1 Legacy M, et al. BMJ Open 2022;12:e057024. doi:10.1136/bmjopen-2021-057024 Open access Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: study protocol for a randomised, double-blind, placebo controlled clinical trial Mark Legacy , 1,2 Dugald Seely, 1,2,3 Ellen Conte, 1,3 Athanasios Psihogios, 1,3 Tim Ramsay , 2 Dean A Fergusson , 2 Salmaan Kanji, 2,4 John-Graydon Simmons, 2 Kumanan Wilson 2 To cite: Legacy M, Seely D, Conte E, et al. Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: study protocol for a randomised, double-blind, placebo controlled clinical trial. BMJ Open 2022;12:e057024. doi:10.1136/ bmjopen-2021-057024 ► Prepublication history and additional supplemental material for this paper are available online. To view these fles, please visit the journal online (http://dx.doi.org/10.1136/ bmjopen-2021-057024). DS and KW are joint senior authors. Received 02 September 2021 Accepted 04 February 2022 For numbered affliations see end of article. Correspondence to Dr Dugald Seely; dseely@thechi.ca Protocol © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. ABSTRACT Introduction COVID-19 has caused morbidity, hospitalisations and deaths worldwide. Despite four approved vaccines for COVID-19 in Canada, there is still a need for effective treatments, especially for people in the community. Vaccine effcacy is not 100% and long- term effcacy is still unknown. Furthermore, there are challenges to herd immunity including vaccine hesitancy and underlying conditions preventing vaccination. We aim to explore if the nutrients vitamin C, vitamin D, vitamin K 2 and zinc are an effective treatment option for outpatients diagnosed with COVID-19. The primary outcome is the difference in participant-reported overall health; secondary outcomes include the effect on health status, symptom severity and duration, frequency and length of hospitalisations and mortality. Methods and analysis This study is a two-arm, parallel-group, double-blind, placebo-controlled, phase III randomised controlled trial. 200 patients will be recruited remotely from COVID-19 test centres in Ottawa, Canada associated with The Ottawa Hospital. Overall health will be measured using the EuroQol Visual Assessment Scale; health status will be measured using the EuroQol 5-dimension 5-level questionnaire; symptom severity and duration will be measured using an independently developed questionnaire; analyses will use an area under the curve approach and compare mean scores using unadjusted t tests. Study data will be recorded on electronic case report forms using the Research Electronic Data Capture platform. An independent data safety and monitoring board will perform ongoing review of the study for feasibility and safety. Ethics and dissemination This study has received ethical approval from the research ethics boards of the Canadian College of Naturopathic Medicine and the Ottawa Health Sciences Network, as well as regulatory approval from the Therapeutic Products Directorate and Natural and Non-Prescription Health Products Directorate of Health Canada. Results will be published in a peer-reviewed scientifc journal with open access. Trial registration number NCT04780061. INTRODUCTION Background and rationale COVID-19, caused by the novel SARS-CoV-2, has caused hospitalisations, morbidity and deaths worldwide. COVID-19 causes mild to moderate flu-like symptoms in most people, and can cause severe disease including pneu- monia, acute respiratory distress syndrome, multiorgan failure and death particularly in high-risk individuals. 1 As of June 2021, over 177 million people have been diagnosed with COVID-19 and over 3.8 million deaths have occurred as a result of infection. 2 There are currently four approved COVID-19 vaccines in Canada. 3 Despite this, effective treatments are still needed. None of the four vaccines are 100% effective, and long-term immunity is yet to be determined. 4 In addition, there are challenges to achieving herd immunity based on an inability for those with certain underlying conditions to be vacci- nated and vaccine hesitancy. 5 Treatments for Strengths and limitations of this study ► Blinding, randomisation and placebo control en- hance the trial’s internal validity. ► Large spectrum of outcomes allows for both rigor- ous and exploratory analyses. ► The study procedures regarding remote screening, recruitment, follow-up and product dispensation are novel in this feld and will act as a framework for future research. ► Virtual nature of the study and necessity for internet literacy may create selection bias. ► Variable length of time from symptom onset to treatment commencement due to delays in result reporting may reduce the effectiveness of the inves- tigational product. on June 25, 2023 by guest. 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