Dietary SupplementsPhase 3NCT04915963
Vitamin D Supplementation in Intensive Care Unit Patients
A Phase 3 study testing Vitamin D supplementation in people with Dietary Supplements and Intensive Care Unit, run by Association Tunisienne d'Etude & de Recherche sur l'Athérosclérose.
Trial summary
A randomized controlled trial is designed to investigate the safety and clinical efficacy of a mega dose of VD in patients admitted in intensive care unit (ICU). Patients will be randomly allocated to receive 400,000 IU of VD3 or placebo. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Dietary Supplements, Intensive Care Unit, Vitamin D Deficiency
- What is being tested?
- Vitamin D supplementation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 340 participants
- Where
- No sites listed yet
- Study dates
- 20 Jan 2016to 30 May 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- newly admitted (within 24 hours)
- over eighteen,
- able to receive medication orally or through nasogastric tube
- expected to stay more than 72 hours in ICU
- given consent
Who cannot join
- lack of patient's or relatives' consent
- expected short life or ICU stay (<48 hours)
- sepsis at admission
- kidney, liver or intestinal disease
- hypercalcemia (total calcium>10.6 mg/dL)
- history of a disorder associated with hypercalcemia (i.e., cancer, tuberculosis, sarcoidosis, hyperparathyroidism, nephrolithiasis)
Show all 9Show fewer
- treatment with immunotherapy or vitamin supplements within one year
- pregnant or breastfeeding women
- discharge from ICU or death within 72 hours of admission
About this study
Official title: Effect of a Single Mega-dose of Vitamin D3 Supplementation on Clinical Course in Non-deficient Patients Admitted in Intensive Care Unit
A randomized controlled trial is designed to investigate the safety and clinical efficacy of a mega dose of VD in patients admitted in intensive care unit (ICU). Patients will be randomly allocated to receive 400,000 IU of VD3 or placebo. They will be followed up until ICU discharge or death or the 15th day of ICU stay. Adverse events that occur during ICU stay is collected. Primary outcome is intensive care unit-acquired infection (ICU-AI), and secondary outcomes are septic shock, organ failure, and ICU-mortality. Plasma 25-hydroxyvitamin D is assessed at baseline and at the end of follow-up. Cox regression models will be applied to test how VD supplementation affects adverse outcomes while adjusting for confounders.
Read the detailed description
The randomized controlled trial aimed to investigate the safety and clinical efficacy of a single mega dose of vitamin D (VD) in patients admitted at intensive care unit (ICU).
Study participants: VD deficient ICU patients
Criteria of inclusion, patients:
- newly admitted (within 24 hours)
- over eighteen,
- able to receive medication orally or through nasogastric tube
- expected to stay more than 72 hours in ICU.
Criteria for non-inclusion and exclusion, patients:
- lack of patient's or relatives' consent
- expected short life or ICU stay (<48 hours)
- sepsis at admission
- kidney, liver or intestinal disease
- hypercalcemia (total calcium>10.6 mg/dL)
- history of a disorder associated with hypercalcemia (cancer, tuberculosis, sarcoidosis, hyperparathyroidism, nephrolithiasis)
- treatment with immunotherapy or vitamin supplements within one year
- pregnant or breastfeeding women
- discharge from ICU or death within 72 hours of admission
Study protocol
Patients will undergo physical examination with calculation of acute physiology and chronic assessment II (APACHE II) and sequential organ failure assessment (SOFA) scores. They will be randomly assigned to either VD or placebo group after stratification on gender, age and APACHE II:
- VD group, 170 patients will receive a single dose of 400,000 IU of VD3 orally or through nasogastric tube
- Placebo group, 170 patients will receive distilled water orally or through nasogastric tube.
The patients will followed up until ICU discharge or death or the 15th day of ICU stay, whichever occurs first and adverse events that occurred during ICU stay were collected.
Primary outcome: intensive care unit-acquired infection (ICU-AI), defined as an infection of blood stream, lower respiratory tract, urinary tract, skin/soft tissue or gastrointestinal tract, which was not present within the first 48 hours of admission into the ICU.
