Identifying and Preventing Ventilator Induced Diaphragm Dysfunction in Children
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 248
- Locations
- 1
- Primary Endpoint
- Median Duration of Weaning
Study Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Single (Outcomes Assessor)
Masking Description
Analysis Blinded
Eligibility Criteria
- Ages
- 30 Days to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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)
Exclusion Criteria
- •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).
Arms & Interventions
REDvent-acute
Acute Phase: The acute phase is defined as the time from intubation until the patient meets weaning criteria, passes the initial oxygenation test (decrease PEEP to 5 cmH2O and FiO2 to 0.5, maintains SpO2 > 90%), and undergoes a Spontaneous Breathing Trial (SBT). Patients will be managed with pressure control plus pressure support ventilation using a computerized decision support tool that will recommend changes to ventilator settings approximately every 4 hr (with or without a new blood gas). If the patient is spontaneously breathing, it will incorporate real-time measures of effort of breathing (esophageal manometry) to keep it in a target range.
Intervention: Computerized Ventilator Protocol (Other)
REDvent-acute
Acute Phase: The acute phase is defined as the time from intubation until the patient meets weaning criteria, passes the initial oxygenation test (decrease PEEP to 5 cmH2O and FiO2 to 0.5, maintains SpO2 > 90%), and undergoes a Spontaneous Breathing Trial (SBT). Patients will be managed with pressure control plus pressure support ventilation using a computerized decision support tool that will recommend changes to ventilator settings approximately every 4 hr (with or without a new blood gas). If the patient is spontaneously breathing, it will incorporate real-time measures of effort of breathing (esophageal manometry) to keep it in a target range.
Intervention: Esophageal Manometry (Diagnostic Test)
REDvent-acute
Acute Phase: The acute phase is defined as the time from intubation until the patient meets weaning criteria, passes the initial oxygenation test (decrease PEEP to 5 cmH2O and FiO2 to 0.5, maintains SpO2 > 90%), and undergoes a Spontaneous Breathing Trial (SBT). Patients will be managed with pressure control plus pressure support ventilation using a computerized decision support tool that will recommend changes to ventilator settings approximately every 4 hr (with or without a new blood gas). If the patient is spontaneously breathing, it will incorporate real-time measures of effort of breathing (esophageal manometry) to keep it in a target range.
Intervention: Respiratory Inductance Plethysmography (RIP) (Diagnostic Test)
REDvent-acute
Acute Phase: The acute phase is defined as the time from intubation until the patient meets weaning criteria, passes the initial oxygenation test (decrease PEEP to 5 cmH2O and FiO2 to 0.5, maintains SpO2 > 90%), and undergoes a Spontaneous Breathing Trial (SBT). Patients will be managed with pressure control plus pressure support ventilation using a computerized decision support tool that will recommend changes to ventilator settings approximately every 4 hr (with or without a new blood gas). If the patient is spontaneously breathing, it will incorporate real-time measures of effort of breathing (esophageal manometry) to keep it in a target range.
Intervention: Diaphragm Ultrasound (Diagnostic Test)
REDvent-acute
Acute Phase: The acute phase is defined as the time from intubation until the patient meets weaning criteria, passes the initial oxygenation test (decrease PEEP to 5 cmH2O and FiO2 to 0.5, maintains SpO2 > 90%), and undergoes a Spontaneous Breathing Trial (SBT). Patients will be managed with pressure control plus pressure support ventilation using a computerized decision support tool that will recommend changes to ventilator settings approximately every 4 hr (with or without a new blood gas). If the patient is spontaneously breathing, it will incorporate real-time measures of effort of breathing (esophageal manometry) to keep it in a target range.
Intervention: Maximal Inspiratory Pressure (Diagnostic Test)
Control-acute
Acute Phase: The acute phase is defined as the time from intubation until the patient meets weaning criteria, passes the initial oxygenation test (decrease PEEP to 5 cmH2O and FiO2 to 0.5, maintains SpO2 > 90%), and undergoes a Spontaneous Breathing Trial (SBT). Ventilator management will be per usual care until the patient meets weaning criteria and passes the oxygenation test.
Intervention: Esophageal Manometry (Diagnostic Test)
Control-acute
Acute Phase: The acute phase is defined as the time from intubation until the patient meets weaning criteria, passes the initial oxygenation test (decrease PEEP to 5 cmH2O and FiO2 to 0.5, maintains SpO2 > 90%), and undergoes a Spontaneous Breathing Trial (SBT). Ventilator management will be per usual care until the patient meets weaning criteria and passes the oxygenation test.
Intervention: Respiratory Inductance Plethysmography (RIP) (Diagnostic Test)
Control-acute
Acute Phase: The acute phase is defined as the time from intubation until the patient meets weaning criteria, passes the initial oxygenation test (decrease PEEP to 5 cmH2O and FiO2 to 0.5, maintains SpO2 > 90%), and undergoes a Spontaneous Breathing Trial (SBT). Ventilator management will be per usual care until the patient meets weaning criteria and passes the oxygenation test.
Intervention: Diaphragm Ultrasound (Diagnostic Test)
Control-acute
Acute Phase: The acute phase is defined as the time from intubation until the patient meets weaning criteria, passes the initial oxygenation test (decrease PEEP to 5 cmH2O and FiO2 to 0.5, maintains SpO2 > 90%), and undergoes a Spontaneous Breathing Trial (SBT). Ventilator management will be per usual care until the patient meets weaning criteria and passes the oxygenation test.
Intervention: Maximal Inspiratory Pressure (Diagnostic Test)
REDvent-weaning
Weaning Phase: The weaning phase is defined as the time from the first Spontaneous Breathing Trial (SBT) until the patient successfully passes an SBT or is extubated (whichever comes first). Patients who pass the initial SBT at the end of the acute phase will not undergo weaning phase randomization. Patients will be managed in a pressure support/CPAP mode of ventilation with assessments or changes to the level of pressure support every 4 hours, targeting maintaining effort of breathing (esophageal manometry) in a normal range. An SBT will be conducted daily, and the weaning phase will continue until the patient passes the SBT.
Intervention: Computerized Ventilator Protocol (Other)
REDvent-weaning
Weaning Phase: The weaning phase is defined as the time from the first Spontaneous Breathing Trial (SBT) until the patient successfully passes an SBT or is extubated (whichever comes first). Patients who pass the initial SBT at the end of the acute phase will not undergo weaning phase randomization. Patients will be managed in a pressure support/CPAP mode of ventilation with assessments or changes to the level of pressure support every 4 hours, targeting maintaining effort of breathing (esophageal manometry) in a normal range. An SBT will be conducted daily, and the weaning phase will continue until the patient passes the SBT.
Intervention: Esophageal Manometry (Diagnostic Test)
REDvent-weaning
Weaning Phase: The weaning phase is defined as the time from the first Spontaneous Breathing Trial (SBT) until the patient successfully passes an SBT or is extubated (whichever comes first). Patients who pass the initial SBT at the end of the acute phase will not undergo weaning phase randomization. Patients will be managed in a pressure support/CPAP mode of ventilation with assessments or changes to the level of pressure support every 4 hours, targeting maintaining effort of breathing (esophageal manometry) in a normal range. An SBT will be conducted daily, and the weaning phase will continue until the patient passes the SBT.
Intervention: Respiratory Inductance Plethysmography (RIP) (Diagnostic Test)
REDvent-weaning
Weaning Phase: The weaning phase is defined as the time from the first Spontaneous Breathing Trial (SBT) until the patient successfully passes an SBT or is extubated (whichever comes first). Patients who pass the initial SBT at the end of the acute phase will not undergo weaning phase randomization. Patients will be managed in a pressure support/CPAP mode of ventilation with assessments or changes to the level of pressure support every 4 hours, targeting maintaining effort of breathing (esophageal manometry) in a normal range. An SBT will be conducted daily, and the weaning phase will continue until the patient passes the SBT.
Intervention: Diaphragm Ultrasound (Diagnostic Test)
REDvent-weaning
Weaning Phase: The weaning phase is defined as the time from the first Spontaneous Breathing Trial (SBT) until the patient successfully passes an SBT or is extubated (whichever comes first). Patients who pass the initial SBT at the end of the acute phase will not undergo weaning phase randomization. Patients will be managed in a pressure support/CPAP mode of ventilation with assessments or changes to the level of pressure support every 4 hours, targeting maintaining effort of breathing (esophageal manometry) in a normal range. An SBT will be conducted daily, and the weaning phase will continue until the patient passes the SBT.
Intervention: Maximal Inspiratory Pressure (Diagnostic Test)
Control-weaning
Weaning Phase: The weaning phase is defined as the time from the first Spontaneous Breathing Trial (SBT) until the patient successfully passes an SBT or is extubated (whichever comes first). Patients who pass the initial SBT at the end of the acute phase will not undergo weaning phase randomization. Ventilator management will be per usual care. An SBT will be conducted daily, and the weaning phase will continue until the patient passes the SBT.
Intervention: Esophageal Manometry (Diagnostic Test)
Control-weaning
Weaning Phase: The weaning phase is defined as the time from the first Spontaneous Breathing Trial (SBT) until the patient successfully passes an SBT or is extubated (whichever comes first). Patients who pass the initial SBT at the end of the acute phase will not undergo weaning phase randomization. Ventilator management will be per usual care. An SBT will be conducted daily, and the weaning phase will continue until the patient passes the SBT.
Intervention: Respiratory Inductance Plethysmography (RIP) (Diagnostic Test)
Control-weaning
Weaning Phase: The weaning phase is defined as the time from the first Spontaneous Breathing Trial (SBT) until the patient successfully passes an SBT or is extubated (whichever comes first). Patients who pass the initial SBT at the end of the acute phase will not undergo weaning phase randomization. Ventilator management will be per usual care. An SBT will be conducted daily, and the weaning phase will continue until the patient passes the SBT.
Intervention: Diaphragm Ultrasound (Diagnostic Test)
Control-weaning
Weaning Phase: The weaning phase is defined as the time from the first Spontaneous Breathing Trial (SBT) until the patient successfully passes an SBT or is extubated (whichever comes first). Patients who pass the initial SBT at the end of the acute phase will not undergo weaning phase randomization. Ventilator management will be per usual care. An SBT will be conducted daily, and the weaning phase will continue until the patient passes the SBT.
Intervention: Maximal Inspiratory Pressure (Diagnostic Test)
Outcomes
Primary Outcomes
Median Duration of Weaning
Time Frame: First 28 days of Mechanical Ventilation
Time from first attempted SBT until SBT passage or extubation \[whichever comes first\]
Secondary Outcomes
- 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)
Investigators
Robinder Khemani
Principal Investigator
Children's Hospital Los Angeles