Ventilation Strategies for Acute Respiratory Distress Syndrome in Children

(PARMA Trial)

Overseen By Stephen Famularo III, B.A.

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital of Philadelphia

Disqualifiers: Heart disease, Airway disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 days

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best ventilator settings for children with acute respiratory distress syndrome (ARDS), a severe lung condition. Researchers seek to discover whether high driving pressure mechanical ventilation or low driving pressure mechanical ventilation benefits children more than current adult-based settings. Children who experience sudden breathing difficulties and require machine assistance for up to a week may qualify for this study. The results will guide future ventilator use for children. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of children, providing valuable insights for future care.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that these ventilation strategies are safe for children with ARDS?

Previous studies have linked high driving pressure in mechanical ventilation to certain risks. Research shows that higher driving pressures can lead to longer ventilator use. Additionally, high driving pressure correlates with an increased risk of death in children under these conditions.

Conversely, studies on low driving pressure in mechanical ventilation suggest it may be safer. Lower pressure settings are associated with better survival rates. Specifically, keeping the driving pressure below 15 cm H2O significantly reduces health problems in children with breathing issues.

Researchers are studying both treatment methods to determine which is more effective for children with acute respiratory distress syndrome (ARDS). The research aims to identify the safest and most beneficial settings for young patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores how different ventilation strategies can impact children with Acute Respiratory Distress Syndrome (ARDS). Most current treatments focus on standard mechanical ventilation settings and supportive care. This trial, however, examines the effects of using high versus low driving pressures in mechanical ventilation. The high driving pressure approach involves a setting of 25 cmH2O, which might improve oxygenation, while the low driving pressure is set at 15 cmH2O, potentially reducing lung injury. By comparing these two approaches, researchers hope to find out which strategy offers better outcomes for young patients, ultimately leading to improved and more personalized care.

What evidence suggests that this trial's ventilation strategies could be effective for ARDS in children?

This trial will compare two ventilation strategies for children with acute respiratory distress syndrome (ARDS): High Driving Pressure Mechanical Ventilation and Low Driving Pressure Mechanical Ventilation. Research has shown that using lower pressure during mechanical breathing support can improve survival in patients with ARDS. Studies suggest that high pressure increases the risk of death and prolongs ventilator use. In contrast, low pressure has been linked to better outcomes for those needing this support. This evidence suggests that low pressure might be more effective for treating ARDS in children. ^{1 2 4 6 7}

Who Is on the Research Team?

Nadir Yehya, MD, MSCE

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for children with a serious lung condition called ARDS, who are on breathing machines. It's to find out if ventilator settings made for adults work well in kids or if there's a better way.

Inclusion Criteria

Hypoxemia defined as PaO2/FIO2 > 300 (or SpO2/FIO2 > 315 on Positive End-Expiratory Pressure (PEEP) ≥ 5 cmH2O on two consecutive measurements 4 hours apart and sustained at the time of consent and randomization

Bilateral opacities on chest radiograph as determined by radiologist, clinical attending, or PI

I have been on a ventilator for 7 days or less since my condition started.

Exclusion Criteria

Previous enrollment in this study

Severe moribund state not expected to survive > 72 hours

I have a heart condition from birth that hasn't been fully treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive mechanical ventilation with either high or low driving pressure settings

Up to 28 days

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days

Regular assessments until hospital discharge

What Are the Treatments Tested in This Trial?

Interventions

• High Driving Pressure Mechanical Ventilation
• Low Driving Pressure Mechanical Ventilation

Trial Overview The study compares two ways of using ventilators: one uses high pressure and the other low pressure to help the children breathe. The goal is to see which method helps more.

How Is the Trial Designed?

Group I: High Driving Pressure Mechanical Ventilation Active Control 1 Intervention

A participant who is already on the breathing machine will have the driving pressure set to 25 cmH2O (rate of pressure delivery). All other standard clinical care for this participant will stay the same based on what their clinical team chooses to do.

Group II: Low Driving Pressure Mechanical Ventilation Active Control 1 Intervention

A participant who is already on the breathing machine will have the driving pressure set to 15 cmH2O (rate of pressure delivery). All other standard clinical care for this participant will stay the same based on what their clinical team chooses to do.

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8897270/

Driving pressure is associated with outcome in pediatric ... Conclusions: Higher driving pressure was independently associated with increased time to extubation in mechanically ventilated children. Dynamic ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMsa1410639

Driving Pressure and Survival in the Acute Respiratory ... A 1-SD increment in ΔP (approximately 7 cm of water) was associated with increased mortality (relative risk, 1.41; 95% confidence interval [CI], ...

3. wjgnet.com wjgnet.com/2220-3141/full/v14/i2/101377.htm

Driving pressure in acute respiratory distress syndrome for ... Studies indicate that lower DP levels are significantly associated with improved survival rates in ARDS patients.

4. journals.lww.com journals.lww.com/ccejournal/fulltext/2024/03000/investigating_the_association_between_dynamic.6.aspx

Investigating the Association Between Dynamic Driving... A significant increase in risk in the hazard of death was found for every hour of exposure to high intensities of driving pressure (≥ 15 cm H 2O) (HR 1.002; 95% ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11019631/

Driving pressure in mechanical ventilation: A review - PMC Recent studies have shown a plausible association between ∆P and improved survival in patients with acute respiratory distress syndrome (ARDS)[5,7-13].

6. turkishjic.org turkishjic.org/article/view/534

Relationship Between Driving Pressure During the First 24 ... Driving pressure was significantly associated with an increased risk of mortality among mechanically ventilated both pARDS and non-pARDS patients.

7. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-021-03853-6

Mechanical power in pediatric acute respiratory distress ... Higher mechanical power is associated with fewer 28-day ventilator-free days in children with pediatric acute respiratory distress syndrome.