Summary

for people ages up to 18 years (full criteria)
at San Francisco, California and other locations
study started
estimated completion

Description

Summary

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).

Details

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.

Keywords

Acute Respiratory Distress Syndrome in Children Pediatric Acute Respiratory Distress Syndrome (PARDS) Acute Respiratory Distress Syndrome (ARDS) acute respiratory failure child pediatric intensive care unit Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome Either supine or prone positioning and either CMV or HFOV Supine / CMV Prone / CMV Supine / HVOF Prone / HFOV

Eligibility

You can join if…

Open to people ages up to 18 years

Intubated and mechanically ventilated with severe PARDS for <48 hours per PALICC guidelines (chest imaging consistent with acute pulmonary parenchymal disease and OI ≥16 or OSI ≥12.3). We require two blood gases meeting 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).

You CAN'T join if...

  • 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., bronchiolitis 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
  • Post lung transplant
  • Home ventilator (including noninvasive) or home oxygen dependent
  • 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)
  • Received either prone positioning or any high-frequency mode of mechanical ventilation with current illness
  • 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

Locations

  • UCSF Benioff Children's accepting new patients
    San Francisco California 94143 United States
  • UC Davis Medical Center accepting new patients
    Sacramento California 95817 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of Pennsylvania
Links
Study Website
ID
NCT03896763
Study Type
Interventional
Last Updated