Secondary outcomes: urinary calcium:creatinine ratio as surrogate for VD toxicity, septic shock, organ failure, ICU-mortality.
Plasma 25-hydroxyvitamin D (25-OHD) will be assessed at baseline and the end of follow-up using immunoassay.
Cox regression models will be applied to test how VD supplementation affects adverse events and ICU-mortality while adjusting for confounders.
Hypothesis. Recovering an adequate VD status might reduce poor outcome, especially infectious outcomes in ICU patients.
- Being tested
- Vitamin D supplementation
- Keywords
- Critically ill, Intensive care unit, Vitamin D deficiencies
- Medical subject headings
- Vitamin D Deficiency, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin D supplementationDietary supplement
Patients are randomized to receive vitamin D or placebo and followed up for 15 days at maximum to investigate the safety and clinical efficacy of the supplements
| Study group | Role | What they receive |
|---|---|---|
| vitamin D group | Experimental | 170 patients receiving a single dose of 400,000 IU of VD3 (2 vials of 200,000 IU VD3; B.O.N., BOUCHARA RECORDATI) orally or through a nasogastric tube Receives: Dietary Supplement: Vitamin D supplementation |
| Placebo group | Sham comparator | 170 patients receiving distilled water (2 vials of 1 ml distilled water) orally or through a nasogastric tube Receives: Dietary Supplement: Vitamin D supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of intensive care unit-acquired infection (ICU-AI)
Infection of blood stream, lower respiratory tract, urinary tract, skin/soft tissue or gastrointestinal tract, which was not present within the first 48 hours of admission into the ICU, which occur during the ICU stay.
Measured: 15 days
Secondary outcomes (4)
urinary calcium:creatinine ratio
used as a surrogate for VD toxicity
Measured: 15 days
Rate of septic shock
persisting hypotension requiring vasopressors to maintain a mean arterial pressure of<65 mm Hg and a serum lactate level >2 mmol/L despite adequate volume resuscitation .
Measured: 15 days
Rate of organ failure
acute change in sequential organ failure assessment (SOFA) score of 2 points or greater secondary to infection
Measured: 15 days
Rate of ICU-mortality
Death within the ICU
Measured: 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2021
- Study start20 Jan 2016
- Primary completion10 Mar 2019
- Study completion30 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Dietary SupplementsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 340 participants (actual)
Sponsor and investigators
- Lead sponsor
- Association Tunisienne d'Etude & de Recherche sur l'Athérosclérose
- Sponsor type
- University, hospital or other
- Collaborators
- Faculty of Medicine of Tunis, Rabta University Hospital
- Responsible party
- Principal investigator, Amani Kallel, Association Tunisienne d'Etude & de Recherche sur l'Athérosclérose
- Investigators
- Moncef Feki, Professor, Study director, Rabta University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04915963
- Sponsor's protocol ID
- HR-2015/08
- Status last verified
- Jun 2021
- First submitted
- 1 Jun 2021
- Last updated
- 18 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. doi: 10.1056/NEJMra070553. No abstract available.
PubMed 17634462Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998 Mar 19;338(12):777-83. doi: 10.1056/NEJM199803193381201.
PubMed 9504937Kvaran RB, Sigurdsson MI, Skarphedinsdottir SJ, Sigurdsson GH. Severe vitamin D deficiency is common in critically ill patients at a high northern latitude. Acta Anaesthesiol Scand. 2016 Oct;60(9):1289-96. doi: 10.1111/aas.12748. Epub 2016 Jun 12.
PubMed 27291260Leaf DE, Raed A, Donnino MW, Ginde AA, Waikar SS. Randomized controlled trial of calcitriol in severe sepsis. Am J Respir Crit Care Med. 2014 Sep 1;190(5):533-41. doi: 10.1164/rccm.201405-0988OC.
PubMed 25029202Amrein 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.
PubMed 25268295Kempker JA, West KG, Kempker RR, Siwamogsatham O, Alvarez JA, Tangpricha V, Ziegler TR, Martin GS. Vitamin D status and the risk for hospital-acquired infections in critically ill adults: a prospective cohort study. PLoS One. 2015 Apr 7;10(4):e0122136. doi: 10.1371/journal.pone.0122136. eCollection 2015.
