PROSpect: Prone and Oscillation Pediatric Clinical Trial

NCT ID: NCT03896763

Last Updated: 2026-02-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-01
• Study Completion Date: 2027-01-31

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.

Conditions

Acute Respiratory Distress Syndrome in Children

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Supine / CMV

Supine positioning and conventional mechanical ventilation

Group Type: EXPERIMENTAL

Either supine or prone positioning and either CMV or HFOV

Intervention Type: OTHER

Supine positioning: Subjects randomized to supine positioning will remain supine.

Prone positioning: Subjects randomized to prone positioning will be positioned prone ≥16 hours/day for a maximum of 28 days.

CMV strategy: Low tidal volume to obtain exhaled Vt of 5-7 ml/kg (ideal body weight), PIP goal limited to ≤ 28 cm H2O and lung recruitment maneuver to identify best PEEP then maintained per PEEP-FiO2 grid.

HFOV strategy: Frequency at 8-12 Hz, amplitude (delta-P) 60-90 and mPaw recruitment maneuver.

Prone / CMV

Prone positioning and conventional mechanical ventilation

Group Type: EXPERIMENTAL

Either supine or prone positioning and either CMV or HFOV

Intervention Type: OTHER

Supine positioning: Subjects randomized to supine positioning will remain supine.

Prone positioning: Subjects randomized to prone positioning will be positioned prone ≥16 hours/day for a maximum of 28 days.

CMV strategy: Low tidal volume to obtain exhaled Vt of 5-7 ml/kg (ideal body weight), PIP goal limited to ≤ 28 cm H2O and lung recruitment maneuver to identify best PEEP then maintained per PEEP-FiO2 grid.

HFOV strategy: Frequency at 8-12 Hz, amplitude (delta-P) 60-90 and mPaw recruitment maneuver.

Supine / HVOF

Supine positioning and high-frequency oscillatory ventilation

Group Type: EXPERIMENTAL

Either supine or prone positioning and either CMV or HFOV

Intervention Type: OTHER

Supine positioning: Subjects randomized to supine positioning will remain supine.

Prone positioning: Subjects randomized to prone positioning will be positioned prone ≥16 hours/day for a maximum of 28 days.

CMV strategy: Low tidal volume to obtain exhaled Vt of 5-7 ml/kg (ideal body weight), PIP goal limited to ≤ 28 cm H2O and lung recruitment maneuver to identify best PEEP then maintained per PEEP-FiO2 grid.

HFOV strategy: Frequency at 8-12 Hz, amplitude (delta-P) 60-90 and mPaw recruitment maneuver.

Prone / HFOV

Prone positioning and high-frequency oscillatory ventilation

Group Type: EXPERIMENTAL

Either supine or prone positioning and either CMV or HFOV

Intervention Type: OTHER

Supine positioning: Subjects randomized to supine positioning will remain supine.

Prone positioning: Subjects randomized to prone positioning will be positioned prone ≥16 hours/day for a maximum of 28 days.

CMV strategy: Low tidal volume to obtain exhaled Vt of 5-7 ml/kg (ideal body weight), PIP goal limited to ≤ 28 cm H2O and lung recruitment maneuver to identify best PEEP then maintained per PEEP-FiO2 grid.

HFOV strategy: Frequency at 8-12 Hz, amplitude (delta-P) 60-90 and mPaw recruitment maneuver.

Interventions

Either supine or prone positioning and either CMV or HFOV

Supine positioning: Subjects randomized to supine positioning will remain supine.

Prone positioning: Subjects randomized to prone positioning will be positioned prone ≥16 hours/day for a maximum of 28 days.

CMV strategy: Low tidal volume to obtain exhaled Vt of 5-7 ml/kg (ideal body weight), PIP goal limited to ≤ 28 cm H2O and lung recruitment maneuver to identify best PEEP then maintained per PEEP-FiO2 grid.

