Vitamin D to Improve Outcomes by Leveraging Early Treatment

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 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.

Patients will be recruited from the EDs, hospital wards, operating rooms, ICUs and other
acute care areas of the PETAL Network Clinical Centers. Screening will include 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) will be randomized. Half of the randomized patients will receive an early
administration of high-dose vitamin D3 and the other half will receive a placebo (orally or
via naso/orogastric tube).

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.

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