Acute Respiratory Distress Syndrome in Children Clinical Trial
Official title:
PROSpect: Prone and Oscillation Pediatric Clinical Trial
| Verified date | September 2023 |
| Source | University of Pennsylvania |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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).
| Status | Enrolling by invitation |
| Enrollment | 800 |
| Est. completion date | July 31, 2026 |
| Est. primary completion date | January 1, 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Weeks to 20 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Perth Children's Hospital | Perth | Western Australia |
| Australia | Queensland Children's Hospital | South Brisbane | Queensland |
| Australia | Children's Hospital at Westmead | Sydney | |
| Brazil | Sabara Hospital Infantil | Sao Paulo | |
| Canada | Centre Hospitalier Universitaire Sainte Justine | Montréal | Quebec |
| China | Guangzhou Women & Children's Hospital (Newtown) | Guangzhou | Guangzhou |
| China | Guangzhou Women & Children's Hospital (Yuexiu) | Guangzhou | |
| India | Rainbow Children's Hospital | Hyderabad | |
| Israel | Hadassah Medical Center | Jerusalem | |
| Italy | Policlinico S. Orsola-Malpighi University Hospital | Bologna | |
| Italy | Meyer Children's Hospital | Florence | |
| Italy | Instituto Giannina Gasilini | Genova | |
| Italy | Bambino Gesu Children's Hospital | Rome | |
| Italy | Bambino Gesu Children's Hospital (Area Rossa Unit) | Rome | |
| Malaysia | University of Malaysia Medical Center | Kuala Lumpur | |
| Netherlands | University Medical Center Groningen | Groningen | |
| New Zealand | Starship Children's Hospital | Auckland | |
| Spain | Cruces University Hospital | Barakaldo | |
| Thailand | Faculty of Medicine Ramathibodi Hospital | Bangkok | |
| Thailand | Faculty of Medicine Siriraj Hospital, Mahidol University | Bangkok | |
| Thailand | King Chulalongkorn Memorial Hospital | Bangkok | |
| United Arab Emirates | Shaikh Khalifa Medical City | Abu Dhabi | |
| United Kingdom | Birmingham Children's Hospital | Birmingham | UK |
| United Kingdom | University Hospital Leicester NHS Trust | Leicester | |
| United Kingdom | University Hospital Southampton NHS Foundation Trust | Southampton | |
| United States | University of New Mexico Children's Hospital | Albuquerque | New Mexico |
| United States | CS Mott Children's Hospital | Ann Arbor | Michigan |
| United States | Bloomberg Children's Center, Johns Hopkins University | Baltimore | Maryland |
| United States | Children's of Alabama | Birmingham | Alabama |
| United States | The Children's Hospital of Montefiore | Bronx | New York |
| United States | Medical University of South Carolina | Charleston | South Carolina |
| United States | Ann & Robert Lurie Children's Hospital of Chicago | Chicago | Illinois |
| United States | Children's Health Dallas | Dallas | Texas |
| United States | Medical City Dallas | Dallas | Texas |
| United States | Duke Children's Hospital | Durham | North Carolina |
| United States | Connecticut Children's Medical Center | Hartford | Connecticut |
| United States | Penn State Children's Hospital | Hershey | Pennsylvania |
| United States | Kapiolani Medical Center for Women and Children | Honolulu | Hawaii |
| 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 | Arkansas Children's Hospital | Little Rock | Arkansas |
| United States | Norton Children's Hospital | Louisville | Kentucky |
| United States | LeBonheur Children's Hospital | Memphis | Tennessee |
| United States | Children's Hospital of Wisconsin | Milwaukee | Wisconsin |
| United States | Yale University | New Haven | Connecticut |
| 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 Orange County | Orange | California |
| United States | Stanford Children's Health | Palo Alto | California |
| United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
| United States | Cohen Children's Medical Center | Queens | New York |
| United States | Children's Hospital of San Antonio | San Antonio | Texas |
| United States | UCSF Benioff Children's | San Francisco | California |
| United States | Seattle Children's Hospital | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| University of Pennsylvania | Boston Children's Hospital, National Heart, Lung, and Blood Institute (NHLBI), University Hospitals Cleveland Medical Center, University Medical Center Groningen |
