Clinical trial NCT03709199: Long Term Follow up of Children Enrolled in the REDvent Study
Official title: The Effect of Intensive Care Unit Therapies and Mechanical Ventilation Strategy on Long Term Outcome in Pediatric ARDS A Follow-up of the Real-time Effort Driven VENTilator Management Study (REDvent)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Respiratory Distress Syndrome, Adult
Ventilator-Induced Lung Injury
Neurocognitive Dysfunction
Quality of Life
Respiration Disorders
Lead sponsor: Children's Hospital Los Angeles
Sponsor class: OTHER
First posted: 2018-10-17
Enrollment: 176
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is a long term follow-up of children already enrolled in the RED-vent study.

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.


Eligibility criteria: Inclusion Criteria:

1. Children \> 1 month (at least 44 weeks Corrected Gestational Age) and ≤ 18 years of age AND
2. 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
3. Who are within 48 hours of initiation of invasive mechanical ventilation (allow for up to 72 hours for those transferred from another institution) AND
4. Enrolled in the REDvent Study

Exclusion Criteria (1-5 are REDvent exclusion):

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 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
5. Primary Attending physician refuses (will be cleared with primary attending before approaching the patient) OR
6. Death in the ICU OR
7. New DNR orders during acute illness in ICU OR
8. Primary Language not English or Spanish OR
9. Children in foster care or a ward of the state.

Primary outcomes:
measure: Ventilation In-homogeneity using lung clearance index with nitrogen washout
timeFrame: 6 months after ICU discharge
measure: Neurocognitive function using a standardized score derived from Batelle-2 or WISC-5 cognitive tests
timeFrame: 3 months after ICU discharge
measure: Health Related Quality of Life as measured by PedsQL generic core scale
timeFrame: 3 months after ICU discharge
measure: Functional Status as measured by the pediatric functional status scale
timeFrame: 3 months after ICU discharge
Secondary outcomes:
measure: Functional Residual Capacity (Lung volume at end-expiration).
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Functional Residual Capacity (Lung volume at end-expiration).
timeFrame: 6 months after ICU discharge
measure: Phase Angle (a measure of thoraco-abdominal asynchrony and abnormal respiratory mechanics)
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Phase Angle (a measure of thoraco-abdominal asynchrony and abnormal respiratory mechanics)
timeFrame: 6 Months after ICU Discharge
measure: Diaphragm Thickness on exhalation
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Diaphragm Thickness on exhalation
timeFrame: 6 months after ICU discharge
measure: Diaphragm Thickness on inspiration
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Diaphragm Thickness on inspiration
timeFrame: 6 months after ICU discharge
measure: Diaphragm Thickening fraction (measure of contractile activity)
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Diaphragm Thickening fraction (measure of contractile activity)
timeFrame: 6 months after ICU discharge
measure: Ventilation In-homogeneity using lung clearance index with nitrogen washout
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Forced Expiratory Volume in 1 second (FEV1)
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Forced Expiratory Volume in 1 second (FEV1)
timeFrame: 6 months after ICU discharge
measure: Forced Vital Capacity (FVC)
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Forced Vital Capacity (FVC)
timeFrame: 6 months after ICU discharge
measure: Forced expiratory flow at 25-75% (FEF 25-75)
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Forced expiratory flow at 25-75% (FEF 25-75)
timeFrame: 6 months post ICU discharge
measure: VT - tidal volume from spirometry during tidal breathing
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: VT - tidal volume from spirometry during tidal breathing
timeFrame: 6 months after ICU discharge
measure: Total Lung Capacity- TLC measured during spirometry
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Total Lung Capacity- TLC measured during spirometry
timeFrame: 6 months after ICU discharge
measure: Forced vital capacity- measured during spirometry
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Forced vital capacity- measured during spirometry
timeFrame: 6 months after ICU discharge
measure: Respiratory Muscle Strength Maximum inspiratory pressure (MIP)
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Respiratory Muscle Strength Maximum inspiratory pressure (MIP)
timeFrame: 6 months after ICU discharge
measure: Respiratory Muscle Strength Maximum expiratory pressure (MEP)
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: Respiratory Muscle Strength Maximum expiratory pressure (MEP)
timeFrame: 6 months after ICU discharge
measure: Neurocognitive function using a standardized score derived from Batelle-2 or WISC-5 cognitive tests
timeFrame: 12 months after ICU discharge
measure: Health Related Quality of Life as measured by PedsQL generic core scale
timeFrame: ICU discharge
measure: Health Related Quality of Life as measured by PedsQL generic core scale
timeFrame: 1 month after ICU discharge
measure: Health Related Quality of Life as measured by PedsQL generic core scale
timeFrame: 2 months after ICU discharge
measure: Health Related Quality of Life as measured by PedsQL generic core scale
timeFrame: 6 months after ICU discharge
measure: Health Related Quality of Life as measured by PedsQL generic core scale
timeFrame: 12 months after ICU discharge
measure: Functional Status as measured by the pediatric functional status scale
timeFrame: ICU discharge
measure: Functional Status as measured by the pediatric functional status scale
timeFrame: 1 month after ICU discharge
measure: Functional Status as measured by the pediatric functional status scale
timeFrame: 2 months after ICU discharge
measure: Functional Status as measured by the pediatric functional status scale
timeFrame: 6 months after ICU discharge
measure: Functional Status as measured by the pediatric functional status scale
timeFrame: 12 months after ICU discharge
measure: Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.
timeFrame: ICU discharge
measure: Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.
timeFrame: 1 month after ICU discharge
measure: Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.
timeFrame: 2 months after ICU discharge
measure: Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.
timeFrame: 3 months after ICU discharge
measure: Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.
timeFrame: 6 months after ICU discharge
measure: Respiratory Status - questionnaire detailing respiratory medications and therapies as well as healthcare utilization.
timeFrame: 12 months after ICU discharge
measure: Emotional Health Outcomes using the (BASC-3) to assess emotional and behavioral abnormalities and UCLA Reaction Index to assess post traumatic stress
timeFrame: 3 months after ICU discharge
measure: Emotional Health Outcomes using the (BASC-3) to assess emotional and behavioral abnormalities and UCLA Reaction Index to assess post traumatic stress
timeFrame: 12 months after ICU discharge
Other outcomes:
measure: 6 minute walk test
timeFrame: Prior to Hospital Discharge and no more than 1 month after ICU discharge
measure: 6 minute walk test
timeFrame: 6 months after ICU discharge
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
Study officials:
affiliation: Children's Hospital Los Angeles
name: Robinder Khemani, MD
role: PRINCIPAL_INVESTIGATOR
References: