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Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET)

Primary Purpose

Acute Respiratory Distress Syndrome, Vitamin D Deficiency, Critical Illness

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Vitamin D3
Placebo
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring ARDS, Vitamin D

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Intention to admit to ICU from emergency department, hospital ward, operating room, or outside facility

  3. One or more of the following acute risk factors for ARDS and mortality contributing directly to the need for ICU admission:

    Pulmonary

    1. Pneumonia
    2. Aspiration
    3. Smoke Inhalation
    4. Lung contusion
    5. Mechanical ventilation for acute hypoxemic or hypercarbic respiratory failure Extra-Pulmonary
    6. Shock
    7. Sepsis
    8. Pancreatitis
  4. Vitamin D deficiency (screening 25OHD level <20 ng/mL)

Exclusion Criteria:

  1. Inability to obtain informed consent
  2. Unable to randomize within 12 hours of ICU admission decision
  3. Unable to take study medication by mouth or enteral tube
  4. Baseline serum calcium >10.2 mg/dL (2.54 mmol/L) or ionized calcium >5.2 mg/dL (1.30 mmol/L)
  5. Known kidney stone in past year or history of multiple (>1) prior kidney stone episodes
  6. Decision to withhold or withdraw life-sustaining treatment (patients are still eligible if they are committed to full support except cardiopulmonary resuscitation if a cardiac arrest occurs)
  7. Expect <48 hour survival
  8. If no other risk factors present, a) mechanical ventilation primarily for airway protection, pain/agitation control, or procedure; or b) elective surgical patients with routine postoperative mechanical ventilation; or c) anticipated mechanical ventilation duration <24 hours; or d) chronic/home mechanical ventilation for chronic lung or neuromuscular disease (non-invasive ventilation used solely for sleep-disordered breathing is not an exclusion).
  9. Prisoner
  10. Pregnancy

Sites / Locations

  • UCSF Fresno
  • Ronald Reagan UCLA Medical Center
  • UC Davis Medical Center
  • UCSF Medical Center
  • Stanford University
  • Medical Center of Aurora
  • University of Colorado Hospital
  • St. Joseph Hospital
  • Denver Health Medical Center
  • Swedish Medical Center
  • IU Health Methodist Hospital
  • University of Kentucky
  • University Medical Center
  • Maine Medical Center
  • Tufts Medical Center
  • Brigham and Women's Hospital
  • Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • Baystate Medical Center
  • St. Vincent's Hospital
  • University of Michigan Medical Center
  • Henry Ford Medical Center
  • University of Mississippi Medical Center
  • Montefiore Medical Center
  • Mt. Sinai Hospital
  • Wake Forest Baptist Medical Center
  • Summa Akron City Hospital
  • University of Cincinnati Medical Center
  • Cleveland Clinic Foundation
  • OSU Hospital East Campus
  • Ohio State University Wexner Medical Center
  • Providence Portland Medical Center
  • Oregon Health and Science University
  • Penn State Hershey Medical Center
  • UPMC Presbyterian/Mercy/Shadyside
  • Vanderbilt University Medical Center
  • Intermountain Medical Center
  • McKay-Dee Hospital
  • Utah Valley Regional Medical Center
  • University of Utah Hospital
  • LDS Hospital
  • University of Virginia Health System
  • VCU Medical Center
  • Harborview Medical Center
  • University of Washington Medical Center
  • Swedish Hospital Cherry Hill
  • Swedish Hospital First Hill

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

High dose vitamin D formulation

Placebo

Arm Description

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Outcomes

Primary Outcome Measures

All-cause, All-location Mortality to Day 90
Vital status of the patient at day 90 was determined using any of the following methods: medical record review, phone calls to patient, proxy or healthcare facility, review of obituaries, or information from the Centers for Disease Control and Prevention's National Death Index (NDI).

