Clinical trial NCT03896763: PROSpect: Prone and Oscillation Pediatric Clinical Trial
Official title: PROSpect: Prone and Oscillation Pediatric Clinical Trial
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Acute Respiratory Distress Syndrome in Children
Keywords: Pediatric Acute Respiratory Distress Syndrome (PARDS)
Acute Respiratory Distress Syndrome (ARDS)
acute respiratory failure
child
pediatric intensive care unit
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: University Medical Center Groningen
name: Boston Children's Hospital
name: University Hospitals Cleveland Medical Center
First posted: 2019-04-01
Enrollment: 600
Sex: ALL
Minimum age (years): 2
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Two-by-two factorial, response-adaptive, randomized controlled clinical trial
Primary purpose: TREATMENT

Brief 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 high moderate-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).

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 60 pediatric intensive care units (PICUs), two thirds U.S. and one third 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 high moderate-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 600 subjects with severe PARDS will be randomized, stratified by age group and direct/indirect lung injury. Adaptive randomization will first occur after 300 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.

Eligibility criteria: Inclusion criteria:

Intubated and mechanically ventilated with high 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
* Unrepaired 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 dependent with baseline Oxygen Saturation Index (OSI) \>6
* 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
* Open abdomen
* Currently receiving more than 6 consecutive hours of either prone positioning or HFOV
* 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

Primary outcomes:
measure: Ventilator-free Days (VFD)
timeFrame: 28 days
Secondary outcomes:
measure: Nonpulmonary organ failure-free days (OFFD)
timeFrame: 28 days
Other outcomes:
measure: Interaction effects of prone positioning with HFOV on VFDs - number of ventilator-free days
timeFrame: 28 days
measure: 90-day in-hospital mortality
timeFrame: 90 days
measure: Duration of mechanical ventilation (among survivors)
timeFrame: 28 days, 90 days
measure: PICU and hospital length of stay (among survivors)
timeFrame: 90 days
measure: Post PICU discharge functional status
timeFrame: 1, 3, 6, 12 months post PICU discharge
measure: Post PICU discharge health-related quality of life (HRQL)
timeFrame: 1, 3, 6, 12 months post PICU discharge
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Banner Health
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Orange
country: United States
facility: Children's Hospital Orange County
state: California
city: Palo Alto
country: United States
facility: Stanford Children's Health
state: California
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Chicago
country: United States
facility: Ann & Robert Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children at IU Health
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Stead Family Chlldren's Hospital
state: Iowa
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: Baltimore
country: United States
facility: Bloomberg Children's Center, Johns Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: CS Mott Children's Hospital
state: Michigan
city: Omaha
country: United States
facility: Children's Hospital and Medical Center
state: Nebraska
city: Queens
country: United States
facility: Cohen Children's Medical Center
state: New York
city: Durham
country: United States
facility: Duke Children's Hospital
state: North Carolina
city: Cleveland
country: United States
facility: UH Rainbow Babies & Children
state: Ohio
city: Oklahoma City
country: United States
facility: Children's Hospital at Oklahoma University Medical Center
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Children's Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: LeBonheur Children's Hospital
state: Tennessee
city: Dallas
country: United States
facility: Medical City Dallas
state: Texas
city: Dallas
country: United States
facility: Children's Health Dallas
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: Children's Hospital of San Antonio
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Medical Campus
state: Virginia
city: Madison
country: United States
facility: American Family Children's Hospital, University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
city: Perth
country: Australia
facility: Perth Children's Hospital
state: Western Australia
city: Sydney
country: Australia
facility: Children's Hospital at Westmead
city: Sao Paulo
country: Brazil
facility: Sabara Hospital Infantil
city: São Paulo
country: Brazil
facility: Hospital SEPACO
city: Montréal
country: Canada
facility: Centre Hospitalier Universitaire Sainte Justine
state: Quebec
city: Münster
country: Germany
facility: Münster University Hospital
city: Hyderabad
country: India
facility: Rainbow Children's Hospital
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Malpighi University Hospital
city: Florence
country: Italy
facility: Meyer Children's Hospital
city: Genova
country: Italy
facility: Instituto Giannina Gasilini
city: Rome
country: Italy
facility: Bambino Gesu Children's Hospital (Area Rossa Unit)
city: Rome
country: Italy
facility: Bambino Gesu Children's Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Kuala Lumpur
country: Malaysia
facility: University of Malaysia Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Auckland
country: New Zealand
facility: Starship Children's Hospital
city: Barakaldo
country: Spain
facility: Cruces University Hospital
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Faculty of Medicine Siriraj Hospital, Mahidol University
city: Bangkok
country: Thailand
facility: Faculty of Medicine Ramathibodi Hospital
city: Abu Dhabi
country: United Arab Emirates
facility: Shaikh Khalifa Medical City
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: UK
city: Leicester
country: United Kingdom
facility: University Hospital Leicester NHS Trust
Study officials:
affiliation: University of Pennsylvania
name: Martha AQ Curley, RN, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UH Rainbow Babies and Children's Hospital
name: Ira M. Cheifetz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beatrix Children's Hospital
name: Martin CJ Kneyber, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: David Wypij, PhD
role: PRINCIPAL_INVESTIGATOR
References: