The Association of Vitamin D Supplementation With the Outcome in Critically Ill Children

Critically Ill Clinical Trial

Official title:

The Association of Vitamin D Supplementation With the Outcome in Critically Ill Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04536831
• Other study ID #: MKA1
• Status: Completed
• Phase: Phase 4
• Start date: August 29, 2019
• Est. completion date: February 25, 2020

Study information

• Verified date: August 2020
• Source: King Edward Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Vitamin D deficiency is highly prevalent in critically ill adult and pediatric population that causes multiple adverse health outcomes including higher illness severity score, increased morbidity and mortality, multiple organ dysfunction, longer duration of Mechanical ventilation, longer duration of Oxygen therapy and increased length of stay (LOS) in PICU and hospital. Vitamin D deficiency is a modifiable risk factor that can be corrected with high dose of vitamin D supplementation to improve the clinical outcome.

This study is designed to determine whether random vitamin D supplementation within dose limits improves clinical outcomes in critically ill children.

Description:

Vitamin D is known for its role in bone metabolism and calcium haemostasis but it is also required for the optimal functioning of cardiovascular and innate immune systems.

As a pleiotropic hormone it has been increasingly implicated in proper functioning of multiple organs; its deficiency is associated with cardiovascular diseases, asthma, cancer, multiple sclerosis, diabetes and acute lower respiratory tract infections. Over one billion people are vitamin D deficient worldwide and in Pakistani population vitamin D deficiency is reported as high as 76% despite abundant sunshine.

Beside of ambulatory individuals, the patients presenting in intensive care units are also found Vitamin D deficient. In adult intensive care settings studies have shown vitamin D deficiency (VDD) present in 60% of critically ill adult patients.VDD is also very common in pediatric intensive care units (PICU) worldwide, ranging from 30 to 80%.

Although there is high prevalence of VDD in pediatric and adult population, but there is no uniform definition of VDD exists. Levels of active metabolite 1,25(OH)2D of Vitamin D at tissue level cannot be measured, however, patient's blood level of 25-hydroxy vitamin D is used to know vitamin D stores in the body. Patient with serum vitamin D level<20ng/ml is considered to be vitamin D deficient.

VDD is associated with clinically poor outcomes like increased duration of mechanical ventilation, increased length of hospital stay, Sepsis, Acute respiratory failure and mortality in critically ill patients.

The existing evidences suggest that Vitamin D3 supplementation enhances recovery from influenza, recurrent pneumonias and tuberculosis. Recently, an observational study of adult patients suggested that patients with VDD showed decrease in the odds of all cause-mortality when their Vitamin D status was improved before hospitalization.

A randomized study demonstrated that one time bolus dose of oral vitamin D supplementation caused decrease in mortality in a group of patients with severe VDD.

A significant literature is available that suggests vitamin D deficiency as a modifiable risk factor in PICU settings. The recognized importance of vitamin D to the health of multiple organ systems suggest that rapid normalization could represent a simple, inexpensive, and safe means of improving outcomes and reducing health care spending.

This study is designed to supplement large dose of vitamin D that may lead to fast correction of low vitamin D level in critically ill children and possibility of better clinical outcome. If such an association is established by this study, routine detection and use of Vitamin D might be recommended for critically ill children admitted to PICU.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: February 25, 2020
• Est. primary completion date: February 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 10 Years

Eligibility

Inclusion Criteria:

• Children of age 6 months to 10 years, either gender admitted in ICU for critical illness (on medical record) with PIM-2 score suggesting probability of mortality more than 50%.

Exclusion Criteria:

• Children with known adrenal, pituitary, hypothalamic or thyroid disease.

• Those who have complex congenital defects.

• Moribund at time of admission.

• Those who were expected to be care withdrawn.

• Patients who had received large dose regimen (200,000 IU or more) of vitamin D during the previous three months before admission.

Related Conditions & MeSH terms

• Critical Illness
• Critically Ill

Intervention

Drug:
• Vitamin D
Vitamin D will be given to group A selected by Lottery method
• Normal saline
Vitamin D will be given to group B slected by Lottery method

Locations

Country	Name	City	State
Pakistan	King Edward Medical University Lahore	Lahore	Punjab

Sponsors (2)

Lead Sponsor	Collaborator
Dr Mustahsin Khalil	King Edward Medical University

Country where clinical trial is conducted

Pakistan, 

References & Publications (16)

Amrein K, Litonjua AA, Moromizato T, Quraishi SA, Gibbons FK, Pieber TR, Camargo CA Jr, Giovannucci E, Christopher KB. Increases in pre-hospitalization serum 25(OH)D concentrations are associated with improved 30-day mortality after hospital admission: A cohort study. Clin Nutr. 2016 Apr;35(2):514-521. doi: 10.1016/j.clnu.2015.03.020. Epub 2015 Apr 14. — View Citation