HFOV strategy: Frequency at 8-12 Hz, amplitude (delta-P) 60-90 and mPaw recruitment maneuver.

Intervention Type: OTHER

Other Intervention Names

Supine positioning; Prone positioing; Conventional mechanical ventilation (CMV); High frequency oscillatory ventilation (HFOV)

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.

• 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

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

• Minimum Eligible Age: 2 Weeks
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: collaborator

University Hospitals Cleveland Medical Center

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Martha A.Q. Curley, PhD, RN

Ruth M. Colket Endowed Chair in Pediatric Nursing

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Martha AQ Curley, RN, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Ira M. Cheifetz, MD

Role: PRINCIPAL_INVESTIGATOR

UH Rainbow Babies and Children's Hospital

Martin CJ Kneyber, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Beatrix Children's Hospital

David Wypij, PhD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Locations

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

Bloomberg Children's Center, Johns Hopkins University

Baltimore, Maryland, United States

CS Mott Children's Hospital

Ann Arbor, Michigan, United States

Children's Hospital and Medical Center

Omaha, Nebraska, United States

Cohen Children's Medical Center

Queens, New York, United States

Duke Children's Hospital

Durham, North Carolina, United States

UH Rainbow Babies & Children

Cleveland, Ohio, United States

Children's Hospital at Oklahoma University Medical Center

Oklahoma City, Oklahoma, United States

Penn State Children's Hospital

Hershey, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

LeBonheur Children's Hospital

Memphis, Tennessee, United States

Medical City Dallas

Dallas, Texas, United States

Children's Health Dallas

Dallas, Texas, United States

Texas Children's Hospital

Houston, Texas, United States

Children's Hospital of San Antonio

San Antonio, Texas, United States

Inova Fairfax Medical Campus

Falls Church, Virginia, United States

American Family Children's Hospital, University of Wisconsin

Madison, Wisconsin, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Hospital de Pediatría J. P. Garrahan. SAMIC

Buenos Aires, Buenos Aires F.D., Argentina

Perth Children's Hospital

Perth, Western Australia, Australia

Children's Hospital at Westmead

Sydney, , Australia

Sabara Hospital Infantil

São Paulo, Brazil, Brazil

Hospital SEPACO

São Paulo, , Brazil

Centre Hospitalier Universitaire Sainte Justine

Montreal, Quebec, Canada

Münster University Hospital

Münster, , Germany

Rainbow Children's Hospital

Hyderabad, , India

Hadassah Medical Center

Jerusalem, , Israel

Meyer Children's Hospital

Florence, Italy, Italy

Bambino Gesu Children's Hospital (Area Rossa Unit)

Rome, Italy, Italy

Instituto Giannina Gasilini

Genova, , Italy

University of Malaysia Medical Center

Kuala Lumpur, , Malaysia

University Medical Center Groningen

Groningen, , Netherlands

Chonnam National University Hospital

Gwangju, , South Korea

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Faculty of Medicine Siriraj Hospital, Mahidol University

Bangkok, , Thailand

Faculty of Medicine Ramathibodi Hospital

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

Countries

United States; Argentina; Australia; Brazil; Canada; Germany; India; Israel; Italy; Malaysia; Netherlands; South Korea; Thailand; United Arab Emirates; United Kingdom

References

Kneyber MCJ, Cheifetz IM, Asaro LA, Graves TL, Viele K, Natarajan A, Wypij D, Curley MAQ; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Protocol for the Prone and Oscillation Pediatric Clinical Trial ( PROSpect ). Pediatr Crit Care Med. 2024 Sep 1;25(9):e385-e396. doi: 10.1097/PCC.0000000000003541. Epub 2024 May 28.

Reference Type: DERIVED

PMID: 38801306 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://www.prospect-network.org/

Study Website

Other Identifiers

5UH3HL141736-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

831295

Identifier Type: -

Identifier Source: org_study_id