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Trial registered on ANZCTR


Registration number
ACTRN12618000217202
Ethics application status
Approved
Date submitted
29/01/2018
Date registered
9/02/2018
Date last updated
9/02/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Vitamin D dosing study in Intensive Care Unit patients
Scientific title
A Randomized Study of the effect of a Single Dose of Intramuscular Cholecalciferol on vitamin D levels in Critically Ill Adults
Secondary ID [1] 293901 0
none
Universal Trial Number (UTN)
U1111-1208-6692
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Inflammatory Response Syndrome 306380 0
vitamin D deficiency 306381 0
Condition category
Condition code
Inflammatory and Immune System 305467 305467 0 0
Other inflammatory or immune system disorders
Metabolic and Endocrine 305468 305468 0 0
Other endocrine disorders
Metabolic and Endocrine 305534 305534 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Deep intramuscular injection of cholecalciferol (Vicotrat ®)-150,000IU or 300,000IU as a single dose will be administered by a registered nurse. Blood will be sampled from existing arterial or central lines at the same time as blood is sampled as part of routine clinical management.
Intervention code [1] 300174 0
Treatment: Drugs
Comparator / control treatment
Patients receiving the dose of 150,000IU cholecalciferol
Control group
Dose comparison

Outcomes
Primary outcome [1] 304607 0
serum levels of 25-hydroxy-vitamin D,
Timepoint [1] 304607 0
day 1, 3, 7, 14 (or ICU discharge if earlier). Primary time point day 7.
Primary outcome [2] 304663 0
1,25 dihydroxy vitamin D- serum assay
Timepoint [2] 304663 0
day 1, 3, 7, 14 (or ICU discharge if earlier). Primary time point day 7.
Primary outcome [3] 304664 0
PTH- serum assay
Timepoint [3] 304664 0
day 1, 3, 7, 14 (or ICU discharge if earlier). Primary time point day 7.
Secondary outcome [1] 342529 0
serum assay of C Reactive Protein,
Timepoint [1] 342529 0
day 1, 3, 7, 14 (or at ICU discharge if earlier)
Secondary outcome [2] 342717 0
serum assay of Interleukin 6
Timepoint [2] 342717 0
day 1, 3, 7, 14 (or ICU discharge if earlier). Primary time point day 7.
Secondary outcome [3] 342718 0
serum assay of Cathelicidin
Timepoint [3] 342718 0
day 1, 3, 7, 14 (or ICU discharge if earlier). Primary time point day 7.
Secondary outcome [4] 342719 0
ionised calcium serum assay (to look for toxicity)
Timepoint [4] 342719 0
day 1, 3, 7, 14 (or ICU discharge if earlier). Primary time point day 7.

Eligibility
Key inclusion criteria
Age >16 years
Expected length of stay in ICU>48 hours
Any of 3 SIRS criteria within the last 24 hours. The SIRS criteria include –
a. Temperature <36 or >38 degrees Celsius
b. Heart rate >90 bpm
c. Respiratory rate >20/min or PaCO2<32mmHg
d. White Blood Cell count >12,000 or <4,000/mm3 or >10% bands.
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnancy
Hypercalcaemia (ionized calcium>1.3mmol/L)
Conditions associated with pathological 1 alpha-hydroxylase activity such as sarcoidosis, lymphoma and multiple myeloma.
Chronic Kidney Disease with eGFR<30ml/min
Severe coagulopathy (Platelets <30,000/cubic mm or INR>3) contraindicating intramuscular injection.
Death is likely in the next 24 hours or active treatment not deemed appropriate.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Stata 13.1 (StataCorp, College Station, TX) and Prism 6 (GraphPad Software, La Jolla, CA). Comparisons between randomized arms will be made using a chi-square or Fisher exact test for categorical covariates, and a paired t test or Wilcoxon rank-sum test for continuous covari- ates, where appropriate. Formal comparisons of change in vitamin D sufficiency from baseline will be made with McNemar test. Changes in vitamin D, laboratory parameters, and inflammatory cytokines from baseline will be compared using mixed-effects random intercept model and used available data. Pearson correlation coefficients will be used to assess the linear correlation between 25OHD and cytokines at baseline. Spearman rank correlation coefficient will be used to assess the direction and relationship of change of 25-hydroxy D and cytokines from baseline to subsequent study days. p value of less than
or equal to 0.05 will be considered statistically significant

