Prospective, Randomized, Multicenter Trial of Aerosolized Albuterol Versus Placebo in Acute Lung Injury
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 282
- 试验地点
- 40
- 主要终点
- Number of Ventilator Free Days (VFD)
研究概览
简要总结
Acute Respiratory Distress Syndrome (ARDS) and a lesser condition that occurs prior to ARDS, Acute Lung Injury (ALI), are medical conditions that occur when there is severe inflammation and increased fluids (edema) in both lungs, making it hard for the lungs to function properly. Patients with these conditions require treatment that includes the use of a breathing machine (ventilator). The purpose of this study is to find out whether giving albuterol (a drug commonly used in asthmatics) or not giving albuterol to patients with ALI or ARDS makes a difference in how long it takes for a patient to be able to breath without the ventilator.
详细描述
Aerosolized beta-2 agonist therapy is anticipated to diminish the formation of lung edema, enhance clearance of lung edema and decrease pulmonary inflammation in patients with acute lung injury. Because beta-2 agonists have been shown to reduce permeability induced lung injury, it is anticipated that the severity of lung injury will be reduced by aerosolized beta-2 agonist therapy. The therapy may work by enhancing resolution of pulmonary edema by upregulating alveolar epithelial fluid transport mechanisms that will in turn enhance the clearance of alveolar edema. A reduction in the severity of lung injury and the quantity of alveolar edema should result in earlier extubation and more ventilator free days, improved pulmonary oxygen uptake, and improved lung compliance.
Study design: phase II/III prospective, randomized double-blind, placebo controlled trial.
- In Phase II, patients will be treated with aerosolized albuterol 5.0 mg vs. normal saline (n=40-50)administered every 4 hours for 10 days following randomization or until 24 hours following extubation, whichever occurs first. The protocol stipulates that the 5.0 mg dose will be reduced to 2.5 mg if patients exceed defined heart rate limits.
- In Phase III, the 5.0 mg dose will be used unless there is evidence that this dose has an unacceptable safety profile or dose reductions for tachycardia occur in a large fraction of patients. In that case, a lower dose of 2.5 mg will be used.
- Patients will be followed for 90 days or until discharge from the hospital to home with unassisted breathing whichever occurs first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 13 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must meet the following three criteria within a 24-hour period:
- •Acute onset of PaO2/FiO2 less than or equal to 300 (adjustments made for altitude where appropriate)
- •Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph
- •Requirement for positive pressure ventilation via endotracheal tube
- •No clinical evidence of left-sided cardiac failure to account for bilateral pulmonary infiltrates
排除标准
- •Greater than 48 hours since all inclusion criteria are met
- •Neuromuscular disease that impairs ability to ventilate without assistance, (e.g., cervical spinal cord injury at level C5 or higher spinal cord injury amyotrophic lateral sclerosis, Guillain-Barré syndrome or myasthenia gravis)
- •Pregnant or breast-feeding
- •Severe chronic respiratory disease (i.e., chronic hypercapnia [PaCO2 greater than 45 mmHg], chronic hypoxemia [PaO2 less than 55 mmHg on FiO2 = 0.21], hospitalization within the last 6 months for respiratory failure [PaCO2 greater than 50 mm Hg and/or PaO2 less than 55 mmHg on 0.21 FiO2], secondary polycythemia, severe pulmonary hypertension [mean PAP (pulmonary artery pressure) greater than 40 mmHg], or ventilator dependency)
- •Burns over greater than 40% of total body surface area
- •Cancer or other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
- •Allogeneic bone marrow transplant within the 5 years prior to study entry
- •Participant, surrogate, or physician is not committed to full support (Exception: a participant will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
- •Severe chronic liver disease (Child-Pugh score of 11-15)
- •Diffuse alveolar hemorrhage from vasculitis
- •Morbid obesity (greater than 1kg/cm body weight.)
- •Unwillingness or inability to utilize the ARDS network 6 ml / kg Predicted Body Weight (PBW) ventilation protocol
- •Moribund participant and is not expected to survive 24 hours
- •No intent to obtain central venous access for monitoring intravascular pressures
- •Contraindication to aerosolized albuterol (see Appendix A.8 of the protocol for more information)
- •Daily use (prior to study hospitalization) of inhaled beta agonist, corticosteroid, or oral leukotriene modifier
- •Unwillingness of primary physician to discontinue inpatient beta agonist use
- •Acute myocardial infarction or acute coronary syndrome within 30 days of study entry
- •Severe congestive heart failure (see Appendix A5 of the protocol for more information)
- •Participation in other experimental medication trial within 30 days of study entry with the exception of the ARDSNet pharmaconutrient nutrition trial (OMEGA)
- •Heart rate greater than 85% of maximal predicted heart rate (MHR85) as calculated by MHR85 = 85% x (220-age)
- •Currently receiving high frequency ventilation
研究组 & 干预措施
Albuterol Sulfate
干预措施: Albuterol Sulfate (Drug)
Albuterol Sulfate
干预措施: Mini-Bronchoalveolar Lavage (BAL) (Procedure)
Placebo
干预措施: Mini-Bronchoalveolar Lavage (BAL) (Procedure)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Ventilator Free Days (VFD)
时间窗: Determined 28 days after a subject entered the study
Ventilator-free days (VFDs) is defined as the number of days from randomization to Day 28 after achieving unassisted breathing for patients who maintained unassisted breathing for at least two consecutive calendar days. If a patient achieved unassisted breathing, subsequently required additional assisted breathing, and once again achieved unassisted breathing, we counted only the VFDs after beginning the final period of unassisted breathing. Patients who died before Day 28 were assigned zero VFDs.
次要结局
- Hospital Mortality to Day 60 in the Subset of Participants With ARDS(Determined 60 days after a subject entered the study)
- Ventilator Free Days to Day 28 in the Subset of Patients With Baseline Shock(Determined 28 days after a subject entered the study)
- Mortality Prior to Hospital Discharge With Unassisted Breathing to Day 60(Determined 60 days after a subject entered the study)
- Mortality Prior to Hospital Discharge With Unassisted Breathing to Day 90(Determined 90 days after a subject entered the study)
- Plasma Levels of IL-6 and IL-8 on Study Day 3(Measured at baseline and 3 days after randomization)
- Number of ICU-free Days at 28 Days After Randomization(Determined 28 days after a subject entered the study)
- Number of Organ Failure-free Days at Day 28 Following Randomization(Daily from baseline to study day 28)
- Ventilator Free Days to Day 28 in the Subset of Participants With ARDS(Determined 28 days after a subject entered the study)
- Hospital Mortality up to Day 60 in Subjects With Baseline Shock(Determined 60 days after a subject entered the study)