PROSpect: Prone and Oscillation Pediatric Clinical Trial
- Conditions
- Acute Respiratory Distress Syndrome in Children
- Interventions
- Other: Either supine or prone positioning and either CMV or HFOV
- Registration Number
- NCT03896763
- Lead Sponsor
- University of Pennsylvania
- 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.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 600
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Prone / CMV Either supine or prone positioning and either CMV or HFOV Prone positioning and conventional mechanical ventilation Supine / HVOF Either supine or prone positioning and either CMV or HFOV Supine positioning and high-frequency oscillatory ventilation Supine / CMV Either supine or prone positioning and either CMV or HFOV Supine positioning and conventional mechanical ventilation Prone / HFOV Either supine or prone positioning and either CMV or HFOV Prone positioning and high-frequency oscillatory ventilation
- Primary Outcome Measures
Name Time Method Ventilator-free Days (VFD) 28 days Our primary research hypothesis is that children with severe PARDS randomized to either prone positioning or HFOV will demonstrate more ventilator-free days. We hypothesize that a superior treatment would improve VFD by at least 2 days, a clinically meaningful difference. VFD is the number of days within 28 days that a patient is alive and free of mechanical ventilation. Improvement in VFD will be considered within the context of patient safety; specifically, patients must also exhibit a similar safety profile.
- Secondary Outcome Measures
Name Time Method Nonpulmonary organ failure-free days (OFFD) 28 days Our secondary research hypothesis is that children with severe PARDS randomized to either prone positioning or HFOV will demonstrate more more nonpulmonary organ failure-free days. OFFD is the number of days within 28 days that a patient is alive and free of clinically significant non-pulmonary organ failure. Nonpulmonary organ failure-free days will be calculated based on the clinically important nonpulmonary organ systems (neurologic, cardiovascular, renal and hematologic) using nonpulmonary PEdiatric Logistic Organ Dysfunction-2 (PELOD-20 scores.
Trial Locations
- Locations (48)
Stanford Children's Health
🇺🇸Palo Alto, California, United States
Children's Hospital Orange County
🇺🇸Orange, California, United States
Penn State Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
Guangzhou Women & Children's Hospital (Yuexiu)
🇨🇳Guangzhou, China
Ann & Robert Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
University of New Mexico Children's Hospital
🇺🇸Albuquerque, New Mexico, United States
University of Iowa Stead Family Chlldren's Hospital
🇺🇸Iowa City, Iowa, United States
Cohen Children's Medical Center
🇺🇸Queens, New York, United States
Riley Hospital for Children at IU Health
🇺🇸Indianapolis, Indiana, United States
Duke Children's Hospital
🇺🇸Durham, North Carolina, United States
Children's Hospital of San Antonio
🇺🇸San Antonio, Texas, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
Perth Children's Hospital
🇦🇺Perth, Western Australia, Australia
Children's of Alabama
🇺🇸Birmingham, Alabama, United States
Children's Hospital at Oklahoma University Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Children's Hospital and Medical Center
🇺🇸Omaha, Nebraska, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Policlinico S. Orsola-Malpighi University Hospital
🇮🇹Bologna, Italy
Faculty of Medicine Ramathibodi Hospital
🇹🇭Bangkok, Thailand
Bambino Gesu Children's Hospital (Area Rossa Unit)
🇮🇹Rome, Italy
Bloomberg Children's Center, Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Medical City Dallas
🇺🇸Dallas, Texas, United States
Children's Health Dallas
🇺🇸Dallas, Texas, United States
LeBonheur Children's Hospital
🇺🇸Memphis, Tennessee, United States
Queensland Children's Hospital
🇦🇺South Brisbane, Queensland, Australia
Children's Hospital at Westmead
🇦🇺Sydney, Australia
Sabara Hospital Infantil
🇧🇷Sao Paulo, Brazil
Guangzhou Women & Children's Hospital (Newtown)
🇨🇳Guangzhou, Guangzhou, China
Centre Hospitalier Universitaire Sainte Justine
🇨🇦Montréal, Quebec, Canada
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Rainbow Children's Hospital
🇮🇳Hyderabad, India
Instituto Giannina Gasilini
🇮🇹Genova, Italy
Meyer Children's Hospital
🇮🇹Florence, Italy
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Bambino Gesu Children's Hospital
🇮🇹Rome, Italy
University of Malaysia Medical Center
🇲🇾Kuala Lumpur, Malaysia
Starship Children's Hospital
🇳🇿Auckland, New Zealand
Cruces University Hospital
🇪🇸Barakaldo, Spain
King Chulalongkorn Memorial Hospital
🇹🇭Bangkok, Thailand
Faculty of Medicine Siriraj Hospital, Mahidol University
🇹🇭Bangkok, Thailand
Shaikh Khalifa Medical City
🇦🇪Abu Dhabi, United Arab Emirates
Birmingham Children's Hospital
🇬🇧Birmingham, UK, United Kingdom
University Hospital Leicester NHS Trust
🇬🇧Leicester, United Kingdom
Kapiolani Medical Center for Women and Children
🇺🇸Honolulu, Hawaii, United States
CS Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States