United States, Australia, Brazil, Canada, China, India, Israel, Italy, Malaysia, Netherlands, New Zealand, Spain, Thailand, United Arab Emirates, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Interaction effects of prone positioning with HFOV on VFDs - number of ventilator-free days | The number of ventilator-free days (VFD) will be compared between children randomized to prone/CMV and supine/HFOV to those randomized to prone/HFOV. VFD is the number of days within 28 days that a patient is alive and free of mechanical ventilation. | 28 days | |
| Other | 90-day in-hospital mortality | Deaths from all causes will be monitored through hospital discharge or day 90 (whichever occurs first). The primary and secondary causes of death (as specified on the death certificate) will be recorded to allow us to probe the cause of death in PARDS. | 90 days | |
| Other | Duration of mechanical ventilation (among survivors) | Duration of mechanical ventilation provides a prospective evaluation of ventilator support independent of mortality. The duration of mechanical ventilation is defined as the time from day 0 (intubation) to the first time the endotracheal tube is continuously absent for at least 24 hours. For subjects with tracheostomies, duration of mechanical ventilation is defined as the time of initiation of assisted breathing to the first time positive pressure is <5 cm H2O (continuous or bi-level) for at least 24 hours. Duration of mechanical ventilation will be considered to be 28 days for subjects still intubated on day 28, and will be calculated for subjects who survive to hospital discharge or day 90 (whichever occurs first). | 28 days, 90 days | |
| Other | PICU and hospital length of stay (among survivors) | PICU length of stay (LOS) is defined as the time from day 0 (intubation) to the time of PICU discharge, while hospital LOS is defined as the time from day 0 to the time of hospital discharge. PICU and hospital LOS will be considered to be 90 days for subjects still in the PICU/hospital on day 90, and will be calculated for subjects who survive to hospital discharge or day 90 (whichever occurs first). | 90 days | |
| Other | Post PICU discharge functional status | Pre and post PICU functional status will be compared. Functional status will be assessed using the Pediatric Cerebral Performance (PCPC), Pediatric Overall Performance Category (POPC) and Functional Status Scale (FSS) score. The PCPC and POPC quantify short-term cognitive impairments and functional morbidity. Scores range from 1 to 6 for both scales with 1: good, 2: mild disability, and 6: brain death. The FSS is a valid and reliable assessment method to quantify functional status. The FSS includes 6 domains: mental status, sensory functioning, communication, motor function, feeding, and respiratory. Scores for each domain range from 1 (normal) to 5 (very severe dysfunction) with total scores ranging from 6 to 30. | 1, 3, 6, 12 months post PICU discharge | |
| Other | Post PICU discharge health-related quality of life (HRQL) | Pre and post PICU health-related quality of life will be compared using the PedsQL 4.0 Generic Core Scales and Infant Scales - Acute Version They are 23-item child self-report and parent proxy-report scales with four domains: physical functioning, emotional functioning, social functioning, and school functioning. Scale ranges from 0 to 100, with higher scores indicating fewer problems. The PedsQL Infant Scales consist of 36-45 questions, depending on age, with 5 domains: physical functioning, physical symptoms, emotional functioning, social functioning, and cognitive functioning. The PedsQL™ Multi-dimensional Fatigue Scale - Acute Version is an 18-item scale that encompasses three domains: General Fatigue, Sleep/Rest Fatigue and Cognitive Fatigue. Higher scores indicate better HRQOL. PedsQL Pediatric Pain Questionnaire is a generic pain instrument. Subjects capable of self-reporting identify a point on a 100 mm line that best shows the worst pain they experienced in the past week. | 1, 3, 6, 12 months post PICU discharge | |
| Primary | Ventilator-free Days (VFD) | 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. | 28 days | |
| Secondary | Nonpulmonary organ failure-free days (OFFD) | 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. | 28 days |