Phase 3
N=1,358
Vitamin D to Improve Outcomes by Leveraging Early Treatment
Acute Respiratory Distress Syndrome · Vitamin D Deficiency · Critical Illness
Bottom Line
View on ClinicalTrials.gov: NCT03096314 ↗Enrolled (actual)
1,358
Serious AEs
2.4%
Results posted
Jan 2020
Primary outcome: Primary: All-cause, All-location Mortality to Day 90 — 125; 109 Participants — p=0.26
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Vitamin D3 (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Massachusetts General Hospital
- Primary completion
- Dec 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY All-cause, All-location Mortality to Day 90 |
125; 109 | 0.26 |
| SECONDARY All-cause, All Location Mortality to Day 28 |
92; 69 | — |
| SECONDARY Hospital Mortality to Day 90 |
92; 72 | — |
| SECONDARY Alive and Home (Prior Level of Care) at Day 90 |
348; 345 | — |
| SECONDARY Hospital Length of Stay to Day 90 |
9.1; 10.4 | — |
| SECONDARY Healthcare Facility Length of Stay to Day 90 |
6.0; 8.1 | — |
| SECONDARY Ventilator-free Days (VFDs) to Day 28 |
21.3; 22.1 | — |
| SECONDARY Health-related Quality of Life by EuroQol (EQ-5D-5L) |
0.0; -0.0 | — |
| SECONDARY Number of Participants Who Developed (New) ARDS to Day 7 |
20; 17 | — |
| SECONDARY Severity of Acute Respiratory Distress Syndrome (ARDS) |
6; 4; 9; 12; 5; 1 | — |
| SECONDARY Worst Acute Kidney Injury (AKI) |
285; 297; 70; 77; 48; 52 | — |
| SECONDARY New Renal Replacement Therapy (RRT) |
20; 18 | — |
| SECONDARY Highest Creatinine Levels |
2.2; 2.1 | — |
| SECONDARY New Vasopressor Use to Day 7 |
43; 42 | — |
| SECONDARY Highest Cardiovascular SOFA (Sepsis Related Organ Failure Assessment) Score |
1.4; 1.3 | — |
| SECONDARY 25OHD Levels at Day 3 |
46.9; 11.4 | — |
| SECONDARY Highest Total Calcium to Day 14 |
8.9; 8.8 | 0.004 sig |
| SECONDARY Highest Ionized Calcium to Day 14 |
4.7; 4.6 | 0.67 |
| SECONDARY Hypercalcemia to Day 14 |
14; 11 | 0.51 |
| SECONDARY Kidney Stones to Day 90 |
0; 3 | 0.25 |
| SECONDARY Fall-related Fractures to Day 90 |
4; 2 | 0.69 |
| SECONDARY Falls to Day 90 |
36; 27 | 0.24 |
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.
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 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
Data sourced from ClinicalTrials.gov (NCT03096314). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.