The vitamin D for COVID-19 (VIVID) trial: A pragmatic cluster-randomized design

Rui Wang; Victor DeGruttola; Quanhong Lei; Kenneth H Mayer; Susan Redline; Aditi Hazra; Samia Mora; Walter C Willett; Davaasambuu Ganmaa; JoAnn E Manson

doi:10.1016/j.cct.2020.106176

The vitamin D for COVID-19 (VIVID) trial: A pragmatic cluster-randomized design

Contemp Clin Trials. 2021 Jan:100:106176. doi: 10.1016/j.cct.2020.106176. Epub 2020 Oct 10.

Authors

Affiliations

¹ Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA, USA; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA. Electronic address: rwang@hsph.harvard.edu.
² Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
³ Takeda Pharmaceutical Company, MA, USA.
⁴ Fenway Health, and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁵ Division of Sleep Medicine and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁶ Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁹ Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Abstract

Objectives: To determine the effect of vitamin D supplementation on disease progression and post-exposure prophylaxis for COVID-19 infection. We hypothesize that high-dose vitamin D3 supplementation will reduce risk of hospitalization/death among those with recently diagnosed COVID-19 infection and will reduce risk of COVID-19 infection among their close household contacts.

Methods: We report the rationale and design of a planned pragmatic, cluster randomized, double-blinded trial (N = 2700 in total nationwide), with 1500 newly diagnosed individuals with COVID-19 infection, together with up to one close household contact each (~1200 contacts), randomized to either vitamin D3 (loading dose, then 3200 IU/day) or placebo in a 1:1 ratio and a household cluster design. The study duration is 4 weeks. The primary outcome for newly diagnosed individuals is the occurrence of hospitalization and/or mortality. Key secondary outcomes include symptom severity scores among cases and changes in the infection (seroconversion) status for their close household contacts. Changes in vitamin D 25(OH)D levels will be assessed and their relation to study outcomes will be explored.

Conclusions: The proposed pragmatic trial will allow parallel testing of vitamin D3 supplementation for early treatment and post-exposure prophylaxis of COVID-19. The household cluster design provides a cost-efficient approach to testing an intervention for reducing rates of hospitalization and/or mortality in newly diagnosed cases and preventing infection among their close household contacts.

Keywords: COVID-19; Cluster randomization; Early treatment; Prophylaxis; SARS-CoV-2; Vitamin D.

Publication types

Clinical Trial Protocol
Research Support, Non-U.S. Gov't

MeSH terms

Adult
COVID-19 / mortality
COVID-19 Drug Treatment*
Comorbidity
Dietary Supplements*
Double-Blind Method
Hospitalization / statistics & numerical data
Humans
Middle Aged
Minority Groups / statistics & numerical data
Pragmatic Clinical Trials as Topic
Risk Factors
SARS-CoV-2
Seroconversion
Severity of Illness Index
Socioeconomic Factors
Vitamin D* / therapeutic use

Substances

Vitamin D