Vitamin D to Improve Outcomes by Leveraging Early Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,358
- 试验地点
- 47
- 主要终点
- All-cause, All-location Mortality to Day 90
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •Smoke Inhalation
- •Lung contusion
- •Mechanical ventilation for acute hypoxemic or hypercarbic respiratory failure Extra-Pulmonary
- •Pancreatitis
- •Vitamin D deficiency (screening 25OHD level <20 ng/mL)
排除标准
- •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
- •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).
研究组 & 干预措施
High dose vitamin D formulation
A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.
干预措施: Vitamin D3 (Drug)
Placebo
A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.
干预措施: Placebo (Drug)
结局指标
主要结局
All-cause, All-location Mortality to Day 90
时间窗: 90 days after randomization
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).
次要结局
- All-cause, All Location Mortality to Day 28(Up to 28 days after randomization)
- Hospital Length of Stay to Day 90(90 days after randomization)
- Highest Cardiovascular SOFA (Sepsis Related Organ Failure Assessment) Score(Up to 7 days after randomization)
- Hospital Mortality to Day 90(Up to 90 days after randomization)
- New Renal Replacement Therapy (RRT)(Up to 7 days after randomization)
- Highest Creatinine Levels(Up to 7 days after randomization)
- New Vasopressor Use to Day 7(Up to 7 days after randomization)
- Hypercalcemia to Day 14(up to 14 days after randomization)
- Kidney Stones to Day 90(90 days after randomization)
- Healthcare Facility Length of Stay to Day 90(90 days after randomization)
- Alive and Home (Prior Level of Care) at Day 90(90 days post randomization)
- Severity of Acute Respiratory Distress Syndrome (ARDS)(7 days after randomization)
- Falls to Day 90(90 days post randomization)
- Ventilator-free Days (VFDs) to Day 28(28 days after randomization)
- Health-related Quality of Life by EuroQol (EQ-5D-5L)(baseline to study day 90)
- Number of Participants Who Developed (New) ARDS to Day 7(Up to 7 days after randomization)
- Worst Acute Kidney Injury (AKI)(Up to 7 days after randomization)
- 25OHD Levels at Day 3(3 days after randomization)
- Highest Total Calcium to Day 14(14 days after randomization)
- Highest Ionized Calcium to Day 14(up to 14 days after randomization)
- Fall-related Fractures to Day 90(90 days after randomization)
研究者
Boyd Taylor Thompson
Co-Prinicipal Investigator PETAL CCC
Massachusetts General Hospital