Secondary Outcome Measures

All-cause, All Location Mortality to Day 28
This variable was calculated in participants who were reported alive at day 28. Vital status of the patient at day 28 was determined using any of the following methods: medical record review, phone calls to patient, proxy or healthcare facility, or review of obituaries.
Hospital Mortality to Day 90
Analysis of the number of participants who died prior to hospital discharge up to study day 90.
Alive and Home (Prior Level of Care) at Day 90
This endpoint is the count of participants who have survived and are present at home, defined as pre-hospitalization level of care, at day 90.
Hospital Length of Stay to Day 90
Number of days from enrollment to the day of study hospital discharge up to day 90. Only calculated for patients that survived through day 90.
Healthcare Facility Length of Stay to Day 90
Healthcare facility length of stay is the time spent in another hospital or healthcare facility (e.g. long-term acute care [LTAC] hospitals or acute rehabilitation/skilled nursing facility), for the subgroup of participants that were discharged to another healthcare facility after the initial hospitalization. This measure is defined as the number of days from initial hospital discharge to the first facility discharge to home (pre-hospitalization level of care) up to day 90. Healthcare facility LOS is zero for patients discharged to home (pre-hospitalization level of care) from the study hospital. This endpoint will be analyzed only in survivors using SACE methods because healthcare facility length of stay in those who die during the follow-up period is non-informative for this endpoint.
Ventilator-free Days (VFDs) to Day 28
In participants who survive 28 days, ventilator free days (VFDs) is defined as 28 minus duration of ventilation. Duration of ventilation is counted from the first study day of assisted breathing through the last day of assisted breathing provided the last day is prior to day 28. Or it is counted from the first study day of assisted breathing through day 28. For participants discharged with assisted ventilation prior to day 28, a phone call will be required to assess ventilator status at day 28. Participants discharged prior to day 28 (but not to home) on unassisted breathing will be assumed to remain on unassisted breathing through day 28. Isolated periods of ventilation briefer than 24 hours for surgical procedures and ventilation solely for sleep disordered breathing do not count towards duration of ventilation. In participants who never require assisted breathing, duration of ventilation is zero. Participants who do not survive 28 days will be assigned zero VFD.
Health-related Quality of Life by EuroQol (EQ-5D-5L)
Changes in Quality of life score by EuroQol from baseline to day 90. Change was calculated as the value at day 90 minus the value at baseline. The EuroQol score is based on 5 dimensions of perceived problems: Mobility, Self-Care, Anxiety/Depression, Pain/discomfort, and Usual Activities. Problems with each area are assigned a level from 1-5 with level 1 being no problem and level 5 indicating extreme problems. A unique health state score is defined by combining 1 level from each of the 5 dimensions. Responses can be used to calculate a health utility score55 associated with the given health state that ranges from -0.11 to 1.00 (higher scores are better; 1.00 is perfect health).
Number of Participants Who Developed (New) ARDS to Day 7
Presence of ARDS determined using the PaO2/FiO2 ratio or SpO2/FiO2 ratio (i.e., imputed P/F ratio) and chest x-ray confirmation. PaO2 = partial pressure of arterial oxygen; FiO2 = percentage of inspired oxygen; SpO2 = peripheral capillary oxygen saturation, an estimate of the amount of oxygen in the blood. For participants with P/F <300 or imputed P/F <300, FiO2 ≥40%, and PEEP ≥5 cm H2O, we determined if hypoxemia was valid, acute, and not fully explained by congestive heart failure (CHF) or fluid overload. PEEP = positive end expiatory pressure.
Severity of Acute Respiratory Distress Syndrome (ARDS)
Severity of ARDS is determined using the PaO2/FiO2 ratio or SpO2/FiO2 ratio and confirmation of ARDS through chest x-ray reviews. The breakout of mild to severe was categorized as P/F or imputed P/F ratio of 201-300 (mild), 100-200 (moderate), or less than 100 (severe). This physiologic outcome is one of three key organ systems (respiratory, renal, and cardiovascular) used to assess change in organ failure severity from randomization up to study day 7.
