Identifying and Preventing Ventilator Induced Diaphragm Dysfunction in Children
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 248
- 试验地点
- 2
- 主要终点
- Median Duration of Weaning
研究概览
简要总结
This study is a Phase II controlled clinical trial that will obtain comprehensive, serial assessments of respiratory muscle strength and architecture to understand the evolution of ventilator-induced respiratory muscle weakness in critically ill children, and test whether a novel computer-based approach (Real-time Effort Driven ventilator management (REDvent)) can preserve respiratory muscle strength and reduce time on MV. REDvent offers systematic recommendations to reduce controlled ventilation during the acute phase of MV, and uses real-time measures from esophageal manometry to adjust supported ventilator pressures such that patient effort of breathing remains in a normal range during the ventilator weaning phase. This phase II clinical trial is expected to enroll 276 children with pulmonary parenchymal disease, anticipated to be ventilated > 48 hrs. Patients will be randomized to REDvent-acute vs. usual care for the acute phase of MV (interval from intubation to first spontaneous breathing trial (SBT)). Patients in either group who fail their first Spontaneous Breathing Trial (SBT), will also be randomized to REDvent-weaning vs. usual care for the weaning phase of MV (interval from first SBT to passing SBT). The primary clinical outcome is length of weaning (time from first SBT until successful passage of an SBT or extubation (whichever comes first)). Mechanistic outcomes surround multi-modal serial measures of respiratory muscle capacity (PiMax), load (resistance, compliance), effort (esophageal manometry), and architecture (ultrasound) throughout the course of MV. Upon completion, this study will provide important information on the pathogenesis and timing of respiratory muscle weakness during MV in children and whether this weakness can be mitigated by promoting more normal patient effort during MV via the use of REDvent. This will form the basis for a larger, Phase III multi-center study, powered for key clinical outcomes such as 28-day Ventilator Free Days.
详细描述
Study Aims:
SA1: To determine if REDvent acute and/or weaning phase protocols can shorten the duration of weaning from MV (Primary outcome).
SA2: To determine if changes to direct measures of respiratory muscle strength, load, effort, and architecture throughout the duration of MV are related to weaning outcomes.
SA3: To determine if patient effort of breathing during both acute and weaning phases of MV is independently associated with the development of respiratory muscle weakness.
Study Design: Single-center randomized controlled trial (138 children per arm) using REDvent (intervention arm) as compared with usual care ventilator management including a standardized daily SBT (control arm). Acute phase randomization will occur upon study enrollment, and patients who fail the first SBT will undergo a weaning phase randomization. The investigators will obtain serial measurements of respiratory system capacity, load, effort of breathing, and diaphragm architecture throughout the course of MV.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
Analysis Blinded
入排标准
- 年龄范围
- 30 Days 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children > 1 month (>44 weeks CGA) and ≤ 18 years of age AND
- •Supported on mechanical ventilation with pulmonary parenchymal disease (i.e., pneumonia, bronchiolitis, Pediatric Acute Respiratory Distress Syndrome (PARDS)) with Oxygen Saturation Index (OSI) ≥ 5 or Oxygenation Index (OI) ≥) AND
- •Who are within 48 hours of initiation of invasive mechanical ventilation (allow for up to 72 hours for those transferred from another institution)
排除标准
- •Contraindications to use of an esophageal catheter (i.e. severe mucosal bleeding, nasal encephalocele, transphenoidal surgery) OR
- •Contraindications to use of RIP bands (i.e. omphalocele, chest immobilizer or cast) OR
- •Conditions precluding diaphragm ultrasound measurement (i.e. abdominal wall defects, pregnancy) OR
- •Conditions on enrollment that preclude conventional methods of weaning (i.e., status asthmaticus, severe lower airway obstruction, critical airway, intracranial hypertension, Extra Corporeal Life Support (ECLS), intubation for UAO, DNR, severe chronic respiratory failure, spinal cord injury above lumbar region, cyanotic heart disease (unrepaired or palliated)) OR
- •Primary Attending physician refuses (will be cleared with primary attending before approaching the patient).
结局指标
主要结局
Median Duration of Weaning
时间窗: First 28 days of Mechanical Ventilation
Time from first attempted SBT until SBT passage or extubation \[whichever comes first\]
次要结局
- Median Ventilator Free Days Between Acute Phase Randomization Groups(28 days)
- Number of Participants With Extubation Failure(Within 48 hours of extubation, assessed through study completion up to maximum of 90 Days)
- Number of Participants With Mortality(Through study completion up to maximum of 90 Days)
- Median Maximal Inspiratory Airway Pressure During Airway Occlusion (aPiMax) at First Spontaneous Breathing Trial During Acute Phase.(Assessed on the day of first spontaneous breathing trial up to 28 days)
- Median Maximal Inspiratory Esophageal Pressure During Airway Occlusion (ePiMax) During Acute Phase.(Assessed on the day of first spontaneous breathing trial up to 28 days)
- Median Ventilator Free Days Between Acute Phase Randomization Groups(28 days)
- Number of Participants With Extubation Failure(Within 48 hours of extubation, assessed through study completion up to maximum of 90 Days)
- Number of Participants With Mortality(Through study completion up to maximum of 90 Days)
- Median Maximal Inspiratory Airway Pressure During Airway Occlusion (aPiMax) at First Spontaneous Breathing Trial During Acute Phase.(Assessed on the day of first spontaneous breathing trial up to 28 days)
- Median Maximal Inspiratory Esophageal Pressure During Airway Occlusion (ePiMax) During Acute Phase.(Assessed on the day of first spontaneous breathing trial up to 28 days)
- Median Percentage Change in Diaphragm Thickness on Exhalation (Dte) From Baseline During Acute Phase(Each day from study initiation until extubation up to a maximum of 28 days)
研究者
Robinder Khemani
Principal Investigator
Children's Hospital Los Angeles