Vitamin D to Improve Outcomes by Leveraging Early Treatment
VIOLET
2 other identifiers
interventional
1,358
1 country
47
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Apr 2017
47 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 21, 2017
CompletedFirst Posted
Study publicly available on registry
March 30, 2017
CompletedStudy Start
First participant enrolled
April 27, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 11, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 11, 2018
CompletedResults Posted
Study results publicly available
January 27, 2020
CompletedJanuary 27, 2020
January 1, 2020
1.6 years
February 21, 2017
December 10, 2019
January 24, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
All-cause, All-location Mortality to Day 90
Vital status of the patient at day 90 was determined using any of the following methods: medical record review, phone calls to patient, proxy or healthcare facility, review of obituaries, or information from the Centers for Disease Control and Prevention's National Death Index (NDI).
90 days after randomization
Secondary Outcomes (21)
All-cause, All Location Mortality to Day 28
Up to 28 days after randomization
Hospital Mortality to Day 90
Up to 90 days after randomization
Alive and Home (Prior Level of Care) at Day 90
90 days post randomization
Hospital Length of Stay to Day 90
90 days after randomization
Healthcare Facility Length of Stay to Day 90
90 days after randomization
- +16 more secondary outcomes
Study Arms (2)
High dose vitamin D formulation
ACTIVE COMPARATORA single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.
Placebo
PLACEBO COMPARATORA single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.
Interventions
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.
Eligibility Criteria
You may qualify if:
- Age ≥ 18 years
- Intention to admit to ICU from emergency department, hospital ward, operating room, or outside facility
- One or more of the following acute risk factors for ARDS and mortality contributing directly to the need for ICU admission:
- Pulmonary
- Pneumonia
- Aspiration
- Smoke Inhalation
- Lung contusion
- Mechanical ventilation for acute hypoxemic or hypercarbic respiratory failure Extra-Pulmonary
- Shock
- Sepsis
- Pancreatitis
- Vitamin D deficiency (screening 25OHD level \<20 ng/mL)
You may not qualify if:
- Inability to obtain informed consent
- Unable to randomize within 12 hours of ICU admission decision
- Unable to take study medication by mouth or enteral tube
- Baseline serum calcium \>10.2 mg/dL (2.54 mmol/L) or ionized calcium \>5.2 mg/dL (1.30 mmol/L)
- Known kidney stone in past year or history of multiple (\>1) prior kidney stone episodes
- 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)
- Expect \<48 hour survival
- Prisoner
- Pregnancy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (47)
UCSF Fresno
Fresno, California, 93701, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095, United States
UC Davis Medical Center
Sacramento, California, 95817, United States
UCSF Medical Center
San Francisco, California, 94143, United States
Stanford University
Stanford, California, 94305, United States
Medical Center of Aurora
Aurora, Colorado, 80045, United States
University of Colorado Hospital
Aurora, Colorado, 80045, United States
St. Joseph Hospital
Del Norte, Colorado, 80218, United States
Denver Health Medical Center
Denver, Colorado, 80204, United States
Swedish Medical Center
Englewood, Colorado, 80113, United States
IU Health Methodist Hospital
Indianapolis, Indiana, 46202, United States
University of Kentucky
Lexington, Kentucky, 40506, United States
University Medical Center
New Orleans, Louisiana, 70112, United States
Maine Medical Center
Portland, Maine, 04102, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Massachusetts General Hospital
Boston, Massachusetts, 02214, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Baystate Medical Center
Springfield, Massachusetts, 01199, United States
St. Vincent's Hospital
Worcester, Massachusetts, 01608, United States
University of Michigan Medical Center
Ann Arbor, Michigan, 48109, United States
Henry Ford Medical Center
Detroit, Michigan, 48025, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Mt. Sinai Hospital
New York, New York, 10029, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157, United States
Summa Akron City Hospital
Akron, Ohio, 44304, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
OSU Hospital East Campus
Columbus, Ohio, 43203, United States
Ohio State University Wexner Medical Center
Columbus, Ohio, 43210, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
UPMC Presbyterian/Mercy/Shadyside
Pittsburgh, Pennsylvania, 15261, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37221, United States
Intermountain Medical Center
Murray, Utah, 84107, United States
McKay-Dee Hospital
Ogden, Utah, 84403, United States
Utah Valley Regional Medical Center
Provo, Utah, 84604, United States
University of Utah Hospital
Salt Lake City, Utah, 84132, United States
LDS Hospital
Salt Lake City, Utah, 84143, United States
University of Virginia Health System
Charlottesville, Virginia, 22903, United States
VCU Medical Center
Richmond, Virginia, 23298, United States
Harborview Medical Center
Seattle, Washington, 98104, United States
University of Washington Medical Center
Seattle, Washington, 98104, United States
Swedish Hospital Cherry Hill
Seattle, Washington, 98122, United States
Swedish Hospital First Hill
Seattle, Washington, 98122, United States
Related Publications (1)
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. Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients. N Engl J Med. 2019 Dec 26;381(26):2529-2540. doi: 10.1056/NEJMoa1911124. Epub 2019 Dec 11.
PMID: 31826336DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The Data and Safety Monitoring Board recommended that the trial be stopped at the first interim analysis when the primary outcome of the study crossed a protocol specified futility boundary. This adaptive design element resulted in a completed study.
Results Point of Contact
- Title
- Nancy Ringwood, CCC Project Manager
- Organization
- Massachusetts General Hospital
Study Officials
- PRINCIPAL INVESTIGATOR
Boyd Taylor Thompson, MD
Massachusetts General Hospital
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Co-Prinicipal Investigator PETAL CCC
Study Record Dates
First Submitted
February 21, 2017
First Posted
March 30, 2017
Study Start
April 27, 2017
Primary Completion
December 11, 2018
Study Completion
December 11, 2018
Last Updated
January 27, 2020
Results First Posted
January 27, 2020
Record last verified: 2020-01
Data Sharing
- IPD Sharing
- Will share
Data will be collected electronically and stored at the Clinical Coordinating Center at Massachusetts General Hospital (MGH). A de-identified database of all data will be available for use 3 years after the primary publication. Data can be accessed at that point via the National Heart Lung Blood Institute (NHLBI) BioLINCC data and biospecimen repository.