Condition category
Nutritional, Metabolic, Endocrine
Date applied
17/09/2020
Date assigned
24/09/2020
Last edited
24/09/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Vitamin D deficiency (low vitamin D levels) is common in patients who are unwell (around 70%). This has been found to be related to an increased risk of infection and death. There are many reasons why patients are poorly and those who do survive can suffer long-term health problems in the future. It is not known whether being vitamin D deficient is a cause or effect of being unwell, and research into whether vitamin D is useful is not clear. There are no guidelines to measure and treat patients admitted to intensive care who are critically ill and are vitamin D deficient. Vitamin D is cheap and easily available, and if using vitamin D is found to help, can be quickly put into standard practice in hospitals. VITDALIZE is an international trial that aims to recruit 2400 patients from across Europe. Countries that are participating include the UK, Austria, Germany and Belgium. The UK part of VITDALIZE aims to recruit 600 patients into the trial. The aim of this trial is to see if giving a high dose of vitamin D in critically ill patients can improve survival, length of hospital stay, and quality of life.

Who can participate?
Male and females aged 18 and above admitted to ICU who are severely vitamin D deficient

What does the study involve?
Participants will be visited or contacted up to six times (days 0, 5, 12, 28, 90 and 1 year). At the beginning of the trial, participants will be given either a high dose of vitamin D or placebo (dummy supplement) on day 0 and a daily dose of either vitamin D or placebo from day 1 to day 90. On day 5 (if still in the hospital), the research team will take some more blood to see how participants are responding to treatment. On days 0, 28, 90 and after 1 year the research team will contact the participant (either in person if still in hospital or by telephone) to ask a few questions about their health. Participants will be asked to consent to provide some optional blood samples at up to three additional timepoints for future approved research. This would mean providing blood samples (25-30 ml; equivalent to 2 tablespoons) on days 0, 5 and 12.

What are the possible benefits and risks of participating?
There may be no direct benefits of taking part, but the results will lead to the best treatment being offered to patients who are unwell and vitamin D deficient.

Where is the study run from?
Birmingham Clinical Trials Unit at the University of Birmingham (UK)

When is the study starting and how long is it expected to run for?
October 2019 to October 2024

Who is funding the study?
National Institute for Health Research Health Technology Assessment Programme (NIHR HTA) (UK)

Who is the main contact?
1. Dr Dhruv Parekh
d.parekh@bham.ac.uk
2. Dr Rebekah Wale
vitdalize@trials.bham.ac.uk

Trial website

https://www.birmingham.ac.uk/vitdalize

Contact information

Type

Scientific

Primary contact

Dr Dhruv Parekh

ORCID ID

http://orcid.org/0000-0002-1508-8362

Contact details

Institute of Inflammation and Ageing
University of Birmingham
Birmingham
B15 2TT
United Kingdom
-
d.parekh@bham.ac.uk

Type

Scientific

Additional contact

Dr Rebekah Wale

ORCID ID

Contact details

Birmingham Clinical Trials Unit (BCTU)
College of Medical and Dental Sciences
Public Health Building
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 (0)121 415 8445
R.Wale@bham.ac.uk

Additional identifiers

EudraCT number

2016-002460-13

ClinicalTrials.gov number

NCT03188796

Protocol/serial number

IRAS 274476, CPMS 46276, DRKS00016940, HTA 17/147/33

Study information

Scientific title

Effect of high-dose vitamin D3 on 28-day mortality in adult critically ill patients with severe vitamin D deficiency: the UK arm of an international multi-centre, placebo-controlled, Phase III double-blind trial

Acronym

VITDALIZE UK

Study hypothesis

1. The primary hypothesis is that in critically ill patients with severe vitamin D deficiency as defined by 25(OH)D concentration ≤ 12ng/ml (30nmol/L), a high-dose vitamin D replacement strategy, compared to placebo, leads to 28-day survival.
2. Further hypotheses are that high-dose vitamin D supplementation reduces hospital and ICU mortality, 90-day and 1-year mortality, reduces the length of stay in ICU and hospital, and improves health-related quality of life of patients and is cost-effective.