Worst Acute Kidney Injury (AKI)
This physiologic outcome is one of three key organ systems (respiratory, renal, and cardiovascular) used to assess change in organ failure severity from randomization up to study day 7. Worst AKI was determined by using highest daily creatinine values or new use of dialysis/ renal replacement therapy (chronic dialysis participants were excluded). Mild: On-study creatinine levels 1.5 times greater than baseline value or 0.3 mg/dL over the prehospital value. Moderate: On-study creatinine levels 2 times greater than the baseline pre-hospital value. Severe: On-study creatinine creatinine levels are 3 times greater than baseline prehospital value, or the on-study creatinine level is over 4 mg/dL with an acute (1 day) 0.5 mg/dL rise, or participant is on new renal replacement therapy.
New Renal Replacement Therapy (RRT)
Participants who were on chronic dialysis at baseline were excluded from the analysis. Participants who started renal replacement therapy on a study day after day 0 and inclusive of day 7 were considered as having new renal replacement therapy. Those who have never started renal replacement therapy over days 0-7 were considered as not having new renal replacement therapy.
Highest Creatinine Levels
The highest recorded creatinine values is taken from available levels reported across the 7 study days for each patient.
New Vasopressor Use to Day 7
The number of subjects in each arm that are started on a vasopressor after randomization up to study day 7.
Highest Cardiovascular SOFA (Sepsis Related Organ Failure Assessment) Score
Cardiovascular score of the Organ SOFA score was used: Score = 0: MAP* >= 70 mmHg and No Drug; Score = 1: MAP < 70 mmHg and No Drug; Score = 2: (Any MAP) ( dopamine<=5 OR any dobutamine ) AND no other drugs (include neosynephrine vasopressin); Score = 3: (Any MAP) 5 < dopamine <= 15 OR epinephrine <= 0.1 OR norepinephrine <= 0.1 OR neosynephrine <=0.22 OR any dose vasopressin; Score = 4: (Any MAP) dopamine > 15 OR epinephrine > 0.1 OR norepinephrine > 0.1 OR neosynephrine > 0.22 * MAP = mean arterial pressure
25OHD Levels at Day 3
Baseline levels will be measured using LC/MS/MS methods (all randomized participants) and at day 3 (the first 300 randomized participants only).
Highest Total Calcium to Day 14
Clinically available serum or ionized Ca levels were obtained through day 14 for all randomized patients. This time frame was selected to align with the 25OHD half life of two weeks.
Highest Ionized Calcium to Day 14
Clinically available serum or ionized calcium levels through day 14 were collected for all randomized participants. This time frame was selected to align with the 25OHD half life of two weeks.
Hypercalcemia to Day 14
As the half-life of 25OHD is approximately 2 weeks, clinically available serum or ionized calcium levels through study day 14 were collected. The number of participants with hypercalcemia was reported.
Kidney Stones to Day 90
Incident of kidney stones determined by chart review at the end of hospitalization and by self-report at day 90 phone call in those discharged from the hospital prior to day 90.
Fall-related Fractures to Day 90
Incident of fall-related fractures will be determined by chart review at the end of hospitalization and by self-report at day 90 phone call for those discharged from the hospital prior to day 90. Most data suggest that high dose vitamin D in healthy outpatients may improve muscle function, balance, and bone mineral density, and thus decrease fall-related fractures, but other data suggest that high dose vitamin D supplementation may actually increase the incidence of falls/fractures. Because of this uncertainty and limited data in hospitalized patients, we assessed for incident of fall-related fractures.
Falls to Day 90
We assessed for incidence of falls by chart review at the end of hospitalization and by self-report at the 90 day phone call. Most data suggest that high dose vitamin D in healthy outpatients may improve muscle function, balance, and bone mineral density, and thus decrease fall-related fractures, but other data suggest that high dose vitamin D supplementation may actually increase the incidence of falls/fractures.

