Vitamin D to Improve Outcomes by Leveraging Early Treatment
Condition: Acute Respiratory Distress Syndrome; Vitamin D Deficiency; Critical Illness
MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Vitamin D Deficiency; Critical Illness
Intervention: Vitamin D3; Placebo
Intervention description: 540,000 IU vitamin D3 delivered as a single, liquid enteral dose administered either orally or via naso/orogastric tube; A single, liquid enteral dose identical in appearance and consistency to cholecalciferol administered either orally or via naso/orogastric tube.
Intervention MeSH terms: Vitamin D; Cholecalciferol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1358.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ARDS; Vitamin D

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:

          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