Clinical trial NCT04483635: PRevention of COVID-19 With Oral Vitamin D Supplemental Therapy in Essential healthCare Teams
Official title: PROTECT RCT (PRevention of COVID-19 With Oral Vitamin D Supplemental Therapy in Essential healthCare Teams
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: COVID-19
Keywords: Vitamin D
Primary prevention
Health care workers
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Laboratoire RIVA
First posted: 2020-07-23
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel-group, placebo controlled trial of vitamin D3 supplementation
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in incidence of laboratory-confirmed COVID-19 infection
timeFrame: 16 weeks
Secondary outcomes:
measure: Distribution of disease severity
timeFrame: up to 16 weeks
measure: Duration of symptoms in COVID-19 positive participants
timeFrame: up to 16 weeks
measure: Number of participants with COVID-19 positive IgG serology
timeFrame: 16 weeks
measure: Number of workday absences due to COVID-19 suspected/confirmed infection
timeFrame: 16 weeks
measure: Number of workday absences for any reason
timeFrame: 16 weeks
measure: Adverse health events
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: CHUM
state: Quebec
city: Montreal
country: Canada
facility: CHU Sainte-Justine (CHUSJ)
state: Quebec
Study officials:
affiliation: St. Justine's Hospital
name: Francine M Ducharme, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHUM
name: Cecile Tremblay, MD
role: PRINCIPAL_INVESTIGATOR
References: