Purpose

Severe pediatric acute respiratory distress syndrome (PARDS) is a life-threatening and frequent problem experienced by thousands of children each year. Little evidence supports current supportive practices during their critical illness. The overall objective of this study is to identify the best positional and/or ventilation practice that leads to improved patient outcomes in these critically ill children. We hypothesize that children with severe PARDS treated with either prone positioning or high-frequency oscillatory ventilation (HFOV) will demonstrate more days off the ventilator when compared to children treated with supine positioning or conventional mechanical ventilation (CMV).

Condition

Eligibility

Eligible Ages
Under 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

Intubated and mechanically ventilated with moderate-severe PARDS for <48 hours per PALICC guidelines (chest imaging consistent with acute pulmonary parenchymal disease and OI ≥12 or OSI ≥10). We require two blood gases meeting moderate-severe PARDS criteria (separated by at least 4 ± 2 hours during which time the clinical team is actively working to recruit lung volume and optimize the patient's hemodynamic status per PALICC guidelines; specifically, incremental and decremental PEEP changes to optimize lung volume). A second blood gas is not required for OI ≥16.

Exclusion Criteria

  • Perinatal related lung disease
  • Congenital diaphragmatic hernia or congenital/acquired diaphragm paralysis
  • Respiratory failure explained by cardiac failure or fluid overload
  • Cyanotic heart disease
  • Cardiomyopathy
  • Unilateral lung disease
  • Primary pulmonary hypertension
  • Intubated for status asthmaticus
  • Obstructive airway disease (e.g., Severe airways disease without parenchymal involvement or disease characterized by hypercapnia with FiO2 <0.30 and/or evidence of increased resistance visible on the flow - time scalar and/or presence of intrinsic PEEP)
  • Active air leak
  • Bronchiolitis obliterans
  • Post hematopoietic stem cell transplant; specifically, patients receiving continuous supplemental oxygen for three or more days prior to intubation; receiving noninvasive ventilation for more than 24 hours prior to intubation; receiving more than one vasoactive medication at time of meeting inclusion criteria; spending more than four days in the PICU prior to intubation; supported on or with immediate plans for renal replacement therapies; with two or more allogeneic transplants; who relapsed after the transplant; or with diffuse alveolar hemorrhage
  • Post lung transplant
  • Home ventilator (including noninvasive) or home oxygen dependent (exception: night-time noninvasive ventilation (CPAP/BiPAP) or oxygen for obstructive sleep apnea is permitted)
  • Neuromuscular respiratory failure
  • Critical airway (e.g., post laryngotracheal surgery or new tracheostomy) or anatomical obstruction of the lower airway (e.g., mediastinal mass)
  • Facial surgery or trauma in previous 2 weeks
  • Head trauma (managed with hyperventilation)
  • Intracranial bleeding
  • Unstable spine, femur or pelvic fractures
  • Acute abdominal process/open abdomen
  • Morbid obesity (2w-24 months: WHO weight-for-length/height z-score ≥+3; ≥2 years: WHO body mass index (BMI)-for-age z-score ≥+3)
  • Currently receiving either prone positioning or any high-frequency mode of MV with current illness (Up to 4 hours of prone positioning and/or any mode of high-frequency mode of MV is allowed as long as the therapies are off for least 4 hours prior to the subject meeting oxygenation criteria.)
  • Supported on ECMO during the current admission
  • Family/medical team not providing full support (patient treatment considered futile)
  • Previously enrolled in current study
  • Enrolled in any other interventional clinical trial not approved for co-enrollment
  • Known pregnancy