Full Information

First Posted
February 21, 2017
Last Updated
January 24, 2020
Sponsor
Massachusetts General Hospital
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT03096314
Brief Title
Vitamin D to Improve Outcomes by Leveraging Early Treatment
Acronym
VIOLET
Official Title
Vitamin D to Improve Outcomes by Leveraging Early Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
April 27, 2017 (Actual)
Primary Completion Date
December 11, 2018 (Actual)
Study Completion Date
December 11, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Patients screened as vitamin D deficient (<20 ng/mL) were randomized. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality.
Detailed Description
Primary Objective: To assess the efficacy and safety of early administration of vitamin D3 (cholecalciferol) in reducing mortality and morbidity for vitamin D deficient patients at high risk for Acute Respiratory Distress Syndrome (ARDS) and mortality. Primary Hypothesis: Early administration of vitamin D3 (cholecalciferol) will improve all-cause, all-location mortality to day 90 in vitamin D deficient patients at high risk for ARDS and mortality. Methods: Patients were recruited from the emergency departments (EDs), hospital wards, operating rooms, intensive care unites (ICUs) and other acute care areas of the participating PETAL Network Clinical Centers. Screening included a test for Vitamin D (25OHD) levels using either the hospital's clinical laboratory or an FDA-approved point-of-care device (FastPack IP, Qualigen Inc). Patients screened as vitamin D deficient (<20 ng/mL) were randomized. Half of the randomized patients received an early administration of high-dose vitamin D3 and the other half received a placebo. Both active and placebo products were given orally or via naso/orogastric tube. Rational: Vitamin D has pleiotropic roles in regulating immune function and maintaining epithelial surface integrity. Strong preclinical data support the protective role of vitamin D in regulating pulmonary inflammation and disruption of the alveolar-capillary membrane that are fundamental to ARDS pathogenesis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome, Vitamin D Deficiency, Critical Illness
Keywords
ARDS, Vitamin D

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1358 (Actual)