Ethics approval

Approval pending, South Central – Oxford C Research Ethics Committee (oxfordc.rec@hra.nhs.uk), REC ref: 20/SC/0300

Study design

Randomized; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

The participant information sheets will be available on the VITDALIZE UK website once approved by ethics and MHRA: https://www.birmingham.ac.uk/research/bctu/trials/portfolio-v/VITDALIZE/index.aspx

Condition

Vitamin D deficiency

Intervention

Once randomised into the trial, the patient will receive either:
1. Intervention: A single loading high-dose oral/enteral vitamin D3 (540,000IU cholecalciferol, Oleovit™, Fresenius Kabi, Austria, dissolved in 37.5 ml of medium-chain triglycerides – MCT) followed by 4000 IU daily (10 drops) for 90 days.
2. Control: Placebo, identical regime of loading dose of 37.5 ml MCT (Fresenius Kabi, Austria) followed by MCT (10 drops) daily for 90 days.

Intervention type

Supplement

Phase

Drug names

Primary outcome measure

All-cause mortality, measured face-to-face (if an inpatient), by telephone, medical records, NHS digital/ONS data, at 28 days after randomisation

Secondary outcome measures

1. Mortality measured using telephone call, medical records, NHS digital/ONS data at 90 days and 1 year
2. ICU and hospital mortality measured face-to-face (if an inpatient), by telephone, medical records, NHS digital/ONS data at day 5, 28, 90 and 1 year
3. Hospital and ICU length of stay measured face-to-face (if an inpatient), by telephone, medical records, NHS digital/ONS data, starting at day 0, ending at discharge from the trial site or day 90 or mortality, whichever occurs first
4. Organ dysfunction measured by Sequential Organ Function Assessment score (SOFA), number of organ failures (0-6; defined as > 2 SOFA points in each of the 6 categories) on day 5
5. Hospital and ICU readmission measured using telephone call, medical records, NHS digital/ONS data until day 90
6. Discharge destination (home, rehabilitation, other hospital) measured using telephone, medical records, NHS digital/ONS data at discharge
7. Assessment of psychosocial functions measured using Katz Activities of Daily Life at day 90
8. Self-reported infections requiring antibiotics measured face-to-face (if an inpatient), by telephone, medical records, NHS digital/ONS data until day 90
9. Health-related quality of life measured using EQ-5D-5L at 90 days and 1 year
10. Disability assessment measured using WHODAS 2.0 at 90 days and 1 year
11. Secondary healthcare utilisation (ICU and hospital length of stay, readmissions and utilisation of hospital and community care resources after hospital discharge 1 year after randomisation), from Hospital Episode Statistics, civil registry data held by NHS Digital and patient questionnaires in the first year after randomisation
12. Health economics analysis measured face-to-face (if an inpatient), by telephone, medical records, NHS digital/ONS data at day 28, 90 and 1 year
13. Cost-effectiveness of screening for and treating VDD in critical illness measured using telephone call, medical records, NHS digital/ONS data at day 28, 90 and 1 year
14. Cost per quality-adjusted life-year gained measured using telephone call, medical records, NHS digital/ONS data at 1 year after randomisation and at end of life

Exploratory outcome:
Health-related quality of life measured using proxy EQ-5D-5L and proxy WHODAS 2.0 at randomisation (day 0)

Safety outcomes:
1. Hypercalcaemia measured using medical records on day 5
2. Self-reported falls, fractures measured face-to-face (if an inpatient), by telephone, medical records, NHS digital/ONS data until day 90
3. New episodes of kidney stones measured using medical records until day 90

Overall trial start date

01/10/2019

Overall trial end date

01/10/2024

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Patients ≥ 18 years
2. Anticipated ICU stay ≥ 48 hours
3. Admission to ICU ≤ 72 hours before screening for VDD
4. Severe VDD (25(OH)D ≤ 12 ng/ml [30 nmol/l]) using either the hospital's clinical laboratory or rapid bedside testing after ICU admission

