Prevention and Early Treatment of Acute Lung Injury (PETAL) Clinical Trials Network – Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET)
Note that you will be prompted to log in or register an account
Open BioLINCC Study See bottom of this webpage for request information
April 2017 – December 2018
Dataset(s) Last Updated
May 16, 2022
Clinical Trial URLs
Primary Publication URLs
Commercial Use Data Restrictions No
Data Restrictions Based On Area Of Research No
To evaluate the effect of short-term vitamin D supplementation on mortality among critically ill patients with a vitamin D deficiency.
Observational data indicate that vitamin D deficiency is common among critically ill patients and constitutes a potentially modifiable risk factor associated with longer lengths of stay in the hospital and intensive care unit (ICU), lung and other organ injury, prolonged mechanical ventilation, and death. In a previous phase 2 trial, vitamin D supplementation administered to vitamin D-deficient, critically ill patients was associated with lower observed mortality than placebo at 28 days and at 6 months. Because of the need for a larger, phase 3 trial, the PETAL-VIOLET study was initiated to determine if early administration of high-dose vitamin D3 would reduce all-cause mortality among critically ill patients with a vitamin D deficiency.
Eligible patients were vitamin D deficient adults with one or more acute risk factors for death or lung injury that contributed directly to the need for ICU admission (pneumonia, sepsis, shock, mechanical ventilation for acute respiratory failure, aspiration, smoke inhalation, pancreatitis, or lung contusion). Patients with a history of kidney stones or the presence of hypercalcemia at baseline were excluded.
1360 patients underwent randomization, 690 were assigned to the vitamin D group and 668 were assigned to the placebo group. Of the 1078 patients confirmed to have a vitamin D deficiency by liquid chromatography-tandem mass spectrometry (LC-MS-MS), 538 had been assigned to the vitamin D group and 540 had been assigned to the placebo group.
PETAL-VIOLET was a multicenter, double-blind, placebo-controlled, phase 3 trial. Patients were enrolled within 12 hours after the clinician’s decision to admit the patient to the ICU from the emergency department, hospital ward, operating room, or outside facility. Patients were tested for vitamin D deficiency, with a threshold of plasma 25-hydroxyvitamin D level of less than 20 ng per milliliter. Patients were randomly assigned in a 1:1 ratio, stratified according to site, to receive either a single enteral (administered orally or through a nasogastric or orogastric tube) dose of 540,000 IU of vitamin D3 or matched placebo, in liquid form, administered within 2 hours after randomization.
The primary end point was 90-day all-cause, all-location mortality in the primary analysis population (i.e., patients with vitamin D deficiency confirmed by LC-MS-MS). Secondary end points included hospital length of stay to day 90, ventilator-free days to day 28, and quality of life to day 90.
After the first interim analysis, the data and safety monitoring board recommended that the trial be stopped for futility.
A single 540,000 IU enteral dose of vitamin D3 administered early during critical illness rapidly corrected vitamin D deficiency but did not provide an advantage over placebo with respect to mortality or other clinically important end points.
National Heart, Lung, and Blood Institute PETAL Clinical Trials Network, Ginde AA, Brower RG, et al. Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients. N Engl J Med. 2019;381(26):2529-2540. doi:10.1056/NEJMoa1911124
Please note that researchers must be registered on this site to submit a request, and you will be prompted to log in. If you are not registered on this site, you can do so via the Request button. Registration is quick, easy and free.
Resources AvailableStudy Datasets Only
Persons using assistive technology may not be able to fully access information in the study documents. For assistance, Contact BioLINCC and include the web address and/or publication title in your message. If you need help accessing information in different file formats such as PDF, XLS, DOC, see Instructions for Downloading Viewers and Players.