Real-time Effort Driven VENTilator Management

NCT03266016 | Completed Results DMC

• 2 other identifiers: CHLA-17-002355R01HL134666-05
• Study Type: interventional
• Target: 248
• Locations: 1 country
• Sites: 1

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.

Conditions

Ventilation Therapy; Complications; Diaphragm Disease; Pediatric Respiratory Diseases

Outcome Measures

Primary Outcomes (1)

• Median Duration of Weaning

  Time from first attempted SBT until SBT passage or extubation \[whichever comes first\]

  First 28 days of Mechanical Ventilation

Secondary Outcomes (6)

• 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

Study Arms (4)

REDvent-acute

EXPERIMENTAL

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; Diagnostic Test: Esophageal Manometry; Diagnostic Test: Respiratory Inductance Plethysmography (RIP); Diagnostic Test: Diaphragm Ultrasound; Diagnostic Test: Maximal Inspiratory Pressure

Control-acute

PLACEBO COMPARATOR

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; Diagnostic Test: Respiratory Inductance Plethysmography (RIP); Diagnostic Test: Diaphragm Ultrasound; Diagnostic Test: Maximal Inspiratory Pressure

REDvent-weaning

EXPERIMENTAL

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; Diagnostic Test: Esophageal Manometry; Diagnostic Test: Respiratory Inductance Plethysmography (RIP); Diagnostic Test: Diaphragm Ultrasound; Diagnostic Test: Maximal Inspiratory Pressure

Control-weaning

PLACEBO COMPARATOR

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; Diagnostic Test: Respiratory Inductance Plethysmography (RIP); Diagnostic Test: Diaphragm Ultrasound; Diagnostic Test: Maximal Inspiratory Pressure

Interventions

Computerized Ventilator Protocol OTHER

Computerized Decision Support System which recommends changes to ventilator settings to promote physiologic levels of patient effort of breathing.

REDvent-acute; REDvent-weaning

Esophageal Manometry DIAGNOSTIC_TEST

Esophageal Manometry Catheter to measure effort of breathing an transpulmonary pressure

Control-acute; Control-weaning; REDvent-acute; REDvent-weaning

Respiratory Inductance Plethysmography (RIP) DIAGNOSTIC_TEST

RIP bands to measure thoraco-abdominal synchrony during spontaneous breathing trials

Control-acute; Control-weaning; REDvent-acute; REDvent-weaning

Diaphragm Ultrasound DIAGNOSTIC_TEST

Daily measurement of diaphragm thickness and diaphragm contractile activity

Control-acute; Control-weaning; REDvent-acute; REDvent-weaning

Maximal Inspiratory Pressure DIAGNOSTIC_TEST

Prior to Spontaneous breathing trials, measurement of airway and esophageal maximal inspiratory pressure during airway occlusion

Control-acute; Control-weaning; REDvent-acute; REDvent-weaning

Eligibility Criteria

• Age: 30 Days - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Children's Hospital of Philadelphia: collaborator

Study Sites (1)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Related Publications (7)

• Khemani RG, Bhalla A, Hotz JC, Klein MJ, Kwok J, Kohler K, Bornstein D, Chang D, Armenta-Quiroz A, Vu K, Smith E, Suresh A, Baron D, Bonilla-Cartagena J, Ross PA, Deakers T, Beltramo F, Nelson L, Shah S, Elkunovich M, Curley MAQ, Mack W, Newth CJL. Randomized Trial of Lung and Diaphragm Protective Ventilation in Children. NEJM Evid. 2025 Jun;4(6):EVIDoa2400360. doi: 10.1056/EVIDoa2400360. Epub 2025 May 27.

  PMID: 40423397 DERIVED

• Vedrenne-Cloquet M, Ito Y, Hotz J, Klein MJ, Herrera M, Chang D, Bhalla AK, Newth CJL, Khemani RG. Phenotypes based on respiratory drive and effort to identify the risk factors when P0.1 fails to estimate ∆PES in ventilated children. Crit Care. 2024 Oct 4;28(1):325. doi: 10.1186/s13054-024-05103-x.

  PMID: 39367452 DERIVED

• Ito Y, Herrera MG, Hotz JC, Kyogoku M, Newth CJL, Bhalla AK, Takeuchi M, Khemani RG. Estimation of inspiratory effort using airway occlusion maneuvers in ventilated children: a secondary analysis of an ongoing randomized trial testing a lung and diaphragm protective ventilation strategy. Crit Care. 2023 Nov 29;27(1):466. doi: 10.1186/s13054-023-04754-6.

  PMID: 38031116 DERIVED

• Knox KE, Hotz JC, Newth CJL, Khoo MCK, Khemani RG. A 30-Minute Spontaneous Breathing Trial Misses Many Children Who Go On to Fail a 120-Minute Spontaneous Breathing Trial. Chest. 2023 Jan;163(1):115-127. doi: 10.1016/j.chest.2022.08.2212. Epub 2022 Aug 28.

  PMID: 36037984 DERIVED

• van Dijk J, Blokpoel RGT, Abu-Sultaneh S, Newth CJL, Khemani RG, Kneyber MCJ. Clinical Challenges in Pediatric Ventilation Liberation: A Meta-Narrative Review. Pediatr Crit Care Med. 2022 Dec 1;23(12):999-1008. doi: 10.1097/PCC.0000000000003025. Epub 2022 Jul 14.

  PMID: 35830707 DERIVED

• Shimatani T, Yoon B, Kyogoku M, Kyo M, Ohshimo S, Newth CJL, Hotz JC, Shime N, Khemani RG. Frequency and Risk Factors for Reverse Triggering in Pediatric Acute Respiratory Distress Syndrome during Synchronized Intermittent Mandatory Ventilation. Ann Am Thorac Soc. 2021 May;18(5):820-829. doi: 10.1513/AnnalsATS.202008-1072OC.

  PMID: 33326335 DERIVED

• Khemani RG, Hotz JC, Klein MJ, Kwok J, Park C, Lane C, Smith E, Kohler K, Suresh A, Bornstein D, Elkunovich M, Ross PA, Deakers T, Beltramo F, Nelson L, Shah S, Bhalla A, Curley MAQ, Newth CJL. A Phase II randomized controlled trial for lung and diaphragm protective ventilation (Real-time Effort Driven VENTilator management). Contemp Clin Trials. 2020 Jan;88:105893. doi: 10.1016/j.cct.2019.105893. Epub 2019 Nov 16.

  PMID: 31740425 DERIVED

MeSH Terms

Interventions

Maximal Respiratory Pressures

Intervention Hierarchy (Ancestors)

Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis

Limitations and Caveats

The structure of the trial was as described but the analytic approach was not to treat them as 4 different groups. All patients who were exposed to REDVent versus usual care during the acute phase were analyzed for outcomes attributed to the acute phase.

Results Point of Contact

• Title: Dr. Robinder Khemani, MD. Medical Staff/USC Faculty
• Organization: Children's Hospital Los Angeles

rkhemani@chla.usc.edu

3233612376

Study Officials

• Robinder G Khemani, MD, MsCI

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Analysis Blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized Controlled Trial

Study Record Dates

• First Submitted: August 23, 2017
• First Posted: August 29, 2017
• Study Start: October 21, 2017
• Primary Completion: April 1, 2024
• Study Completion: June 20, 2024
• Last Updated: September 17, 2025
• Results First Posted: July 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Within 5 years of publication of primary manuscript
• Access Criteria: Will be made available through biolinc

Locations

US (1)