Prevention and Early Treatment of Acute Lung Injury (PETAL) Network – Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET)

HLB02602222a

PETAL-VIOLET

False

Respiratory Distress Syndrome

Respiratory Distress Syndrome, Newborn

Acute Lung Injury

Vitamin D Deficiency

Critical Illness

Lung Diseases

Respiratory Tract Diseases

Respiration Disorders

Infant, Premature, Diseases

Infant, Newborn, Diseases

Lung Injury

Disease Attributes

Pathologic Processes

Avitaminosis

Deficiency Diseases

Malnutrition

Nutrition Disorders

Vitamin D

Cholecalciferol

Vitamins

Micronutrients

Physiological Effects of Drugs

Bone Density Conservation Agents

Calcium-Regulating Hormones and Agents

Released

True

True

Coded

https://petalnet.org/studies.html

False

Clinical Trial

Open BioLINCC Study

Adult

Drug: Vitamin D3

Drug: Placebo

2022-05-16

2022-12-06

2022-05-11

2022-12-06

April 2017 – December 2018

DLD

Lung

non-HIV

non-COVID

None

None

No

No

Yes

No

Yes, For Some Specimens

Yes

Use of specimens in non-genetic research is unrestricted. Use of specimens in genetic research is tiered with respect to ARDS-related research and research related to other medical conditions.

Specimens may not be used directly to produce commercial products.

ARDS
Critical Illness
Vitamin D Deficiency

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

Plasma
Whole Blood

Prevention and Early Treatment of Acute Lung Injury (PETAL)