Phase II/Phase III Study of the Effect of Combined High-frequency Oscillation and Tracheal Gas Insufflation on the Survival to Hospital Discharge of Patients With Severe Acute Respiratory Distress Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 124
- 试验地点
- 4
- 主要终点
- Survival to days 28 and 60 post-randomization, and to Hospital Discharge
研究概览
简要总结
The investigators have recently demonstrated the beneficial effects of combined high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) on the respiratory physiology [1,2] of patients with severe acute respiratory distress syndrome (ARDS) (NCT00416260). Preliminary short-term survival results were also encouraging. Consequently, in the present clinical trial, the investigators intend to increase the size of the studied population, in order to evaluate the effect of HFO-TGI on survival with adequate statistical power. Furthermore, the investigators intend to elucidate the mechanism of the HFO-TGI-related physiological benefit.
详细描述
BACKGROUND AND OBJECTIVES
The prognosis of ARDS still remains grave [3-7]. The primary objective of the present study, is to definitively determine the effect of HFO-TGI on the survival of patients with severe ARDS. Consequently, we will increase the size of the studied population (see also NCT00416260), in order to achieve sufficient statistical power. The secondary objective is to test the hypothesis that lung recruitment is the major underlying mechanism for the HFO-TGI-associated improvement in oxygenation [1,2] and respiratory compliance [2].
METHODS
Patients
The protocol has been approved by the Scientific Committees of Evaggelismos Hospital and of Larissa University Hospital. Informed consent will be requested from the next-of-kin of participation-eligible patients. Patients will be informed of the trial and their right to withdraw as soon as clinically feasible. Eligibility criteria are presented in the appropriate section of this report. In brief, the major inclusion criteria will comprise 1) early (diagnosis established within the preceding 72 h) ARDS according to the American-European Consensus Conference Definition [6]; 2) severe oxygenation disturbances {defined as PaO2/FiO2) < 150 mm Hg}, while ventilated with a positive end-expiratory pressure (PEEP) of ≥ 8 cm H2O (criterion for severe ARDS); and 3) age 18-75 years and body weight > 40 kg. Patient monitoring will include electrocardiographic lead II, hemodynamics {continuous intraarterial and central-venous pressure, and cardiac output/index by PICCO-plus (Pulsion Medical Systems, Munich, Germany)}, and peripheral oxygen saturation (SpO2). Deep sedation (propofol/midazolam) [8,9], analgesia (fentanyl/remifentanil) [9], and intermittent neuromuscular blockade (cisatracurium) [8,10] will be used.
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
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years
- •Body weight > 40 kg
- •Endotracheal intubation and mechanical ventilation
- •Diagnosis of ARDS established within preceding 72 h
- •Severe oxygenation disturbances: PaO2/FiO2 <150 mm Hg sustained for 12 h, despite being ventilated with PEEP ≥8 cm H2O
排除标准
- •Active air leak or recent severe air leak (severe air leak: > 1 chest tube per hemithorax with persistent gas leak for > 72 h)
- •Severe hemodynamic instability (i.e., systolic arterial pressure < 90 mm Hg despite volume loading and norepinephrine infusion at ≥ 0.5 μg/kg/min)
- •Significant heart disease (i.e., ejection fraction <40 %, and/or history of pulmonary edema, and/or active coronary ischemia or myocardial infarction)
- •Significant chronic obstructive pulmonary disease (COPD) or asthma {i.e., previous admissions for COPD/asthma, chronic corticosteroid therapy for COPD/asthma, and documented chronic CO2 retention leading to a baseline PaCO2 of > 50 mm Hg (for COPD)}
- •Uncontrollable intracranial hypertension (i.e., intracranial pressure >20 mm Hg despite deep sedation, analgesia, hyperosmolar therapy, and minute ventilation titrated to PaCO2 = 35 mm Hg)
- •Chronic Interstitial Lung Disease associated with bilateral pulmonary infiltrates
- •Lung biopsy or resection on current admission
- •Immunosuppression caused by
- •neutropenia [i.e., polymorphonuclear leukocyte count < 1,000/μL (1 x 1012/L)] after chemotherapy or bone marrow transplantation for hematologic cancers
- •corticosteroid or cytotoxic therapy for a nonmalignant disease
- •the acquired immunodeficiency syndrome
- •Inability to wean from prone positioning or inhaled nitric oxide
- •Pregnancy or morbid obesity (body mass index >40 kg/m2)
- •Enrollment in another interventional study
- •Crossover from the CMV-group to the HFO-TGI-group at > 72 h after the onset of the severe oxygenation disturbances
结局指标
主要结局
Survival to days 28 and 60 post-randomization, and to Hospital Discharge
时间窗: 28 days to more than 60 days post-randomization
次要结局
- Occurrence of barotrauma (i.e., any new pneumothorax, pneumomediastinum, or subcutaneous emphysema, or pneumatocele > 2 cm)(60 days post-randomization)
- Lung recruitment during the study-intervention period(8 days post-randomization)
- Evolution of Gas-exchange, Hemodynamics, and Respiratory Mechanics during the Study Intervention Period(8-10 days post-randomization)
- Ventilator Free Days(60 days post-randomization)
- Organ or System Failure Free Days(60 days post-randomization)
- Occurence of Tracheal Mucosal Injury due to use of Tracheal Gas Insufflation(8-10 days post-randomization)
研究者
Spyros D. Mentzelopoulos
Assistant Professor of Intensive Care Medicine
University of Athens