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)

NCT04344041 | Completed Phase 3 DMC

• 1 other identifier: 2020-001602-34
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Coronavirus

Keywords

vitamin D; older adults

Outcome Measures

Primary Outcomes (1)

• Number of death of any cause, during the 14 days following the inclusion and intervention.

  Day 14

Secondary Outcomes (21)

• Number of death of any cause, during the 28 days following the inclusion and intervention.

  Day 28

• Clinical evolution between day 0 and day 14 based on the change of the WHO Ordinal Scale for Clinical Improvement (OSCI) for COVID-19

  Day 14

• Clinical evolution between day 0 and day 28 based on the change of the OSCI for COVID-19

  Day 28

• Rate of patients with at least one severe adverse event at day 28, according to the regulations

  Day 28

• Number of death of any cause during the 14 days following the inclusion and intervention, in patients with severe hypovitaminosis D (25-OHD <25nmol/L) at baseline

  Day 14

Study Arms (2)

Intervention group

EXPERIMENTAL

High dose of vitamin D3

Drug: cholecalciferol 200,000 IU

Comparator group

ACTIVE COMPARATOR

Standard dose of vitamin D3

Drug: cholecalciferol 50,000 IU

Interventions

cholecalciferol 200,000 IU DRUG

Patients receive a vitamin D supplementation of 400,000 IU in a single oral dose.

Intervention group

cholecalciferol 50,000 IU DRUG

Patients receive a vitamin D supplementation of 50,000 IU in a single oral dose

Comparator group

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age ≥ 65 years old
• Infection with COVID-19 diagnosed with RT-PCR SARS-CoV-2 or withCT-scan of the chest suggesting viral pneumonia of peripheral predominance in a clinically relevant context
• Patient seen in hospitalization or consultation or in nursing home
• Diagnosed within the preceding 3 days
• Having at least one of the following two risk factors for complications:
• age ≥75 years
• Peripheral capillary oxygen saturation (SpO2) ≤ 94% ambient air, or a partial oxygen pressure (PaO2) to fraction of inspired oxygen (FiO2) ratio ≤ 300 mmHg
• Patients affiliated with or benefitting from a social security scheme

You may not qualify if:

• Organ failure requiring admission to a resuscitation or high dependency unit
• Comorbidity that is life-threatening in the short-term (life expectancy \<3 months)
• Any reason that makes follow-up at day 28 impossible
• Vitamin D supplementation in the previous month, with the exception of treatment providing less than 800 IU of vitamin D per day
• Contraindication for vitamin D supplementation: active granulomatosis (sarcoidosis, tuberculosis, lymphoma), history of calcic lithiasis, known hypervitaminosis D or hypercalcemia, known intolerance to vitamin D
• Participation in another simultaneous trial
• Safeguard of justice
• Peripheral capillary oxygen saturation (SpO2) ≤92% in spite of an oxygen therapy \> 5L/min

Sponsors & Collaborators

• University Hospital, Angers: lead
• Mylan Laboratories: collaborator

Study Sites (9)

CHU Angers

Angers, France

Location

CHU Bordeaux

Bordeaux, France

Location

CH Le Mans

Le Mans, France

Location

CHU Limoges

Limoges, France

Location

CHU Nantes

Nantes, France

Location

CHU Nice

Nice, France

Location

CHU Saint Etienne

Saint-Etienne, France

Location

CH Saumur

Saumur, France

Location

CHU Tours

Tours, France

Location

Related Publications (3)

• Annweiler C, Beaudenon M, Gautier J, Gonsard J, Boucher S, Chapelet G, Darsonval A, Fougere B, Guerin O, Houvet M, Menager P, Roubaud-Baudron C, Tchalla A, Souberbielle JC, Riou J, Parot-Schinkel E, Celarier T; COVIT-TRIAL study group. High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial. PLoS Med. 2022 May 31;19(5):e1003999. doi: 10.1371/journal.pmed.1003999. eCollection 2022 May.

  PMID: 35639792 DERIVED

• Shakoor H, Feehan J, Al Dhaheri AS, Cheikh Ismail L, Ali HI, Alhebshi SH, Apostolopoulos V, Stojanovska L. Role of vitamin D supplementation in aging patients with COVID-19. Maturitas. 2021 Oct;152:63-65. doi: 10.1016/j.maturitas.2021.03.006. Epub 2021 Mar 16. No abstract available.

  PMID: 33757717 DERIVED

• Annweiler C, Beaudenon M, Gautier J, Simon R, Dubee V, Gonsard J, Parot-Schinkel E; COVIT-TRIAL study group. COvid-19 and high-dose VITamin D supplementation TRIAL in high-risk older patients (COVIT-TRIAL): study protocol for a randomized controlled trial. Trials. 2020 Dec 28;21(1):1031. doi: 10.1186/s13063-020-04928-5.

  PMID: 33371905 DERIVED

MeSH Terms

Conditions

Coronavirus Infections

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 14, 2020
• Study Start: April 15, 2020
• Primary Completion: January 14, 2021
• Study Completion: January 14, 2021
• Last Updated: April 30, 2021

Record last verified: 2021-04

Locations

FR (9)