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Factorial Assignment
Intervention Model Description
Two-by-two factorial, response-adaptive, randomized controlled clinical trial
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Supine / CMV
Supine positioning and conventional mechanical ventilation
  • Other: Either supine or prone positioning and either CMV or HFOV
    Supine positioning: Subjects randomized to supine positioning will remain supine. Prone positioning: Subjects randomized to prone positioning will be positioned prone ≥16 hours/day for a maximum of 28 days. CMV strategy: Low tidal volume to obtain exhaled Vt of 5-7 ml/kg (ideal body weight), PIP goal limited to ≤ 28 cm H2O and lung recruitment maneuver to identify best PEEP then maintained per PEEP-FiO2 grid. HFOV strategy: Frequency at 8-12 Hz, amplitude (delta-P) 60-90 and mPaw recruitment maneuver.
    Other names:
    • Supine positioning
    • Prone positioing
    • Conventional mechanical ventilation (CMV)
    • High frequency oscillatory ventilation (HFOV)
Experimental
Prone / CMV
Prone positioning and conventional mechanical ventilation
  • Other: Either supine or prone positioning and either CMV or HFOV
    Supine positioning: Subjects randomized to supine positioning will remain supine. Prone positioning: Subjects randomized to prone positioning will be positioned prone ≥16 hours/day for a maximum of 28 days. CMV strategy: Low tidal volume to obtain exhaled Vt of 5-7 ml/kg (ideal body weight), PIP goal limited to ≤ 28 cm H2O and lung recruitment maneuver to identify best PEEP then maintained per PEEP-FiO2 grid. HFOV strategy: Frequency at 8-12 Hz, amplitude (delta-P) 60-90 and mPaw recruitment maneuver.
    Other names:
    • Supine positioning
    • Prone positioing
    • Conventional mechanical ventilation (CMV)
    • High frequency oscillatory ventilation (HFOV)
Experimental
Supine / HVOF
Supine positioning and high-frequency oscillatory ventilation
  • Other: Either supine or prone positioning and either CMV or HFOV
    Supine positioning: Subjects randomized to supine positioning will remain supine. Prone positioning: Subjects randomized to prone positioning will be positioned prone ≥16 hours/day for a maximum of 28 days. CMV strategy: Low tidal volume to obtain exhaled Vt of 5-7 ml/kg (ideal body weight), PIP goal limited to ≤ 28 cm H2O and lung recruitment maneuver to identify best PEEP then maintained per PEEP-FiO2 grid. HFOV strategy: Frequency at 8-12 Hz, amplitude (delta-P) 60-90 and mPaw recruitment maneuver.
    Other names:
    • Supine positioning
    • Prone positioing
    • Conventional mechanical ventilation (CMV)
    • High frequency oscillatory ventilation (HFOV)
Experimental
Prone / HFOV
Prone positioning and high-frequency oscillatory ventilation
  • Other: Either supine or prone positioning and either CMV or HFOV
    Supine positioning: Subjects randomized to supine positioning will remain supine. Prone positioning: Subjects randomized to prone positioning will be positioned prone ≥16 hours/day for a maximum of 28 days. CMV strategy: Low tidal volume to obtain exhaled Vt of 5-7 ml/kg (ideal body weight), PIP goal limited to ≤ 28 cm H2O and lung recruitment maneuver to identify best PEEP then maintained per PEEP-FiO2 grid. HFOV strategy: Frequency at 8-12 Hz, amplitude (delta-P) 60-90 and mPaw recruitment maneuver.
    Other names:
    • Supine positioning
    • Prone positioing
    • Conventional mechanical ventilation (CMV)
    • High frequency oscillatory ventilation (HFOV)

Recruiting Locations

University of Maryland Medical Center-Children's Hospital
Baltimore, Maryland 21201
Contact:
Ana Lia Graciano, MD
agraciano@som.umaryland.edu

More Details

Status
Recruiting
Sponsor
University of Pennsylvania

Study Contact

Amy Cassidy
215-898-4151
acassidy@nursing.upenn.edu

Detailed Description

PROSpect is a two-by-two factorial, response-adaptive, randomized controlled clinical trial of supine/prone positioning and conventional mechanical ventilation (CMV)/high-frequency oscillatory ventilation (HFOV). About 45 pediatric intensive care units (PICUs), 30 U.S. and 15 international, with at least 5 years of experience with prone positioning and HFOV in the care of pediatric patients with severe Pediatric Acute Respiratory Distress Syndrome (PARDS), that can provide back-up extracorporeal membrane oxygenation (ECMO) support, are participating. Eligible consecutive subjects with severe PARDS will be randomized to one of four groups: supine/CMV, prone/CMV, supine/HFOV, prone/HFOV. Subjects who fail their assigned positional and/or ventilation therapy for either persistent hypoxia or hypercapnia may receive the reciprocal therapy while being considered for ECMO cannulation. Our primary outcome is ventilator-free days (VFD) through day 28, where non-survivors receive zero VFD. We hypothesize that children with severe PARDS treated with either prone positioning or HFOV will demonstrate ≥ 2 more VFD. Our secondary outcome is nonpulmonary organ failure-free days. We will also explore the interaction effects of prone positioning with HFOV on VFDs and also investigate the impact of these interventions on 90-day in-hospital mortality and, among survivors, the duration of mechanical ventilation, PICU and hospital length of stay, and the trajectory of post-PICU functional status and health-related quality of life (HRQL). Up to 1000 subjects with severe PARDS will be randomized, stratified by age group and direct/indirect lung injury. Adaptive randomization will first occur after 400 patients are randomized and have been followed for 28 days, and every 100 patients thereafter. At these randomization update analyses, new allocation probabilities will be computed based on ongoing intention-to-treat trial results, increasing allocation to well performing arms and decreasing allocation to poorly performing arms. Data will be analyzed per intention-to-treat for the primary analyses and per-protocol received for primary, secondary and exploratory analyses.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.