NCT04344041

COvid-19 and Vitamin D Supplementation: a Multicenter Randomized Controlled Trial of High Dose Versus Standard Dose Vitamin D3 in High-risk COVID-19 Patients (CoVitTrial)

Completed Phase 3 Last updated 30 April 2021

What this trial tests

Phase 3 trial testing cholecalciferol 200,000 IU in Coronavirus in 260 participants. Completed in 14 January 2021.

Timeline

15 April 2020

Primary endpoint
14 January 2021

14 January 2021

Quick facts

Lead sponsor	University Hospital, Angers
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	260
Start date	15 April 2020
Primary completion	14 January 2021
Estimated completion	14 January 2021
Sites	9 locations across France

Drugs / interventions tested

• cholecalciferol 200,000 IU — full drug profile →
• cholecalciferol 50,000 IU — full drug profile →

Conditions studied

• Coronavirus — all drugs for Coronavirus →

Sponsor

University Hospital, Angers

Who can join

65 and older, any sex, with Coronavirus. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Vitamin D is a secosteroid hormone produced by the skin during Summer exposure to UVB rays. Hypovitaminosis D is common in Winter (October to March) at Northern latitudes above 20 degrees North, and from April to September at Southern latitudes beyond 20 degrees below the equator.

In the past, coronaviruses and influenza viruses have exhibited very high seasonality, with outbreaks occurring preferentially during the Winter. The Covid-19 pandemic is indeed more severe above Winter latitudes of 20 degrees, while it remains until now less severe in the Southern hemisphere, with a much lower number of deaths.

Preclinical research suggests that the SARS-Cov-2 virus enters cells via the angiotensin converting enzyme 2 (ACE2). Coronavirus viral replication downregulates ACE2, thereby dysregulating the renin-angiotensin system (RAS) and leading to a cytokine storm in the host, causing acute respiratory distress syndrome (ARDS).

Research also shows that vitamin D plays a role in balancing RAS and in reducing lung damage. On the contrary, chronic hypovitaminosis D induces pulmonary fibrosis through activation of RAS. Similarly, hypovitaminosis D has been strongly associated in the literature with ARDS, as well as with a pejorative vital prognosis in resuscitation but also in geriatric units, and with various comorbidities associated to deaths during SARS-Cov-2 infections. Conversely, vitamin D supplementation has been reported to increase immunity and to reduce inflammatory responses and the risk of acute respiratory tract infections.

High-dose oral vitamin D3 supplementation has been shown to decrease short-term mortality in resuscitation patients with severe hypovitaminosis D (17% absolute risk reduction). It is considered safe to take oral vitamin D supplementation at doses up to 10,000 IU/day for short periods, particularly in older adults, i.e. a population that is mostly affected by hypovitaminosis D and who should receive at least 1,500 IU of vitamin D daily to ensure satisfactory vitamin D status.

Vitamin D supplementation is mentioned as a potentially interesting treatment for SARS-Cov-2 infection but on a scientific basis with a low level of evidence until now.

We hypothesize that high-dose vitamin D supplementation improves the prognosis of older patients diagnosed with COVID-19 compared to a standard dose of vitamin D.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The COVID-19 pandemic and physical activity.
   Woods JA, Hutchinson NT, Powers SK, Roberts WO, et al · · 2020 · cited 287× · PMID 34189484 · DOI 10.1016/j.smhs.2020.05.006
2. Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?
   Shakoor H, Feehan J, Al Dhaheri AS, Ali HI, et al · · 2021 · cited 206× · PMID 33308613 · DOI 10.1016/j.maturitas.2020.08.003
3. An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment.
   Drożdżal S, Rosik J, Lechowicz K, Machaj F, et al · · 2021 · cited 186× · PMID 34991982 · DOI 10.1016/j.drup.2021.100794
4. Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study.
   Annweiler G, Corvaisier M, Gautier J, Dubée V, et al · · 2020 · cited 185× · PMID 33147894 · DOI 10.3390/nu12113377
5. Current status of potential therapeutic candidates for the COVID-19 crisis.
   Zhang J, Xie B, Hashimoto K. · · 2020 · cited 180× · PMID 32334062 · DOI 10.1016/j.bbi.2020.04.046
6. Perspective: Vitamin D deficiency and COVID-19 severity - plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis.
   Rhodes JM, Subramanian S, Laird E, Griffin G, et al · · 2021 · cited 152× · PMID 32613681 · DOI 10.1111/joim.13149
7. Vitamin D and survival in COVID-19 patients: A quasi-experimental study.
   Annweiler C, Hanotte B, Grandin de l'Eprevier C, Sabatier JM, et al · · 2020 · cited 149× · PMID 33065275 · DOI 10.1016/j.jsbmb.2020.105771
8. Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies.
   Market M, Angka L, Martel AB, Bastin D, et al · · 2020 · cited 115× · PMID 32655581 · DOI 10.3389/fimmu.2020.01512