PubMed 25849649Ala-Kokko TI, Mutt SJ, Nisula S, Koskenkari J, Liisanantti J, Ohtonen P, Poukkanen M, Laurila JJ, Pettila V, Herzig KH; FINNAKI Study Group. Vitamin D deficiency at admission is not associated with 90-day mortality in patients with severe sepsis or septic shock: Observational FINNAKI cohort study. Ann Med. 2016;48(1-2):67-75. doi: 10.3109/07853890.2015.1134807. Epub 2016 Jan 22.
PubMed 26800186Quraishi 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.
PubMed 26086941
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of a Single Mega-dose of Vitamin D3 Supplementation on Clinical Course in Non-deficient Patients Admitted in Intensive Care Unit
- ClinicalTrials.gov ID
- NCT04915963
- Acronym / sponsor ID
- HR-2015/08
- Keywords
- Critically ill, Intensive care unit, Vitamin D deficiencies
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 340 participants (actual)
- Lead sponsor
- Association Tunisienne d'Etude & de Recherche sur l'AthéroscléroseUniversity, hospital or other
- Collaborators
- Faculty of Medicine of Tunis, Rabta University Hospital
- Study start
- 20 Jan 2016 (actual)
- Primary completion
- 10 Mar 2019 (actual)
- Study completion
- 30 May 2019 (actual)
- First posted
- 7 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized controlled trial is designed to investigate the safety and clinical efficacy of a mega dose of VD in patients admitted in intensive care unit (ICU). Patients will be randomly allocated to receive 400,000 IU of VD3 or placebo. They will be followed up until ICU discharge or death or the 15th day of ICU stay. Adverse events that occur during ICU stay is collected. Primary outcome is intensive care unit-acquired infection (ICU-AI), and secondary outcomes are septic shock, organ failure, and ICU-mortality. Plasma 25-hydroxyvitamin D is assessed at baseline and at the end of follow-up. Cox regression models will be applied to test how VD supplementation affects adverse outcomes while adjusting for confounders.
Detailed description
The randomized controlled trial aimed to investigate the safety and clinical efficacy of a single mega dose of vitamin D (VD) in patients admitted at intensive care unit (ICU).
Study participants: VD deficient ICU patients
Criteria of inclusion, patients:
- newly admitted (within 24 hours)
- over eighteen,
- able to receive medication orally or through nasogastric tube
- expected to stay more than 72 hours in ICU.
Criteria for non-inclusion and exclusion, patients:
- lack of patient's or relatives' consent
- expected short life or ICU stay (<48 hours)
- sepsis at admission
- kidney, liver or intestinal disease
- hypercalcemia (total calcium>10.6 mg/dL)
- history of a disorder associated with hypercalcemia (cancer, tuberculosis, sarcoidosis, hyperparathyroidism, nephrolithiasis)
- treatment with immunotherapy or vitamin supplements within one year
- pregnant or breastfeeding women
- discharge from ICU or death within 72 hours of admission
Study protocol
Patients will undergo physical examination with calculation of acute physiology and chronic assessment II (APACHE II) and sequential organ failure assessment (SOFA) scores. They will be randomly assigned to either VD or placebo group after stratification on gender, age and APACHE II:
- VD group, 170 patients will receive a single dose of 400,000 IU of VD3 orally or through nasogastric tube
- Placebo group, 170 patients will receive distilled water orally or through nasogastric tube.
The patients will followed up until ICU discharge or death or the 15th day of ICU stay, whichever occurs first and adverse events that occurred during ICU stay were collected.
Primary outcome: intensive care unit-acquired infection (ICU-AI), defined as an infection of blood stream, lower respiratory tract, urinary tract, skin/soft tissue or gastrointestinal tract, which was not present within the first 48 hours of admission into the ICU.
Secondary outcomes: urinary calcium:creatinine ratio as surrogate for VD toxicity, septic shock, organ failure, ICU-mortality.
Plasma 25-hydroxyvitamin D (25-OHD) will be assessed at baseline and the end of follow-up using immunoassay.
