In this 16-week randomized control study, health care workers will receive a bolus dose followed by a weekly dose of vitamin D or a placebo bolus and weekly dose. This study will test whether high-dose of vitamin D supplementation decreases the incidence of laboratory-confirmed COVID19 infection (primary outcome), reduces illness severity, duration, as well as work absenteeism among health care workers (HCW) in setting at high-risk of contact with COVID-19 cases in high COVID-19 incidence areas.
Design. A 16-week triple-blind, placebo-controlled parallel-group, randomised trial of
high-dose vitamin D supplementation compared to placebo in health care workers (HCW).
Subjects: HCW caring for individuals at high-risk of infection (i.e., COVID-suspected or
confirmed cases) will be randomly allocated in a 1:1 ratio in variable block size to:
Intervention-1 oral loading dose of 100,000 IU vitamin D3 + 10000 IU weekly vitamin D3 or
Control-identical placebo loading dose + daily placebo. Follow-up: 2 (randomisation and
end-of-study) virtual or in-person visits with weekly reminders, brief health and work-status
questionnaire.
Randomisation/allocation concealment: Randomisation will be implemented using a
computer-generated random list stratified by regions; health care workers will be allocated
(1:1) using permuted block randomisation to enhance concealment.
Sample size: A total of 2414 healthcare workers will provide 80% power to detect a 20%
reduction in the risk of laboratory-confirmed COVID-19 infection. Given uncertainties in the
infection progression, a Bayesian adaptive design is used where the posterior probability of
effectiveness is the basis of inference and decision making, for study continuation or
termination.
Procedures. Use of remote or in-person randomisation and/or end-of-study visits and remote
documentation of outcomes via electronic communication, mailing of biological samples, and
external databases will facilitate enrolment, monitoring, and retention of motivated HCW in
this high-intensity trial.
Data analyses: An intention-to-treat analysis will be carried out on all randomized
participants. Efficacy and safety analyses will be performed under allocation concealment
with unblinding occurring after trial completion and analysis of primary outcomes.
Dietary Supplement: Placebo
Weekly oral dose of placebo
Dietary Supplement: Vitamin D
Weekly oral dose of Vitamin D
Other Name: cholecalciferol
Inclusion Criteria:
- are aged ≥18 and <70 years old;
- licenced to practice in Quebec;
- working or scheduled to work over the next 16 weeks in a setting at high-risk of
contact with COVID-19 infected individuals, particularly (but not only) those involved
with aerosol generating medical procedures in hospitals and/or caring for patients in
long-term care facilities;
- working in high COVID incidence areas;
- covered by the RAMQ for medical services and hospitalisations;
- has a personal email or phone (to which to send every two weeks a reminder and
questionnaire by email or text messages);
- has a fixed address (to which to send the material) in the greater Montreal or
surrounding areas.
Exclusion Criteria:
- vitamin D supplementation >400 IU/day or >12,000 IU/month in past 3 months;
- intention to take >400 IU per day during the study period;
- suspected or previously documented COVID-19 infection;
- history of nephrolithiasis, hypercalcemia, hyperphosphatemia, hyperparathyroidism,
granulomatosis disease (e.g., tuberculosis, sarcoidosis), renal impairment/failure, or
active cancer;
- use of any of the following medications: lithium, teriparatide, or digoxin;
- anticipated prolonged absence from work during the study period (i.e., pregnancy);
- enrolment in a concurrent randomized trial;
- has received a vaccine against COVID-19.
CHUM
Montreal, Quebec, Canada
CHU Sainte-Justine (CHUSJ)
Montreal, Quebec, Canada