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 2400; UK Sample Size: 600

Participant exclusion criteria

1. Severe gastrointestinal dysfunction (> 400 ml nasogastric tube residual volume)/unable to receive trial medication
2. Not expected to survive initial 48 hours of admission or treatment withdrawal imminent within 24 hours
3. Patient with DNAR (Do Not Attempt Resuscitation) orders in place
4. Hypercalcemia (> 2.65 mmol/l corrected calcium and/or > 1.35 mmol/l ionized calcium at screening)
5. Known kidney stones within the last 12 months
6. Known active tuberculosis within the last 12 months
7. Known sarcoidosis within the last 12 months
8. Women of childbearing age who have tested positive for pregnancy or who are lactating
9. Known hypersensitivity to the trial drug or excipient
10. Medical team deem it not suitable to include patient
11. Known prisoners in the custody of HM Prison and Probation services

Recruitment start date

01/10/2020

Recruitment end date

01/10/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University Hospitals Birmingham NHS Foundation Trust
Trust HQ, PO Box 9551 Queen Elizabeth Medical Centre Edgbaston
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Cardiff & Vale University LHB
Corporate Headquarters Heath Park
Cardiff
CF14 4XW
United Kingdom

Trial participating centre

Bradford Teaching Hospitals NHS Foundation Trust
Bradford Royal Infirmary Duckworth Lane
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

South Tees Hospitals NHS Foundation Trust
James Cook University Hospital Marton Road Middlesbrough
Cleveland
TS4 3BW
United Kingdom

Trial participating centre

University Hospitals Coventry and Warwickshire NHS Trust
Walsgrave General Hospital Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Trial participating centre

Bolton NHS Foundation Trust
The Royal Bolton Hospital Minerva Road Farnworth
Bolton
BL4 0JR
United Kingdom

Trial participating centre

Guy's and St Thomas' NHS Foundation Trust
St Thomas' Hospital Westminster Bridge Road
London
SE1 7EH
United Kingdom

Trial participating centre

Walsall Healthcare NHS Trust
Manor Hospital Moat Road
Walsall
WS2 9PS
United Kingdom

Trial participating centre

County Durham and Darlington NHS Foundation Trust
Darlington Memorial Hospital Hollyhurst Road
Darlington
DL3 6HX
United Kingdom

Trial participating centre

The Dudley Group NHS Foundation Trust
Russells Hall Hospital Pensnett Road
Dudley
DY1 2HQ
United Kingdom

Trial participating centre

North Bristol NHS Trust
Southmead Hospital Southmead Road Westbury-On-Trym
Bristol
BS10 5NB
United Kingdom

Trial participating centre

Taunton and Somerset NHS Foundation Trust
Musgrove Park Hospital
Taunton
TA1 5DA
United Kingdom

Trial participating centre

Belfast Health & Social Care Trust
Knockbracken Healthcare Park Saintfield Road
Belfast
BT8 8BH
United Kingdom

Trial participating centre

Portsmouth Hospitals NHS Trust
Queen Alexandra Hospital Southwick Hill Road Cosham
Portsmouth
PO6 3 LY
United Kingdom

Trial participating centre

Mid Yorkshire Hospitals NHS Trust
Pinderfields Hospital Aberford Road
Wakefield
WF1 4DG
United Kingdom

Trial participating centre

East Lancashire Hospitals NHS Trust
Royal Blackburn Hospital Haslingden Road
Blackburn
BB2 3HH
United Kingdom

Trial participating centre

Great Western Hospitals NHS Foundation Trust
Great Western Hospital Marlborough Road
Swindon
SN3 6BB
United Kingdom

Sponsor information

Organisation

Medical University of Graz

Sponsor details

Auenbruggerplatz 2
Graz
8036
Austria
+43 (0)31638582383
karin.amrein@medunigraz.at

Sponsor type

University/education

Website

http://www.medunigraz.at/en/

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme; Grant Codes: 17/147/33

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

1. The international protocol has been published: https://pubmed.ncbi.nlm.nih.gov/31722941/
2. The UK protocol has some minor changes, this will be made available on the VITDALIZE UK website once approved by ethics and MHRA: https://www.birmingham.ac.uk/research/bctu/trials/portfolio-v/VITDALIZE/index.aspx
3. Planned publication will be in a high-impact peer-reviewed journal approximately 1 year after the overall trial end date

IPD sharing statement
The datasets generated and/or analysed during the current study will be included in the subsequent results publication.

Intention to publish date

01/10/2025

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

17/09/2020: Trial's existence confirmed by the NIHR.