8. Arms, Groups, and Interventions

Arm Title
High dose vitamin D formulation
Arm Type
Active Comparator
Arm Description
A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.
Intervention Type
Drug
Intervention Name(s)
Vitamin D3
Other Intervention Name(s)
cholecalciferol
Intervention Description
540,000 IU vitamin D3 delivered as a single, liquid enteral dose administered either orally or via naso/orogastric tube
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
A single, liquid enteral dose identical in appearance and consistency to cholecalciferol administered either orally or via naso/orogastric tube.
Primary Outcome Measure Information:
Title
All-cause, All-location Mortality to Day 90
Description
Vital status of the patient at day 90 was determined using any of the following methods: medical record review, phone calls to patient, proxy or healthcare facility, review of obituaries, or information from the Centers for Disease Control and Prevention's National Death Index (NDI).
Time Frame
90 days after randomization
Secondary Outcome Measure Information:
Title
All-cause, All Location Mortality to Day 28
Description
This variable was calculated in participants who were reported alive at day 28. Vital status of the patient at day 28 was determined using any of the following methods: medical record review, phone calls to patient, proxy or healthcare facility, or review of obituaries.
Time Frame
Up to 28 days after randomization
Title
Hospital Mortality to Day 90
Description
Analysis of the number of participants who died prior to hospital discharge up to study day 90.
Time Frame
Up to 90 days after randomization
Title
Alive and Home (Prior Level of Care) at Day 90
Description
This endpoint is the count of participants who have survived and are present at home, defined as pre-hospitalization level of care, at day 90.
Time Frame
90 days post randomization
Title
Hospital Length of Stay to Day 90
Description
Number of days from enrollment to the day of study hospital discharge up to day 90. Only calculated for patients that survived through day 90.
Time Frame
90 days after randomization
Title
Healthcare Facility Length of Stay to Day 90
Description
Healthcare facility length of stay is the time spent in another hospital or healthcare facility (e.g. long-term acute care [LTAC] hospitals or acute rehabilitation/skilled nursing facility), for the subgroup of participants that were discharged to another healthcare facility after the initial hospitalization. This measure is defined as the number of days from initial hospital discharge to the first facility discharge to home (pre-hospitalization level of care) up to day 90. Healthcare facility LOS is zero for patients discharged to home (pre-hospitalization level of care) from the study hospital. This endpoint will be analyzed only in survivors using SACE methods because healthcare facility length of stay in those who die during the follow-up period is non-informative for this endpoint.
Time Frame
90 days after randomization
Title
Ventilator-free Days (VFDs) to Day 28
Description
In participants who survive 28 days, ventilator free days (VFDs) is defined as 28 minus duration of ventilation. Duration of ventilation is counted from the first study day of assisted breathing through the last day of assisted breathing provided the last day is prior to day 28. Or it is counted from the first study day of assisted breathing through day 28. For participants discharged with assisted ventilation prior to day 28, a phone call will be required to assess ventilator status at day 28. Participants discharged prior to day 28 (but not to home) on unassisted breathing will be assumed to remain on unassisted breathing through day 28. Isolated periods of ventilation briefer than 24 hours for surgical procedures and ventilation solely for sleep disordered breathing do not count towards duration of ventilation. In participants who never require assisted breathing, duration of ventilation is zero. Participants who do not survive 28 days will be assigned zero VFD.
Time Frame
28 days after randomization
Title
Health-related Quality of Life by EuroQol (EQ-5D-5L)
Description
Changes in Quality of life score by EuroQol from baseline to day 90. Change was calculated as the value at day 90 minus the value at baseline. The EuroQol score is based on 5 dimensions of perceived problems: Mobility, Self-Care, Anxiety/Depression, Pain/discomfort, and Usual Activities. Problems with each area are assigned a level from 1-5 with level 1 being no problem and level 5 indicating extreme problems. A unique health state score is defined by combining 1 level from each of the 5 dimensions. Responses can be used to calculate a health utility score55 associated with the given health state that ranges from -0.11 to 1.00 (higher scores are better; 1.00 is perfect health).
Time Frame
baseline to study day 90
Title
Number of Participants Who Developed (New) ARDS to Day 7
Description
Presence of ARDS determined using the PaO2/FiO2 ratio or SpO2/FiO2 ratio (i.e., imputed P/F ratio) and chest x-ray confirmation. PaO2 = partial pressure of arterial oxygen; FiO2 = percentage of inspired oxygen; SpO2 = peripheral capillary oxygen saturation, an estimate of the amount of oxygen in the blood. For participants with P/F <300 or imputed P/F <300, FiO2 ≥40%, and PEEP ≥5 cm H2O, we determined if hypoxemia was valid, acute, and not fully explained by congestive heart failure (CHF) or fluid overload. PEEP = positive end expiatory pressure.
Time Frame
Up to 7 days after randomization
Title
