural health products, and traditional Chinese medicines are not recommended for treatment or prophylaxis of COVID-19 due to lack of data, lack of availability, or both.

# Denotes that a clinical trial of named therapy is currently planned or underway in British Columbia.

Links to listing of registered trial in British Columbia and Canada:
*Recommendations are consistent with guidelines from the World Health Organization (WHO), the Surviving Sepsis Campaign (SSC) (a joint initiative of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)), the Public Health Agency of Canada (PHAC), the Canadian Critical Care Society (CCCS), the Association of Medical Microbiology and Infectious Diseases Canada (AMMI), and The Australian and New Zealand Intensive Care Society (ANZICS).

Age >70 years, obesity (BMI >30 kg/m2), diabetes, hypertension (systolic >150 mmHg), respiratory or coronary disease, heart failure, fever >38.4°C, and dyspnea.

††Contraindications – GFR <30 mL/min, inflammatory bowel disease, chronic diarrhea or malabsorption, neuromuscular disease, severe liver disease, chemotherapy, current colchicine treatment, hypersensitivity to colchicine, or concurrent medications that interact with colchicine (e.g. amiodarone, azoles, carvedilol, cyclosporine, estradiol, macrolides, propafenone, protease inhibitors, quinidine, quinine, verapamil).

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