VITDALIZE UK: Effect of high-dose vitamin D3 on 28-day mortality in adult critically ill patients with severe vitamin D deficiency
| ISRCTN | ISRCTN44822292 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN44822292 |
| ClinicalTrials.gov (NCT) | NCT03188796 |
| Clinical Trials Information System (CTIS) | 2016-002460-13 |
| Integrated Research Application System (IRAS) | 274476 |
| Central Portfolio Management System (CPMS) | 46276 |
| Grant Code | DRKS00016940, HTA 17/147/33 |
| Sponsor | Medical University of Graz |
| Funder | Health Technology Assessment Programme; Grant Codes: 17/147/33 |
- Submission date
- 17/09/2020
- Registration date
- 24/09/2020
- Last edited
- 17/11/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
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?
Males and females aged 18 years 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 July 2027
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. Serena Dhir
s.dhir@bham.ac.uk
Contact information
Scientific
Institute of Inflammation and Ageing
University of Birmingham
Birmingham
B15 2TT
United Kingdom
 ORCID ID |
0000-0002-1508-8362 |
|---|---|
| d.parekh@bham.ac.uk |
Scientific
Birmingham Clinical Trials Unit
Public Health Building (Y17)
University of Birmingham
Birmingham
B15 2TT
United Kingdom
| Phone | +44 (0) 121 415 8445 |
|---|---|
| vitdalize@trials.bham.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomized; Interventional; Design type: Treatment, Drug |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| 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 |
| Study acronym | VITDALIZE UK |
| Study objectives | 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(s) | Approved 03/11/2020, South Central – Oxford C Research Ethics Committee (Level 3, Block B, Whitefriars, Lewins Mead, Bristol, BS1 2NT, UK; +44 (0)207 104 8041; oxfordc.rec@hra.nhs.uk), REC ref: 20/SC/0300 |
| Health condition(s) or problem(s) studied | 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 |
| Primary outcome measure(s) |
All-cause mortality, measured face-to-face (if an inpatient), by telephone, medical records, NHS digital/ONS data, at 28 days after randomisation |
| Key secondary outcome measure(s) |
1. Mortality measured using telephone call, medical records, NHS digital/ONS data at 90 days and 1 year |
| Completion date | 31/07/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 100 Years |
| Sex | All |
| Target sample size at registration | 2400 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 12/04/2021 |
| Date of final enrolment | 31/07/2026 |
Locations
Countries of recruitment
- United Kingdom
- England
- Northern Ireland
- Wales
Study participating centres
Queen Elizabeth Medical Centre
Edgbaston
Birmingham
B15 2TH
England
Marton Road
Middlesbrough
Cleveland
TS4 3BW
England
Minerva Road
Farnworth
Bolton
BL4 0JR
England
Westminster Bridge Road
London
SE1 7EH
England
Saintfield Road
Belfast
BT8 8BH
Northern Ireland
Aberford Road
Wakefield
WF1 4DG
England
Haslingden Road
Blackburn
BB2 3HH
England
Marlborough Road
Swindon
SN3 6BB
England
Grimsby
DN33 2BA
England
Derriford
Plymouth
PL6 8DH
England
Castle Lane East
Bournemouth
BH7 7DW
England
Dudley Road
Birmingham
B18 7QH
England
Taunton
TA1 5DA
England
Scunthorpe
DN15 7BH
England
Oldham
OL1 2JH
England
Derby Road
Nottingham
NG7 2UH
England
Prescot Street
Liverpool
L7 8XP
England
Barnsley
S75 2EP
England
Aldermaston Road
Basingstoke
RG24 9NA
England
London
SE5 8AB
England
Kingston upon Thames
KT2 7QB
England
Beckett Street
Leeds
LS9 7TF
England
Northampton
NN1 5BD
England
Pensnett Road
Dudley
DY1 2HQ
England
Warrington Road
Prescot
L35 5DR
England
Turner Road
Colchester
CO4 5JL
England
Magdala Avenue
London
N19 5NF
England
Ethelbert Road
Canterbury
CT1 3NG
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request (Updated 20/11/2020, previously: The datasets generated and/or analysed during the current study will be included in the subsequent results publication) |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 12/11/2019 | 15/01/2025 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
17/11/2025: The following changes were made to the study record:
1. The date of final enrolment was changed from 31/01/2026 to 31/07/2026.
2. The completion date was changed from 31/01/2026 to 31/07/2027.
3. The study participating centres were updated.
18/03/2025: The following changes were made:
1. Colchester General Hospital was replaced with East Suffolk and North Essex NHS Foundation Trust as a study participating centre.
2. The recruitment end date was changed from 31/03/2025 to 31/01/2026.
17/03/2025: Barnsley Hospital NHS Foundation Trust, Hampshire Hospitals NHS Foundation Trust, Colchester General Hospital, Kings College Hospital, Kingston Hospital, Leeds Teaching Hospitals NHS Trust, Northampton General Hospital NHS Trust, The Dudley Group NHS Foundation Trust and Mersey and West Lancashire Teaching Hospitals NHS Trust were added as study participating centres.
16/01/2025: The overall end date was changed from 01/10/2025 to 31/01/2026.
15/01/2025: The recruitment end date was changed from 01/11/2023 to 31/03/2025. Cardiff & Vale University LHB, Bradford Teaching Hospitals NHS Foundation Trust, and University Hospitals Coventry and Warwickshire NHS Trust were removed from the study participating centres. Contact details updated.
12/12/2022: Contact details updated.
11/10/2022: The following changes have been made:
1. The recruitment end date has been changed from 01/10/2022 to 01/11/2023.
2. The overall trial end date has been changed from 01/10/2024 to 01/10/2025 and the plain English summary updated accordingly.
3. Walsall Healthcare NHS Trust, County Durham and Darlington NHS Foundation Trust, The Dudley Group NHS Foundation Trust, North Bristol NHS Trust, Taunton and Somerset NHS Foundation Trust and Portsmouth Hospitals NHS Trust have been removed from the trial participating centres and Diana, Princess of Wales Hospital, Derriford Hospital, Royal Bournemouth Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Musgrove Park Hospital, Scunthorpe General Hospital, The Royal Oldham Hospital, Nottingham University Hospitals NHS Trust - Queen's Medical Centre Campus and Royal Liverpool University Hospital NHS Trust added.
4. The intention to publish date has been changed from 01/10/2025 to 01/10/2026.
23/04/2020: The recruitment start date was changed from 01/01/2021 to 12/04/2021.
20/11/2020: The following changes were made to the trial record:
1. The ethics approval was added.
2. The recruitment start date was changed from 01/10/2020 to 01/01/2021.
3. The publication and dissemination plan was updated.
4. The participant level data was changed from 'Other' to 'Available of request'.
17/09/2020: Trial's existence confirmed by the NIHR.