Severity of Acute Respiratory Distress Syndrome (ARDS)
Description
Severity of ARDS is determined using the PaO2/FiO2 ratio or SpO2/FiO2 ratio and confirmation of ARDS through chest x-ray reviews. The breakout of mild to severe was categorized as P/F or imputed P/F ratio of 201-300 (mild), 100-200 (moderate), or less than 100 (severe). This physiologic outcome is one of three key organ systems (respiratory, renal, and cardiovascular) used to assess change in organ failure severity from randomization up to study day 7.
Time Frame
7 days after randomization
Title
Worst Acute Kidney Injury (AKI)
Description
This physiologic outcome is one of three key organ systems (respiratory, renal, and cardiovascular) used to assess change in organ failure severity from randomization up to study day 7. Worst AKI was determined by using highest daily creatinine values or new use of dialysis/ renal replacement therapy (chronic dialysis participants were excluded). Mild: On-study creatinine levels 1.5 times greater than baseline value or 0.3 mg/dL over the prehospital value. Moderate: On-study creatinine levels 2 times greater than the baseline pre-hospital value. Severe: On-study creatinine creatinine levels are 3 times greater than baseline prehospital value, or the on-study creatinine level is over 4 mg/dL with an acute (1 day) 0.5 mg/dL rise, or participant is on new renal replacement therapy.
Time Frame
Up to 7 days after randomization
Title
New Renal Replacement Therapy (RRT)
Description
Participants who were on chronic dialysis at baseline were excluded from the analysis. Participants who started renal replacement therapy on a study day after day 0 and inclusive of day 7 were considered as having new renal replacement therapy. Those who have never started renal replacement therapy over days 0-7 were considered as not having new renal replacement therapy.
Time Frame
Up to 7 days after randomization
Title
Highest Creatinine Levels
Description
The highest recorded creatinine values is taken from available levels reported across the 7 study days for each patient.
Time Frame
Up to 7 days after randomization
Title
New Vasopressor Use to Day 7
Description
The number of subjects in each arm that are started on a vasopressor after randomization up to study day 7.
Time Frame
Up to 7 days after randomization
Title
Highest Cardiovascular SOFA (Sepsis Related Organ Failure Assessment) Score
Description
Cardiovascular score of the Organ SOFA score was used: Score = 0: MAP* >= 70 mmHg and No Drug; Score = 1: MAP < 70 mmHg and No Drug; Score = 2: (Any MAP) ( dopamine<=5 OR any dobutamine ) AND no other drugs (include neosynephrine vasopressin); Score = 3: (Any MAP) 5 < dopamine <= 15 OR epinephrine <= 0.1 OR norepinephrine <= 0.1 OR neosynephrine <=0.22 OR any dose vasopressin; Score = 4: (Any MAP) dopamine > 15 OR epinephrine > 0.1 OR norepinephrine > 0.1 OR neosynephrine > 0.22 * MAP = mean arterial pressure
Time Frame
Up to 7 days after randomization
Title
25OHD Levels at Day 3
Description
Baseline levels will be measured using LC/MS/MS methods (all randomized participants) and at day 3 (the first 300 randomized participants only).
Time Frame
3 days after randomization
Title
Highest Total Calcium to Day 14
Description
Clinically available serum or ionized Ca levels were obtained through day 14 for all randomized patients. This time frame was selected to align with the 25OHD half life of two weeks.
Time Frame
14 days after randomization
Title
Highest Ionized Calcium to Day 14
Description
Clinically available serum or ionized calcium levels through day 14 were collected for all randomized participants. This time frame was selected to align with the 25OHD half life of two weeks.
Time Frame
up to 14 days after randomization
Title
Hypercalcemia to Day 14
Description
As the half-life of 25OHD is approximately 2 weeks, clinically available serum or ionized calcium levels through study day 14 were collected. The number of participants with hypercalcemia was reported.
Time Frame
up to 14 days after randomization
Title
Kidney Stones to Day 90
Description
Incident of kidney stones determined by chart review at the end of hospitalization and by self-report at day 90 phone call in those discharged from the hospital prior to day 90.
Time Frame
90 days after randomization
Title
Fall-related Fractures to Day 90
Description
Incident of fall-related fractures will be determined by chart review at the end of hospitalization and by self-report at day 90 phone call for those discharged from the hospital prior to day 90. Most data suggest that high dose vitamin D in healthy outpatients may improve muscle function, balance, and bone mineral density, and thus decrease fall-related fractures, but other data suggest that high dose vitamin D supplementation may actually increase the incidence of falls/fractures. Because of this uncertainty and limited data in hospitalized patients, we assessed for incident of fall-related fractures.
Time Frame
90 days after randomization
Title
Falls to Day 90
Description
We assessed for incidence of falls by chart review at the end of hospitalization and by self-report at the 90 day phone call. Most data suggest that high dose vitamin D in healthy outpatients may improve muscle function, balance, and bone mineral density, and thus decrease fall-related fractures, but other data suggest that high dose vitamin D supplementation may actually increase the incidence of falls/fractures.
Time Frame