Amrein K, Schnedl C, Holl A, Riedl R, Christopher KB, Pachler C, Urbanic Purkart T, Waltensdorfer A, Münch 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. Erratum in: JAMA. 2014 Nov 12;312(18):1932. — View Citation

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. — View Citation

Angurana SK. Serum Vitamin D Status and Outcome among Critically Ill Children Admitted to the Pediatric Intensive Care Unit in South India: Correspondence. Indian J Pediatr. 2016 Aug;83(8):910-1. doi: 10.1007/s12098-015-1992-z. Epub 2016 Jan 14. — View Citation

Balasubramanian S, Dhanalakshmi K, Amperayani S. Vitamin D deficiency in childhood-a review of current guidelines on diagnosis and management. Indian Pediatr. 2013 Jul;50(7):669-75. Review. — View Citation

Gandhi J, Sangareddi S, Varadarajan P, Suresh S. Pediatric index of mortality 2 score as an outcome predictor in pediatric Intensive Care Unit in India. Indian J Crit Care Med. 2013 Sep;17(5):288-91. doi: 10.4103/0972-5229.120320. — View Citation

Greenbaum LA. Rickets and Hypervitaminosis. In: Kliegman RM, Stanton BF, Geme III JW, Schor NF. (eds). Nelson Textbook Of Pediatrics. 20th ed. Philadelphia: Elsevier; 2016. p.331-38.

Han JE, Jones JL, Tangpricha V, Brown MA, Brown LAS, Hao L, Hebbar G, Lee MJ, Liu S, Ziegler TR, Martin GS. High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial. J Clin Transl Endocrinol. 2016 Jun;4:59-65. doi: 10.1016/j.jcte.2016.04.004. Epub 2016 May 5. — View Citation

Hossain N, Khanani R, Hussain-Kanani F, Shah T, Arif S, Pal L. High prevalence of vitamin D deficiency in Pakistani mothers and their newborns. Int J Gynaecol Obstet. 2011 Mar;112(3):229-33. doi: 10.1016/j.ijgo.2010.09.017. Epub 2011 Jan 17. — View Citation

Madden K, Feldman HA, Smith EM, Gordon CM, Keisling SM, Sullivan RM, Hollis BW, Agan AA, Randolph AG. Vitamin D deficiency in critically ill children. Pediatrics. 2012 Sep;130(3):421-8. doi: 10.1542/peds.2011-3328. Epub 2012 Aug 6. — View Citation

Mahmood K, Akhtar ST, Talib A, Haider I. Vitamin-D status in a population of healthy adults in Pakistan. Pak J Med Sci. 2009;25(4):545-50.

McNally D, Amrein K, O'Hearn K, Fergusson D, Geier P, Henderson M, Khamessan A, Lawson ML, McIntyre L, Redpath S, Weiler HA, Menon K; Canadian Critical Care Trials Group. Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study). Pilot Feasibility Stud. 2017 Dec 8;3:70. doi: 10.1186/s40814-017-0214-z. eCollection 2017. — View Citation

McNally JD, Iliriani K, Pojsupap S, Sampson M, O'Hearn K, McIntyre L, Fergusson D, Menon K. Rapid normalization of vitamin D levels: a meta-analysis. Pediatrics. 2015 Jan;135(1):e152-66. doi: 10.1542/peds.2014-1703. Epub 2014 Dec 15. — View Citation

McNally JD, Menon K, Chakraborty P, Fisher L, Williams KA, Al-Dirbashi OY, Doherty DR; Canadian Critical Care Trials Group. The association of vitamin D status with pediatric critical illness. Pediatrics. 2012 Sep;130(3):429-36. Epub 2012 Aug 6. — View Citation

Riaz H, Finlayson AE, Bashir S, Hussain S, Mahmood S, Malik F, Godman B. Prevalence of Vitamin D deficiency in Pakistan and implications for the future. Expert Rev Clin Pharmacol. 2016;9(2):329-38. doi: 10.1586/17512433.2016.1122519. Epub 2016 Jan 13. — View Citation

Williams S, Heuberger R. Outcomes of Vitamin D Supplementation in Adults Who are Deficient and Critically Ill: A Review of the Literature. Am J Ther. 2016 Nov/Dec;23(6):e1890-e1902. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death	Patient is declared dead by duty doctor	upto one month
Primary	Discharge	Patient became vitally stable and shifted out of PICU	upto one month
Secondary	Duration of O2 therapy	Total time that patient required O2	upto one month
Secondary	Duration of Mechanical ventilation	Total time of Mechanical ventilation required by the patient	upto one month
Secondary	Duration of PICU stay	Total Duration of stay in PICU	upto one month
Secondary	Duration of Hospital stay.	Total duration of Hospital stay in wards except PICU stay	upto one month