High Flow Nasal Cannula Therapy as an Adjuvant in the Treatment of Severe Sepsis. A Multicenter Parallel-group Randomized Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 39
- 试验地点
- 2
- 主要终点
- Mortality
研究概览
简要总结
Severe sepsis leads a high morbidity and mortality by causing organ damage at distance. The treatment relies on early antibiotic therapy and hemodynamic resuscitation. Hypothesis: high flow nasal cannula (HFNC) could reduce work of breathing and improve the outcome of patients with severe sepsis and peripheral perfusion. Objective: the aim of this study is to evaluate the efficacy of HFNC for improving sixty-day survival in patients with severe sepsis. Design: multicenter parallel-group randomized clinical trial. Method: 592 adult patients with a diagnosis of severe sepsis in the first 12 hours of admission in the Emergency Room will be randomly assigned to an experimental or control group. In the experimental group, HFNC will be administered until the resolution of sepsis or until required mechanical ventilation, either invasive or non-invasive. In the Control group, conventional oxygen will be administered, if required. Sixty-day survival will be the primary outcome. The study is powered to demonstrate an improvement in survival from 70% in control group up to 80% in the HFNC group. The secondary outcomes will be reducing the need for vital support (mechanical ventilation, dialysis, vasoactive drugs) and physiological (acidosis, clearance of lactate, SvO2 and SOFA). Statistical analysis: Kaplan-Meier curves and Cox proportional hazard models will be calculated for all-cause sixty-day survival. If the results are conclusive, they will have immediate application in medical practice.
详细描述
Severe sepsis is a syndrome associated with severe infections with a high morbidity and mortality. In its most severe form, septic shock still leads to an in-hospital mortality of up to 50%. The pathophysiology of severe sepsis / septic shock includes increased work of breathing to compensate for tissue hypoperfusion-induced metabolic acidosis. This exaggerated work of breathing requires increased consumption of oxygen by respiratory muscles, which calls for a greater percentage of the already insufficient cardiac output, which can aggravate tissue hypoperfusion.
In the last decade, high flow nasal cannula (HFNC) appeared as an alternative ventilatory support intermediate between conventional oxygen and mechanical ventilation. Among others (3-7), the investigators have also demonstrated their effectiveness in patients with respiratory failure of different etiologies (8-11). Patients treated with HFNC quickly show a reduction of respiratory rate and respiratory work, associated with an improvement of the functional residual capacity and gas exchange. The absence of significant side effects and low cost makes HFNC especially attractive as adjunctive medical treatment in severe sepsis.
Then, the hypothesis is that in patients with severe sepsis, high flow nasal cannula (HFNC) therapy could reduce work of breathing, which would allow a redistribution of cardiac output from the respiratory muscles to other organs, improving peripheral perfusion with minor injury of organs at distance, less multiorgan failure and improved survival. Therefore, the aim of this study is to evaluate the efficacy of HFNC for improving sixty-day survival in patients with severe sepsis. This study will also provide a detailed evaluation of the HFNC's effects on the need for vital support (mechanical ventilation, dialysis, vasoactive drugs) and physiological parameters (acidosis, clearance of lactate, SvO2 and SOFA).
DESIGN Prospective, multicenter, randomized, controlled trial in 592 patients with severe sepsis admitted into a network of 18 ICUs from university and community hospitals in Spain to define the role of high flow oxygen therapy, with one experimental arm that will receive high flow oxygen therapy and a control arm that will receive conventional oxygen therapy if required.
Patients who consent will be randomized in a 1:1 ratio to receive HFNC or conventional treatment, which consists of adding oxygen on nasal prongs or Venturi mask only if hypoxemia is detected as SpO2 < 92% by pulse oximetry.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients > 18 yr. with diagnostic criteria for severe sepsis, within 12 hours of admission in the Emergency Room, defined as hypotension after hemodynamic resuscitation, initial lactate > 4, or persistence of organ dysfunction (oliguria < 0.5 ml/kg/h, cyanosis, or altered consciousness).(qSOFA 1, 2 or 3)
排除标准
- •Patients who require immediate ventilatory support both invasive and non-invasive, defined by severe hypoxemia (PaO2/FiO2 < 150), severe tachypnea (40 x') with signs of respiratory fatigue or low level of consciousness (Glasgow < 8).
- •Patients with limitation of the therapeutic effort or orders of not CPR.
- •Patients not susceptible to treatment with HFNC (facial trauma, tracheostomized, rejection of previous treatments with HFNC).
- •Participation in other clinical trials that may affect survival.
- •Home treatment with oxygen, CPAP or Non-invasive ventilation.
结局指标
主要结局
Mortality
时间窗: 60 day
60-day survival after enrollment
次要结局
- Dialysis support(up to 60-days)
- Lactate clearance(up to 60-days)
- Acidosis improvement(up to 60-days)
- Mechanical ventilation support(up to 60-days)
- Vasoactive drugs tappering(up to 60-days)
- Sequential Organ Failure Assessment(up to 60-days)
- Central Venous Oxygen Saturation (SatVO2)(up to 60-days)
研究者
Rafael Fernandez
Director. Critical Care Department
Althaia Xarxa Assistencial Universitària de Manresa