90 days post randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years Intention to admit to ICU from emergency department, hospital ward, operating room, or outside facility One or more of the following acute risk factors for ARDS and mortality contributing directly to the need for ICU admission: Pulmonary Pneumonia Aspiration Smoke Inhalation Lung contusion Mechanical ventilation for acute hypoxemic or hypercarbic respiratory failure Extra-Pulmonary Shock Sepsis Pancreatitis Vitamin D deficiency (screening 25OHD level <20 ng/mL) Exclusion Criteria: Inability to obtain informed consent Unable to randomize within 12 hours of ICU admission decision Unable to take study medication by mouth or enteral tube Baseline serum calcium >10.2 mg/dL (2.54 mmol/L) or ionized calcium >5.2 mg/dL (1.30 mmol/L) Known kidney stone in past year or history of multiple (>1) prior kidney stone episodes Decision to withhold or withdraw life-sustaining treatment (patients are still eligible if they are committed to full support except cardiopulmonary resuscitation if a cardiac arrest occurs) Expect <48 hour survival If no other risk factors present, a) mechanical ventilation primarily for airway protection, pain/agitation control, or procedure; or b) elective surgical patients with routine postoperative mechanical ventilation; or c) anticipated mechanical ventilation duration <24 hours; or d) chronic/home mechanical ventilation for chronic lung or neuromuscular disease (non-invasive ventilation used solely for sleep-disordered breathing is not an exclusion). Prisoner Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boyd Taylor Thompson, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSF Fresno
City
Fresno
State/Province
California
ZIP/Postal Code
93701
Country
United States
Facility Name
Ronald Reagan UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UC Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UCSF Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Medical Center of Aurora
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
St. Joseph Hospital
City
Del Norte
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Denver Health Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Facility Name
Swedish Medical Center
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
IU Health Methodist Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Kentucky
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40506
Country
United States
Facility Name
University Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Maine Medical Center
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02214
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Baystate Medical Center
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Facility Name
St. Vincent's Hospital
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01608
Country
United States
Facility Name
University of Michigan Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Henry Ford Medical Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48025
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Mt. Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Summa Akron City Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44304
Country
United States
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
OSU Hospital East Campus
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43203
Country
United States
Facility Name
Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Providence Portland Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Penn State Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
UPMC Presbyterian/Mercy/Shadyside
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37221
Country
United States
Facility Name
Intermountain Medical Center
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
McKay-Dee Hospital
City
Ogden
State/Province
Utah
ZIP/Postal Code
84403
Country
United States
Facility Name
Utah Valley Regional Medical Center
City
Provo
State/Province
Utah
ZIP/Postal Code
84604
Country
United States
Facility Name
University of Utah Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
LDS Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84143
Country
United States
Facility Name
University of Virginia Health System
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
VCU Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Harborview Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Swedish Hospital Cherry Hill
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
Swedish Hospital First Hill
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Data will be collected electronically and stored at the Clinical Coordinating Center at Massachusetts General Hospital (MGH). A de-identified database of all data will be available for use 3 years after the primary publication. Data can be accessed at that point via the National Heart Lung Blood Institute (NHLBI) BioLINCC data and biospecimen repository.
Citations:
PubMed Identifier
31826336
Citation
National Heart, Lung, and Blood Institute PETAL Clinical Trials Network; Ginde AA, Brower RG, Caterino JM, Finck L, Banner-Goodspeed VM, Grissom CK, Hayden D, Hough CL, Hyzy RC, Khan A, Levitt JE, Park PK, Ringwood N, Rivers EP, Self WH, Shapiro NI, Thompson BT, Yealy DM, Talmor D. Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients. N Engl J Med. 2019 Dec 26;381(26):2529-2540. doi: 10.1056/NEJMoa1911124. Epub 2019 Dec 11.
Results Reference
derived
Links:
URL
http://petalnet.org
Description
Website for the PETAL Network

Learn more about this trial

Vitamin D to Improve Outcomes by Leveraging Early Treatment

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