Cox regression models will be applied to test how VD supplementation affects adverse events and ICU-mortality while adjusting for confounders.
Hypothesis. Recovering an adequate VD status might reduce poor outcome, especially infectious outcomes in ICU patients.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| vitamin D group | Experimental | Dietary Supplement: Vitamin D supplementation170 patients receiving a single dose of 400,000 IU of VD3 (2 vials of 200,000 IU VD3; B.O.N., BOUCHARA RECORDATI) orally or through a nasogastric tube |
| Placebo group | Sham comparator | Dietary Supplement: Vitamin D supplementation170 patients receiving distilled water (2 vials of 1 ml distilled water) orally or through a nasogastric tube |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- newly admitted (within 24 hours)
- over eighteen,
- able to receive medication orally or through nasogastric tube
- expected to stay more than 72 hours in ICU
- given consent
Key exclusion criteria (9 listed)
- lack of patient's or relatives' consent
- expected short life or ICU stay (<48 hours)
- sepsis at admission
- kidney, liver or intestinal disease
- hypercalcemia (total calcium>10.6 mg/dL)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin D supplementationPatients are randomized to receive vitamin D or placebo and followed up for 15 days at maximum to investigate the safety and clinical efficacy of the supplements | Dietary supplement | Placebo group, vitamin D group |
Primary outcome
Rate of intensive care unit-acquired infection (ICU-AI)
Time frame: 15 days
Infection of blood stream, lower respiratory tract, urinary tract, skin/soft tissue or gastrointestinal tract, which was not present within the first 48 hours of admission into the ICU, which occur during the ICU stay.
4 secondary outcomes
urinary calcium:creatinine ratio
Time frame: 15 days
Rate of septic shock
Time frame: 15 days
Rate of organ failure
Time frame: 15 days
Rate of ICU-mortality
Time frame: 15 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2021.
- Background: PubMed 17634462Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. doi: 10.1056/NEJMra070553. No abstract available.
- Background: PubMed 9504937Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998 Mar 19;338(12):777-83. doi: 10.1056/NEJM199803193381201.
- Background: PubMed 27291260Kvaran RB, Sigurdsson MI, Skarphedinsdottir SJ, Sigurdsson GH. Severe vitamin D deficiency is common in critically ill patients at a high northern latitude. Acta Anaesthesiol Scand. 2016 Oct;60(9):1289-96. doi: 10.1111/aas.12748. Epub 2016 Jun 12.
- Background: PubMed 25029202Leaf DE, Raed A, Donnino MW, Ginde AA, Waikar SS. Randomized controlled trial of calcitriol in severe sepsis. Am J Respir Crit Care Med. 2014 Sep 1;190(5):533-41. doi: 10.1164/rccm.201405-0988OC.
- Background: PubMed 25268295Amrein 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.
- Background: PubMed 25849649Kempker JA, West KG, Kempker RR, Siwamogsatham O, Alvarez JA, Tangpricha V, Ziegler TR, Martin GS. Vitamin D status and the risk for hospital-acquired infections in critically ill adults: a prospective cohort study. PLoS One. 2015 Apr 7;10(4):e0122136. doi: 10.1371/journal.pone.0122136. eCollection 2015.
- Background: PubMed 26800186Ala-Kokko TI, Mutt SJ, Nisula S, Koskenkari J, Liisanantti J, Ohtonen P, Poukkanen M, Laurila JJ, Pettila V, Herzig KH; FINNAKI Study Group. Vitamin D deficiency at admission is not associated with 90-day mortality in patients with severe sepsis or septic shock: Observational FINNAKI cohort study. Ann Med. 2016;48(1-2):67-75. doi: 10.3109/07853890.2015.1134807. Epub 2016 Jan 22.
- Background: PubMed 26086941Quraishi 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Moncef Feki, Professor study director
Rabta University Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vitamin D supplementation in people with Dietary Supplements and Intensive Care Unit, run by Association Tunisienne d'Etude & de Recherche sur l'Athérosclérose.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of intensive care unit-acquired infection (ICU-AI) (time frame: 15 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04915963, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2021.