Long Term Follow up of Children Enrolled in the REDvent Study

NCT03709199 | Active Not Recruiting

• 1 other identifier: CHLA-18-00354
• Study Type: observational
• Target: 176
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective observational follow-up study of children enrolled in a single center randomized controlled trial (REDvent). Nearly 50% of adult Acute Respiratory Distress Syndrome (ARDS) survivors are left with significant abnormalities in pulmonary, physical, neurocognitive function and Health Related Quality of Life (HRQL) which may persist for years.Data in pediatric ARDS (PARDS) survivors is limited. More importantly, there are no data identifying potentially modifiable factors during ICU care which are associated with long term impairments, which may include medication choices, or complications from mechanical ventilator (MV) management in the ICU including ventilator induced lung injury (VILI) or ventilator induced diaphragm dysfunction (VIDD). The Real-time effort driven ventilator (REDvent) trial is testing a ventialtor management algorithm which may prevent VIDD and VILI. VIDD and VILI have strong biologic plausibility to affect the post-ICU health of children with likely sustained effects on lung repair and muscle strength. Moreover, common medication choices (i.e. neuromuscular blockade, corticosteroids) or other complications in the ICU (i.e. delirium) are likely to have independent effects on the long term health of these children. This proposed study will obtain serial follow-up of subjects enrolled in REDvent (intervention and control patients). The central hypothesis is that preventing VIDD, VILI and shortening time on MV will have a measureable impact on longer term function by mitigating abnormalities in pulmonary function (PFTs), neurocognitive function and emotional health, functional status and HRQL after hospital discharge for children with PARDS. For all domains, the investigators will determine the frequency, severity and trajectory of recovery of abnormalities amongst PARDS survivors after ICU discharge, identify risk factors for their development, and determine if they are prevented by REDvent. They will leverage the detailed and study specific respiratory physiology data being obtained in REDvent, and use a variety of multi-variable models for comprehensive analysis. Completion of this study will enable the investigators to identify ICU related therapies associated with poor long term outcome, and determine whether they can be mitigated by REDvent.

Conditions

Respiratory Distress Syndrome, Adult; Ventilator-Induced Lung Injury; Neurocognitive Dysfunction; Quality of Life; Respiration Disorders

Outcome Measures

Primary Outcomes (4)

• Ventilation In-homogeneity using lung clearance index with nitrogen washout

  Measured by lung clearance index during multiple breath nitrogen washout testing reported as percent predicted based on age and height as well as a raw number typically ranging from 5-15.

  6 months after ICU discharge

• Neurocognitive function using a standardized score derived from Batelle-2 or WISC-5 cognitive tests

  Standardized IQ-like score derived from Batelle-2 or WISC-5 cognitive tests based on age. Children \< 6 years will receive the Batelle-2 and children \>=6 will receive the WISC-5. Overall score will be use for analysis with a higher value indicating better cognitive function. The range of "average" cognitive function lies between 90-109. Both tests are scored on the same scale

  3 months after ICU discharge

• Health Related Quality of Life as measured by PedsQL generic core scale

  PedsQL generic core scale, with range from 0-100, with the higher score indicating better health related quality of life

  3 months after ICU discharge

• Functional Status as measured by the pediatric functional status scale

  Functional status scale which is scored from normal (score =1) to very severe dysfunction (score =5) in each of 6 domains. The sum score of all domains will be used for analysis, yielding a minimum possible score of 6 and a maximum possible score of 30. Analysis will focus on a change in FSS from baseline (assessed as functional status 1 month prior to ICU admission). An increase in the FSS from baseline to 3 months will be considered as a decline in functional status.

  3 months after ICU discharge

Secondary Outcomes (46)

• Functional Residual Capacity (Lung volume at end-expiration).

  Prior to Hospital Discharge and no more than 1 month after ICU discharge

• Functional Residual Capacity (Lung volume at end-expiration).

