Vitamin D to Improve Outcomes by Leveraging Early Treatment

NCT ID: NCT03096314

Last Updated: 2020-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1358 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-27
• Study Completion Date: 2018-12-11

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.

Detailed Description

Primary Objective: To assess the efficacy and safety of early administration of vitamin D3 (cholecalciferol) in reducing mortality and morbidity for vitamin D deficient patients at high risk for Acute Respiratory Distress Syndrome (ARDS) and mortality.

Primary Hypothesis: Early administration of vitamin D3 (cholecalciferol) will improve all-cause, all-location mortality to day 90 in vitamin D deficient patients at high risk for ARDS and mortality.

Methods: Patients were recruited from the emergency departments (EDs), hospital wards, operating rooms, intensive care unites (ICUs) and other acute care areas of the participating PETAL Network Clinical Centers. Screening included a test for Vitamin D (25OHD) levels using either the hospital's clinical laboratory or an FDA-approved point-of-care device (FastPack IP, Qualigen Inc). Patients screened as vitamin D deficient (<20 ng/mL) were randomized. Half of the randomized patients received an early administration of high-dose vitamin D3 and the other half received a placebo. Both active and placebo products were given orally or via naso/orogastric tube.

Rational: Vitamin D has pleiotropic roles in regulating immune function and maintaining epithelial surface integrity. Strong preclinical data support the protective role of vitamin D in regulating pulmonary inflammation and disruption of the alveolar-capillary membrane that are fundamental to ARDS pathogenesis.

Conditions

Acute Respiratory Distress Syndrome; Vitamin D Deficiency; Critical Illness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

High dose vitamin D formulation

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Group Type: ACTIVE_COMPARATOR

Vitamin D3

Intervention Type: DRUG

540,000 IU vitamin D3 delivered as a single, liquid enteral dose administered either orally or via naso/orogastric tube

Placebo

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

A single, liquid enteral dose identical in appearance and consistency to cholecalciferol administered either orally or via naso/orogastric tube.

Interventions

Vitamin D3

540,000 IU vitamin D3 delivered as a single, liquid enteral dose administered either orally or via naso/orogastric tube

Intervention Type: DRUG

Placebo

A single, liquid enteral dose identical in appearance and consistency to cholecalciferol administered either orally or via naso/orogastric tube.

Intervention Type: DRUG

Other Intervention Names

cholecalciferol

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Boyd Taylor Thompson

Co-Prinicipal Investigator PETAL CCC

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Boyd Taylor Thompson, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

UCSF Fresno

Fresno, California, United States

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

UC Davis Medical Center

Sacramento, California, United States

UCSF Medical Center

San Francisco, California, United States

Stanford University

Stanford, California, United States

Medical Center of Aurora

Aurora, Colorado, United States

University of Colorado Hospital

Aurora, Colorado, United States

St. Joseph Hospital

Del Norte, Colorado, United States

Denver Health Medical Center

Denver, Colorado, United States

Swedish Medical Center

Englewood, Colorado, United States

IU Health Methodist Hospital

Indianapolis, Indiana, United States

University of Kentucky

Lexington, Kentucky, United States

University Medical Center

New Orleans, Louisiana, United States

Maine Medical Center

Portland, Maine, United States

Tufts Medical Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Baystate Medical Center

Springfield, Massachusetts, United States

St. Vincent's Hospital

Worcester, Massachusetts, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Henry Ford Medical Center

Detroit, Michigan, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Mt. Sinai Hospital

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Summa Akron City Hospital

Akron, Ohio, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

OSU Hospital East Campus

Columbus, Ohio, United States

Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Providence Portland Medical Center

Portland, Oregon, United States

Oregon Health and Science University

Portland, Oregon, United States

Penn State Hershey Medical Center

Hershey, Pennsylvania, United States

UPMC Presbyterian/Mercy/Shadyside

Pittsburgh, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Intermountain Medical Center

Murray, Utah, United States

McKay-Dee Hospital

Ogden, Utah, United States

Utah Valley Regional Medical Center

Provo, Utah, United States

University of Utah Hospital

Salt Lake City, Utah, United States

LDS Hospital

Salt Lake City, Utah, United States

University of Virginia Health System

Charlottesville, Virginia, United States

VCU Medical Center

Richmond, Virginia, United States

Harborview Medical Center

Seattle, Washington, United States

University of Washington Medical Center

Seattle, Washington, United States

Swedish Hospital Cherry Hill

Seattle, Washington, United States

Swedish Hospital First Hill

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 31826336 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://petalnet.org

Website for the PETAL Network

Other Identifiers

1U01HL123009

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PETAL02VIOLET

Identifier Type: -

Identifier Source: org_study_id