Ad-hoc COVID-19 Clinical Pharmacology Task Group: Statement on hydroxychloroquine

Clinical Pharmacology Task Group (CPTG) meeting date: June 12, 2020

On this page

• Policy question
• Recommendations
• Background
• Considerations
  • Post-hoc statement
• Acknowledgements

Policy question

The Public Health Agency of Canada (PHAC) asked the ad-hoc COVID-19 Clinical Pharmacology Task Group (CPTG) for advice on whether known and potential benefits of hydroxychloroquine outweigh known and potential risks in the treatment or prevention of COVID-19.

Recommendations

The ad-hoc Clinical Pharmacology Task Group recommends against the use of hydroxychloroquine as a treatment for patients with COVID-19 due to negligible evidence of efficacy and significant potential for harm leading to a high risk-to-benefit ratio. This guidance is not meant to replace clinical judgement or specialist consultation.

This guidance will be updated as additional peer-reviewed evidence emerges as warranted by the Clinical Pharmacology Task Group members.

This statement was approved by the Clinical Pharmacology Task Group on June 19, 2020.

Background

As of June 10, 2020, 215 clinical trials were registered worldwide to investigate hydroxychloroquine (HCQ) as a treatment or chemoprophylaxis for COVID-19, with 10 trials in Canada^{Footnote 1}.  A series of developments have brought into question the benefit-risk of HCQ:

• On June 11, 2020, the UK-based RECOVERY trial, a large randomized controlled trial testing different investigational COVID-19 therapies in hospitalized patients, halted its HCQ treatment arm after discerning no evidence of clinical benefit (n=1,542 patients receiving HCQ, n=3,132 patients receiving standard of care)^{Footnote 2}. The results of the RECOVERY trial have not yet been published in a peer-reviewed journal.
• On June 12, 2020, the ad-hoc COVID-19 Clinical Pharmacology Task Group met, and part of the discussions included a benefit-risk profile of HCQ to be included in the pandemic response.  The Task Group discussed recent global changes in evidence and clinical practice, but were not provided with a complete evidence summary.
• Post-hoc statement:
  • On June 15, 2020, the FDA revoked the emergency use authorization for chloroquine and HCQ as a treatment for certain hospitalized patients with COVID-19 when a clinical trial was not available or participation in one was not feasible, as a result of analysis of the totality of scientific evidence suggesting a lack of clinical benefit^{Footnote 3}. Similarly, France has revoked its decree for off-label use of HCQ to treat COVID-19^{Footnote 4}.
  • On June 17, 2020, the WHO announced that they will no longer randomize patients into the HCQ arm of the large multi-national SOLIDARITY trial, which evaluates the drug in hospitalized patients with COVID-19^{Footnote 5}.
• However, several ongoing trials have not yet reported results. The trials mentioned above are in later stages of disease and in hospitalized (i.e., more severely ill) patients. Ongoing trials are evaluating the use of the drug in earlier and milder stages of the disease, which, based on the mechanism of action of most antiviral drugs, is where it would most likely have benefit, if any.

Considerations

• In addition to its approved use for the prevention and treatment of malaria, lupus, and rheumatoid arthritis, HCQ has a history of experimental use to treat other emerging infectious diseases with little reported efficacy.
• To date, there is marginal and conflicting evidence of the efficacy of HCQ as a treatment or chemoprophylaxis for COVID-19. However, it is unknown whether evidence of efficacy will emerge from ongoing studies in different subpopulations of patients with COVID-19, or whether currently registered trials will continue to include their HCQ treatment arm.
• Use of hydroxychloroquine in COVID-19 patients has been associated with serious safety signals, mostly notably life-threatening arrhythmias.
• The Clinical Pharmacology Task Group noted a high risk-to-benefit ratio for hydroxychloroquine as a treatment for COVID-19, based on limited early data in hospitalized patients.

Post-hoc statement

• The hydroxychloroquine treatment arm in the UK-based RECOVERY trial referenced in the above statement has since been published^{Footnote 6}.

Acknowledgments

This statement was prepared by:  N Forbes, M Patel, M Rieder, and M Salvadori, on behalf of the Clinical Pharmacology Task Group (CPTG).

CPTG Members:  M Salvadori (Co-Chair), M Rieder (Co-chair), M Lordkipanidze, R Hall, M Piquette-Miller, A Collier and S Murthy.

CPTG gratefully acknowledges the contribution of:  N Abraham, A House, M Tunis, A Killikelly, Y Chung, J Courtemanche, A Coady, B Mitchelmore, E Chong, and R Goddard.

CPTG also gratefully acknowledges the contribution from the Canadian Agency for Drugs and Technologies in Health.