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PROSpect: Prone and Oscillation Pediatric Clinical Trial

Not Applicable
Conditions
Acute Respiratory Distress Syndrome in Children
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
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
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 (49)

Children's of Alabama

🇺🇸

Birmingham, Alabama, United States

Banner Health

🇺🇸

Phoenix, Arizona, United States

Arkansas Children's Hospital

🇺🇸

Little Rock, Arkansas, United States

Children's Hospital Orange County

🇺🇸

Orange, California, United States

Stanford Children's Health

🇺🇸

Palo Alto, California, United States

Kapiolani Medical Center for Women and Children

🇺🇸

Honolulu, Hawaii, United States

Ann & Robert Lurie Children's Hospital of Chicago

🇺🇸

Chicago, Illinois, United States

Riley Hospital for Children at IU Health

🇺🇸

Indianapolis, Indiana, United States

University of Iowa Stead Family Chlldren's Hospital

🇺🇸

Iowa City, Iowa, United States

Norton Children's Hospital

🇺🇸

Louisville, Kentucky, United States

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Children's of Alabama
🇺🇸Birmingham, Alabama, United States
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