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Real-time Effort Driven VENTilator Management (REDvent)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03266016
Recruitment Status : Recruiting
First Posted : August 29, 2017
Last Update Posted : August 21, 2020
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Children's Hospital of Philadelphia
Information provided by (Responsible Party):
Children's Hospital Los Angeles

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.

Condition or disease Intervention/treatment Phase
Ventilation Therapy; Complications Diaphragm Disease Pediatric Respiratory Diseases Other: Computerized Ventilator Protocol Diagnostic Test: Esophageal Manometry Diagnostic Test: Respiratory Inductance Plethysmography (RIP) Diagnostic Test: Diaphragm Ultrasound Diagnostic Test: Maximal Inspiratory Pressure Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 276 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized Controlled Trial
Masking: Single (Outcomes Assessor)
Masking Description: Analysis Blinded
Primary Purpose: Prevention
Official Title: Identifying and Preventing Ventilator Induced Diaphragm Dysfunction in Children
Actual Study Start Date : October 21, 2017
Estimated Primary Completion Date : May 31, 2023
Estimated Study Completion Date : June 30, 2023

Arm Intervention/treatment
Experimental: 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.
Other: Computerized Ventilator Protocol
Computerized Decision Support System which recommends changes to ventilator settings to promote physiologic levels of patient effort of breathing.

Diagnostic Test: Esophageal Manometry
Esophageal Manometry Catheter to measure effort of breathing an transpulmonary pressure

Diagnostic Test: Respiratory Inductance Plethysmography (RIP)
RIP bands to measure thoraco-abdominal synchrony during spontaneous breathing trials

Diagnostic Test: Diaphragm Ultrasound
Daily measurement of diaphragm thickness and diaphragm contractile activity

Diagnostic Test: Maximal Inspiratory Pressure
Prior to Spontaneous breathing trials, measurement of airway and esophageal maximal inspiratory pressure during airway occlusion

Placebo Comparator: 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.
Diagnostic Test: Esophageal Manometry
Esophageal Manometry Catheter to measure effort of breathing an transpulmonary pressure

Diagnostic Test: Respiratory Inductance Plethysmography (RIP)
RIP bands to measure thoraco-abdominal synchrony during spontaneous breathing trials

Diagnostic Test: Diaphragm Ultrasound
Daily measurement of diaphragm thickness and diaphragm contractile activity

Diagnostic Test: Maximal Inspiratory Pressure
Prior to Spontaneous breathing trials, measurement of airway and esophageal maximal inspiratory pressure during airway occlusion

Experimental: 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.
Other: Computerized Ventilator Protocol
Computerized Decision Support System which recommends changes to ventilator settings to promote physiologic levels of patient effort of breathing.

Diagnostic Test: Esophageal Manometry
Esophageal Manometry Catheter to measure effort of breathing an transpulmonary pressure

Diagnostic Test: Respiratory Inductance Plethysmography (RIP)
RIP bands to measure thoraco-abdominal synchrony during spontaneous breathing trials

Diagnostic Test: Diaphragm Ultrasound
Daily measurement of diaphragm thickness and diaphragm contractile activity

Diagnostic Test: Maximal Inspiratory Pressure
Prior to Spontaneous breathing trials, measurement of airway and esophageal maximal inspiratory pressure during airway occlusion

Placebo Comparator: 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.
Diagnostic Test: Esophageal Manometry
Esophageal Manometry Catheter to measure effort of breathing an transpulmonary pressure

Diagnostic Test: Respiratory Inductance Plethysmography (RIP)
RIP bands to measure thoraco-abdominal synchrony during spontaneous breathing trials

Diagnostic Test: Diaphragm Ultrasound
Daily measurement of diaphragm thickness and diaphragm contractile activity

Diagnostic Test: Maximal Inspiratory Pressure
Prior to Spontaneous breathing trials, measurement of airway and esophageal maximal inspiratory pressure during airway occlusion




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Ventilator Free Days [ Time Frame: 28 and 60 days ]
    Days alive and not on mechanical ventilation

  2. Extubation Failure [ Time Frame: 7 days after extubation ]
    re-intubation or use of non invasive ventilation

  3. Mortality [ Time Frame: Through study completion up to maximum of 90 Days ]
    Death

  4. Maximal Inspiratory Airway Pressure During Airway Occlusion (aPiMax) [ Time Frame: Each day after passing oxygenation test through extubation up to a maximum of 28 days ]
    Measured during standardized airway occlusion maneuvers

  5. Maximal Inspiratory Esophageal Pressure During Airway Occlusion (ePiMax) [ Time Frame: Each day after passing oxygenation test through extubation up to a maximum of 28 days ]
    Measured during standardized airway occlusion maneuvers

  6. Change in diaphragm thickness on Exhalation (Dte) [ Time Frame: Each day from study initiation until extubation up to a maximum of 28 days ]
    From daily ultrasound measurement



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Children > 1 month (>44 weeks CGA) and ≤ 18 years of age AND
  2. 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
  3. 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:

  1. Contraindications to use of an esophageal catheter (i.e. severe mucosal bleeding, nasal encephalocele, transphenoidal surgery) OR
  2. Contraindications to use of RIP bands (i.e. omphalocele, chest immobilizer or cast) OR
  3. Conditions precluding diaphragm ultrasound measurement (i.e. abdominal wall defects, pregnancy) OR
  4. 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
  5. Primary Attending physician refuses (will be cleared with primary attending before approaching the patient).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03266016


Contacts
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Contact: Robinder G Khemani, MD,MsCI 3233612557 rkhemani@chla.usc.edu

Locations
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United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Sponsors and Collaborators
Children's Hospital Los Angeles
National Heart, Lung, and Blood Institute (NHLBI)
Children's Hospital of Philadelphia
Investigators
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Principal Investigator: Robinder G Khemani, MD, MsCI Children's Hospital Los Angeles
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Children's Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT03266016    
Other Study ID Numbers: CHLA-17-00235
First Posted: August 29, 2017    Key Record Dates
Last Update Posted: August 21, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: De-Identified IPD will be made available as per NIH guidelines.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiration Disorders
Respiratory Tract Diseases