PRevention of COVID-19 With Oral Vitamin D Supplemental Therapy in Essential healthCare Teams (PROTECT)

PROTECT RCT (PRevention of COVID-19 With Oral Vitamin D Supplemental Therapy in Essential healthCare Teams

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Vitamin D

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1T8
      • CHUM
    • Montreal, Quebec, Canada, H3T1C5
      • CHU Sainte-Justine (CHUSJ)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 10 placebo tablets taken orally at baseline, followed by 1 placebo tablet once a week for 16 weeks Note that the study may be prolonged according to the overall infection rate monitored monthly.	Dietary supplement: Placebo; Weekly oral dose of placebo
Experimental: Vitamin D3; 10 tablets containing 10,000 IU (total : 100,000 IU) of Vitamin D3 taken orally at baseline, followed by 10,000 IU once a week for 16 weeks. Note that the study may be prolonged according to the overall infection rate monitored monthly.	Dietary supplement: Vitamin D; Weekly oral dose of Vitamin D; Other Names: cholecalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in incidence of laboratory-confirmed COVID-19 infection	documented by salivary or NP samples obtained clinically for screening or diagnostic purposes throughout the study period, self-obtained salivary samples at endpoint, analysed by RT-qPCR or COVID-19 seroconversion at endpoints	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of disease severity	5-category ordinal variable [asymptomatic, mild (managed at home); moderate (hospitalisation without supplemental oxygen; severe (oxygen supplementation); critical (mechanical ventilation/death)	up to 16 weeks
Duration of symptoms in COVID-19 positive participants	For asymptomatic positive COVID-19 participants, symptoms will be recorded in a daily diary up to 14 days. Symptomatic positive COVID-19 participants will record their symptoms in a daily diary up to 48 hours after the resolution of symptoms	up to 16 weeks
Number of participants with COVID-19 positive IgG serology	SARS-CoV-2 IgG Diasorin on Liaison XL platform	16 weeks
Number of workday absences due to COVID-19 suspected/confirmed infection	Participant-reported; reported by Direction of Human Resource (or for physicians, Direction des services professionnelles) databases	16 weeks
Number of workday absences for any reason	Participant-reported; reported by Direction of Human Resource (or for physicians, Direction des services professionnelles) databases	16 weeks
Adverse health events	Number and distribution of adverse health events	16 weeks

Collaborators and Investigators

• Sponsor: St. Justine's Hospital
• Collaborators: Canadian Institutes of Health Research (CIHR); Laboratoire RIVA
• Investigators: Principal Investigator: Francine M Ducharme, MD, St. Justine's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2021
• Primary Completion (Actual): May 4, 2021
• Study Completion (Actual): May 25, 2021

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: July 21, 2020
• First Posted (Actual): July 23, 2020

Study Record Updates

• Last Update Posted (Actual): May 28, 2021
• Last Update Submitted That Met QC Criteria: May 26, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Vitamin D; Primary prevention; Health care workers
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: MP-21-2021-3044

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No