Settings: multicenter, double-blind, phase 3 trial (apparently vitamin D worked in phase 2 trials).

• Patients:
  • 1059 patients were enrolled within 12 hours of ICU admission.  The patients had to have risk factors warranted ICU admisions (pneumonia, sepsis, mechanical ventilation, shock, pancreatitis, etc.).
  • Vitamin D deficiency was defined as plasma level < 20 ng/ml
• Intervention:
  • 531 patients received a single oral dose of 540,000 IU of vitamin D3 within 2 hours after randomization
• Comparison
  • 528 patients received placebo
• Outcome
  • 90-day all-cause mortality

Study Results:

• Total SOFA score was similar in both groups (5.6 vs. 5.4).               
• On day 3, mean plasma vitamin D was higher (47 ng/ml) in treatment group vs 11 ng/ml in placebo group
• 90-day all cause mortality was similar.  Treatment group was 23.5% vs. 20.6% for placebo (95% CI, −2.1 to 7.9; P = 0.26).
• Vitamin D-related adverse events were similar in both groups.

Discussion:

• This trial enrolled patients early in their critical illness compared to phase 2 trial which enrolled patients after 3 days in the ICU.
• This phase 3 trial also enrolled mostly medical-related illness, whereas 75% of patients in phase 2 had either surgical or neurology-related illnesses.

Conclusion:

Early administration of high dose vitamin D did not improve 90-day all cause mortality.

 

References

Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients.

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. N Engl J Med. 2019 Dec 26;381(26):2529-2540.