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 9902 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 18709 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 298523 0
Charities/Societies/Foundations
Name [1] 298523 0
Intensive Care Foundation
Address [1] 298523 0
Level 2, 10 Ievers Terrace
Carlton, Victoria 3053, Australia
Country [1] 298523 0
Australia
Funding source category [2] 298531 0
Charities/Societies/Foundations
Name [2] 298531 0
St Vincents Clinic Foundation
Address [2] 298531 0
St Vincents Clinic
Victoria Street
Darlinghurst
NSW 2010
Country [2] 298531 0
Australia
Primary sponsor type
Individual
Name
Dr Priya Nair
Address
St Vincents Hospital
390 Victoria Street
Darlinghurst
NSW 2010
Country
Australia
Secondary sponsor category [1] 297671 0
Hospital
Name [1] 297671 0
St Vincents Hospital Sydney
Address [1] 297671 0
390 Victoria Street
Darlinghurst
NSW 2010
Country [1] 297671 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299501 0
St Vincents Hospital Human Research Ethics Committee
Ethics committee address [1] 299501 0
Victoria Street
Darlinghurst
NSW 2010
Ethics committee country [1] 299501 0
Australia
Date submitted for ethics approval [1] 299501 0
03/12/2012
Approval date [1] 299501 0
28/12/2012
Ethics approval number [1] 299501 0
HREC/12/SVH/322

Summary
Brief summary
Deficiency of vitamin D has been increasingly recognised as a significant public health problem, even in a sunny country like Australia. We and other groups have found that this deficiency is even more common and pronounced in critically ill patients in the Intensive Care Unit.(ICU)
There is now scientific evidence suggesting that vitamin D has widespread roles outside its traditionally recognised role in bone health. Its deficiency has been associated with cardiovascular disease, some cancers, autoimmune and inflammatory diseases, etc. We therefore propose that supplementing vitamin D in critically ill patients while they are in the ICU, particularly those showing signs of an inflammatory response, may improve their outcomes. This needs to be studied in depth within the context of a well-designed, large clinical trial.
As a variety of doses are currently used in clinical practice, the appropriate dose that is required, particularly in patients who are critically ill, is not known. The design of such trials can only be achieved by obtaining extensive background information on safety and the effects of supplementation using different doses, which are in common use, to determine which dose to use in further trials of critically ill patients and what effects can be achieved with this. Such studies are not available currently. Fortunately, vitamin D is a medication that can be used safely in a wide range of doses and we plan to use 2 doses within this range.
In this study, 50 patients admitted to the ICU who meet certain criteria, suggesting that they have signs of the inflammatory response, will be randomly allocated to receive one of 2 single doses of vitamin D by intramuscular injection. We will collect a small quantity of blood for testing at baseline and on days 1,3,7 and 14 following the dose. We will measure vitamin D and metabolite levels and markers of inflammation in order to study whether target levels can be obtained with these doses and also what effect it has on the inflammatory response. We will monitor closely for any side effects, although these would be extremely unlikely in the doses that we propose to use. We will also collect information from the patients record on routinely collected clinical data and certain outome measures. All information collected and presented will be de-identified and all records will be securely maintained to ensure privacy.
This study will provide us with vital information that we require for the next stage of this project, which is the development of a large study in a number of ICUs to explore the effects of vitamin D supplementation on outcome in this patient group. If shown to be beneficial, this could be an intervention that has a widespread global impact, including in low and middle income countries, as vitamin D is a cheap, safe and easily available medication.
Trial website
Trial related presentations / publications
Nair P, Venkatesh B, Lee P, Kerr S, Hoechter DJ, Dimeski G, Grice J, Myburgh J, Center JR.
A Randomized Study of a Single Dose of Intramuscular Cholecalciferol in Critically Ill Adults.
Crit Care Med. 2015 Nov;43(11):2313-20
Public notes
Attachments [1] 2402 2402 0 0

Contacts
Principal investigator
Name 80634 0
Dr Priya Nair
Address 80634 0
Intensive Care Unit
St Vincents Hospital
390 Victoria Street
Darlinghurst
NSW 2010
Country 80634 0
Australia
Phone 80634 0
+61 2 83823611
Fax 80634 0
Email 80634 0
Priya.Nair@svha.org.au
Contact person for public queries
Name 80635 0
Dr Priya Nair
Address 80635 0
Intensive Care Unit
St Vincents Hospital
390 Victoria Street
Darlinghurst
NSW 2010
Country 80635 0
Australia
Phone 80635 0
+61 2 83823611
Fax 80635 0
Email 80635 0
Priya.Nair@svha.org.au
Contact person for scientific queries
Name 80636 0
Dr Priya Nair
Address 80636 0
Intensive Care Unit
St Vincents Hospital
390 Victoria Street
Darlinghurst
NSW 2010
Country 80636 0
Australia
Phone 80636 0
+61 2 83823611
Fax 80636 0
Email 80636 0
Priya.Nair@svha.org.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary