NCT02868827

Brief Summary

The purpose of the research study is to determine whether a single high dose of vitamin D is helpful in reducing critical illness related complications in intensive care patients who are having sever vitamin D deficiency. Vitamin D deficiency is quite common in critically ill patients ranging from 81.5% to 99%. A number of scientific studies have documented a strong correlation between low levels of vit.D and increased rate of adverse outcomes including infection, acute kidney injury and mortality in ICU patients. A recent randomized controlled trial (RCT) has demonstrated a 50% reduction in hospital mortality in severe vit.D deficient patients following a single high dose of cholecalciferol (Vitamin D3). However, the role of Vit.D supplementation to boost up host immune system and eventually reduction of mortality has yet to be determined by large randomized controlled trials in humans. Hence the study aims to run a randomized controlled trial (RCT) in order to study the role of Vitamin D in critically ill patients.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
127

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Aug 2017

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 7, 2016

Completed
9 days until next milestone

First Posted

Study publicly available on registry

August 16, 2016

Completed
1 year until next milestone

Study Start

First participant enrolled

August 27, 2017

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 9, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 9, 2019

Completed
Last Updated

June 18, 2020

Status Verified

June 1, 2020

Enrollment Period

2.2 years

First QC Date

August 7, 2016

Last Update Submit

June 16, 2020

Conditions

Vitamin D DeficiencyCritical Illness

Keywords

cholecalciferol and critical illnessMortality and cholecalciferol supplementation

Outcome Measures

Primary Outcomes (1)

  • Reduction in hospital mortality

    as assessed by hospital mortality rate

    28 days

Secondary Outcomes (9)

  • Emergence of Multidrug resistant (MDR) organisms

    28 days

  • Vasopressor requirement

    28 days

  • Ventilator free days

    28 days

  • ICU length of stay

    28 days

  • Hospital length of stay

    28 days

  • +4 more secondary outcomes

Study Arms (2)

Cholecalciferol

EXPERIMENTAL

This group of patients will receive single high dose of vitamin D (Cholecalciferol) dissolved in 45 ml of fresh milk (Nestle)

Drug: Cholecalciferol

Placebo

PLACEBO COMPARATOR

This group of patients will receive placebo - 45 ml of fresh milk (Nestle) so that the amount, color, smell, taste etc will be the same as that of experimental drug)

Other: Milk (Nestle)

Interventions

CholecalciferolDRUG

400000 international Units of cholecalciferol will be dissolved in 45 ml of fresh milk (Nestle) and it will be given to interventional group patients through enteral route within 24 hours of ICU admission as a single dose.

Also known as: Vitamin D3
Cholecalciferol
Milk (Nestle)OTHER

45 ml of Nestle milk will given to patients assigned as placebo

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • years or older.
  • Both male and female
  • Within 24 hours from admission.
  • Having 25 -Hydroxyvitamin D level of 12 ng/ml or lower.

You may not qualify if:

  • Pregnant or lactating females.
  • Do not resuscitate (DNR) status or comfort measures only
  • No consent
  • Severely impaired gastrointestinal functions (e.g, paralytic ileus, continuous nasogastric tube drainage, strict nil per oral- no medication, malabsorption syndrome, chronic diarrhea etc)
  • History of renal stones within past year
  • Past history of hypercalcemia, tuberculosis or sarcoidosis.
  • Baseline serum total calcium ≥10.6 mg/dl or ionized serum calcium ≥ 5.4 mg/dl.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

King Abdullah Medical City, Holy Capital

Mecca, Makkah Western, 21955, Saudi Arabia

Location

Related Publications (21)

  • Perron RM, Lee P. Efficacy of high-dose vitamin D supplementation in the critically ill patients. Inflamm Allergy Drug Targets. 2013 Aug;12(4):273-81. doi: 10.2174/18715281113129990047.

    PMID: 23782210BACKGROUND

  • Quraishi SA, De Pascale G, Needleman JS, Nakazawa H, Kaneki M, Bajwa EK, Camargo CA Jr, Bhan I. Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis: A Randomized, Placebo-Controlled Trial. Crit Care Med. 2015 Sep;43(9):1928-37. doi: 10.1097/CCM.0000000000001148.

    PMID: 26086941BACKGROUND

  • Higgins DM, Wischmeyer PE, Queensland KM, Sillau SH, Sufit AJ, Heyland DK. Relationship of vitamin D deficiency to clinical outcomes in critically ill patients. JPEN J Parenter Enteral Nutr. 2012 Nov;36(6):713-20. doi: 10.1177/0148607112444449. Epub 2012 Apr 20.

    PMID: 22523178BACKGROUND

  • Lee P, Eisman JA, Center JR. Vitamin D deficiency in critically ill patients. N Engl J Med. 2009 Apr 30;360(18):1912-4. doi: 10.1056/NEJMc0809996. No abstract available.

    PMID: 19403914BACKGROUND

  • Matthews LR, Ahmed Y, Wilson KL, Griggs DD, Danner OK. Worsening severity of vitamin D deficiency is associated with increased length of stay, surgical intensive care unit cost, and mortality rate in surgical intensive care unit patients. Am J Surg. 2012 Jul;204(1):37-43. doi: 10.1016/j.amjsurg.2011.07.021. Epub 2012 Feb 10.

    PMID: 22325335BACKGROUND

  • Braun A, Chang D, Mahadevappa K, Gibbons FK, Liu Y, Giovannucci E, Christopher KB. Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill. Crit Care Med. 2011 Apr;39(4):671-7. doi: 10.1097/CCM.0b013e318206ccdf.

    PMID: 21242800BACKGROUND

  • Braun AB, Litonjua AA, Moromizato T, Gibbons FK, Giovannucci E, Christopher KB. Association of low serum 25-hydroxyvitamin D levels and acute kidney injury in the critically ill. Crit Care Med. 2012 Dec;40(12):3170-9. doi: 10.1097/CCM.0b013e318260c928.

    PMID: 22975885BACKGROUND

  • Arnson Y, Gringauz I, Itzhaky D, Amital H. Vitamin D deficiency is associated with poor outcomes and increased mortality in severely ill patients. QJM. 2012 Jul;105(7):633-9. doi: 10.1093/qjmed/hcs014. Epub 2012 Feb 12.

    PMID: 22331959BACKGROUND

  • Braun AB, Gibbons FK, Litonjua AA, Giovannucci E, Christopher KB. Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality. Crit Care Med. 2012 Jan;40(1):63-72. doi: 10.1097/CCM.0b013e31822d74f3.

    PMID: 21926604BACKGROUND

  • Turkoglu M, Aygencel G, Dizbay M, Tuncel AF, Arslan Candir B, Deligoz Bildaci Y, Pasaoglu H. Is vitamin D deficiency associated with development of Acinetobacter baumannii infections in critically ill patients? J Crit Care. 2013 Oct;28(5):735-40. doi: 10.1016/j.jcrc.2013.03.017.

    PMID: 24018297BACKGROUND

  • Amrein K, Schnedl C, Holl A, Riedl R, Christopher KB, Pachler C, Urbanic Purkart T, Waltensdorfer A, Munch A, Warnkross H, Stojakovic T, Bisping E, Toller W, Smolle KH, Berghold A, Pieber TR, Dobnig H. Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial. JAMA. 2014 Oct 15;312(15):1520-30. doi: 10.1001/jama.2014.13204.

    PMID: 25268295BACKGROUND

  • Spriet I, Meersseman W, de Hoon J, von Winckelmann S, Wilmer A, Willems L. Mini-series: II. clinical aspects. clinically relevant CYP450-mediated drug interactions in the ICU. Intensive Care Med. 2009 Apr;35(4):603-12. doi: 10.1007/s00134-008-1383-2. Epub 2009 Jan 9.

    PMID: 19132344BACKGROUND

  • Michaud J, Naud J, Ouimet D, Demers C, Petit JL, Leblond FA, Bonnardeaux A, Gascon-Barre M, Pichette V. Reduced hepatic synthesis of calcidiol in uremia. J Am Soc Nephrol. 2010 Sep;21(9):1488-97. doi: 10.1681/ASN.2009080815. Epub 2010 Jul 1.

    PMID: 20595682BACKGROUND

  • McNally JD. Vitamin D as a modifiable risk factor in critical illness: questions and answers provided by observational studies. J Pediatr (Rio J). 2014 Mar-Apr;90(2):99-101. doi: 10.1016/j.jped.2013.12.002. Epub 2013 Dec 19. No abstract available.

    PMID: 24361295BACKGROUND

  • Amrein K, Sourij H, Wagner G, Holl A, Pieber TR, Smolle KH, Stojakovic T, Schnedl C, Dobnig H. Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study. Crit Care. 2011;15(2):R104. doi: 10.1186/cc10120. Epub 2011 Mar 28.

    PMID: 21443793BACKGROUND

  • Bacon CJ, Gamble GD, Horne AM, Scott MA, Reid IR. High-dose oral vitamin D3 supplementation in the elderly. Osteoporos Int. 2009 Aug;20(8):1407-15. doi: 10.1007/s00198-008-0814-9. Epub 2008 Dec 20.

    PMID: 19101755BACKGROUND

  • von Restorff C, Bischoff-Ferrari HA, Theiler R. High-dose oral vitamin D3 supplementation in rheumatology patients with severe vitamin D3 deficiency. Bone. 2009 Oct;45(4):747-9. doi: 10.1016/j.bone.2009.06.012. Epub 2009 Jun 17.

    PMID: 19539796BACKGROUND

  • Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. doi: 10.1056/NEJMra070553. No abstract available.

    PMID: 17634462BACKGROUND

  • Vieth R. Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards. J Nutr. 2006 Apr;136(4):1117-22. doi: 10.1093/jn/136.4.1117.

    PMID: 16549491BACKGROUND

  • Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010 May 12;303(18):1815-22. doi: 10.1001/jama.2010.594.

    PMID: 20460620BACKGROUND

  • Smith H, Anderson F, Raphael H, Maslin P, Crozier S, Cooper C. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial. Rheumatology (Oxford). 2007 Dec;46(12):1852-7. doi: 10.1093/rheumatology/kem240. Epub 2007 Nov 12.

    PMID: 17998225BACKGROUND

MeSH Terms

Conditions

Vitamin D DeficiencyCritical Illness

Interventions

CholecalciferolMilk

Condition Hierarchy (Ancestors)

AvitaminosisDeficiency DiseasesMalnutritionNutrition DisordersNutritional and Metabolic DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

CholestenesCholestanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSterolsVitamin DSecosteroidsMembrane LipidsLipidsBeveragesDiet, Food, and NutritionPhysiological PhenomenaDairy ProductsFoodFood and Beverages

Study Officials

  • Asiah S Rugaan, MD, MRCP

    King Abdullah Medical City Makkah

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Consultant and Head of Department - Intensive Care Unit

Study Record Dates

First Submitted

August 7, 2016

First Posted

August 16, 2016

Study Start

August 27, 2017

Primary Completion

November 9, 2019

Study Completion

November 9, 2019

Last Updated

June 18, 2020

Record last verified: 2020-06

Locations

SA(1)