  6 months after ICU discharge

• Phase Angle (a measure of thoraco-abdominal asynchrony and abnormal respiratory mechanics)

  Prior to Hospital Discharge and no more than 1 month after ICU discharge

• Phase Angle (a measure of thoraco-abdominal asynchrony and abnormal respiratory mechanics)

  6 Months after ICU Discharge

• Diaphragm Thickness on exhalation

  Prior to Hospital Discharge and no more than 1 month after ICU discharge

Other Outcomes (2)

• 6 minute walk test

  Prior to Hospital Discharge and no more than 1 month after ICU discharge

• 6 minute walk test

  6 months after ICU discharge

Interventions

Ventilation Inhomogeneity DIAGNOSTIC_TEST

Ventilation inhomogeneity will be measured using the Lung Clearance Index (LCI), derived from multiple breath Nitrogen washout during tidal breathing, measured by a mouthpiece or mask covering nose and mouth.

Also known as: Lung Clearance Index

Diaphragm Ultrasound DIAGNOSTIC_TEST

Diaphragm thickness and contractile activity measured during tidal breathing.

Respiratory Inductance Plethysmography DIAGNOSTIC_TEST

Measure of thoraco-abdominal asynchrony during tidal breathing

Also known as: Phase Angle

Spirometry DIAGNOSTIC_TEST

Measurement of Forced Expiratory Volume (FEV1), Forced Vital Capacity and other lung volumes using standard pulmonary function techniques

Also known as: Pulmonary Function Tests

Functional Residual Capacity DIAGNOSTIC_TEST

Measurement using body box plethysmography of functional residual capacity and other lung volumes using standard pulmonary function techniques

Also known as: Pulmonary Function Tests

MIP/MEP DIAGNOSTIC_TEST

Measurement of maximal inspiratory and expiratory pressures during airway occlusion

6 minute walk test DIAGNOSTIC_TEST

Measurement of cardio-respiratory function and capabilities during treadmill walking for 6 minutes.

Neurocognitive Testing DIAGNOSTIC_TEST

Detailed in person neuro-cognitive testing using standardized inventories using either the Battelle Developmental Inventory, second edition (Battelle-2) (age birth to 5 years 11 months) and the Wechsler Intelligence Scale for Children, fifth edition (WISC-5, for age 6 years to 19 years).

Emotional Health Assessment DIAGNOSTIC_TEST

In person and written assessments of children and parents using the Behavioral Assessment System for Children, third edition (BASC-3) for children ≥ 2 years and the UCLA PTSD Reaction Index (UCLA RI) for children ≥ 8 years.

Health Related Quality of Life DIAGNOSTIC_TEST

Standardized instruments to assess (in person, over the phone, or via mail) health related quality of life in children. Parent and child questionnaires.

Also known as: PEDS-QL

Functional Status DIAGNOSTIC_TEST

Survey of overall functional status, administrated by asking a series of questions to patient and families.

Also known as: Functional Status Scale

Respiratory Status Questionnaire DIAGNOSTIC_TEST

Survey of respiratory health, administrated by asking a series of questions to patient and families.

Eligibility Criteria

• Age: 1 Month - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

This is a long term follow-up of children already enrolled in the RED-vent study.

You may qualify if:

• Children \> 1 month (at least 44 weeks Corrected Gestational Age) and ≤ 18 years of age AND
• Supported on mechanical ventilation for pulmonary parenchymal disease (i.e., pneumonia, bronchiolitis, Pediatric Acute Respiratory Distress Syndrome (PARDS)) with Oxygen Saturation Index (OSI) ≥ 5 or Oxygenation Index (OI) ≥4 115 AND
• Who are within 48 hours of initiation of invasive mechanical ventilation (allow for up to 72 hours for those transferred from another institution) AND
• Enrolled in the REDvent Study

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 precluding conventional methods of weaning (i.e., status asthmaticus, severe lower airway obstruction, critical airway, intracranial hypertension, Extra Corporeal Life Support (ECLS), intubation for UAO, tracheostomy, 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) OR
• Death in the ICU OR
• New DNR orders during acute illness in ICU OR
• Primary Language not English or Spanish OR
• Children in foster care or a ward of the state.

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead

Study Sites (1)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome; Ventilator-Induced Lung Injury; Cognition Disorders; Respiration Disorders

Interventions

Spirometry; Respiratory Function Tests; Functional Residual Capacity; Walk Test

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Lung Injury; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Total Lung Capacity; Lung Volume Measurements; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Exercise Test; Heart Function Tests; Diagnostic Techniques, Cardiovascular

Study Officials

• Robinder Khemani, MD

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: October 17, 2018
• Study Start: October 1, 2018
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: April 17, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)