Precision Ventilation for Acute Respiratory Distress Syndrome

(PREVENT VILI Trial)

Recruiting at 27 trial locations

Overseen By Nancy Ringwood, RN

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Beth Israel Deaconess Medical Center

Disqualifiers: Severe brain injury, Neuromuscular disease, Severe liver disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

1100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two ventilator methods for individuals with Acute Respiratory Distress Syndrome (ARDS), a serious lung condition. The goal is to determine if a personalized ventilator adjustment method, called Precision Ventilation, improves survival more effectively than the usual method. Participants will either receive standard care or have their ventilators adjusted to match normal lung stress levels in healthy individuals. The trial seeks participants who have been on a ventilator for ARDS within the last four days, with worsening breathing problems that began within a week. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially life-saving advancements in ARDS treatment.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that precision ventilation, a personalized method of using breathing machines, can be safe for patients with Acute Respiratory Distress Syndrome (ARDS). This technique adjusts the machine to match each person's lung condition, aiming to reduce lung damage. By mimicking normal breathing patterns, it may lower the risk of complications. Although researchers are still studying this personalized approach, this stage of research typically indicates strong evidence of safety and rare side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Precision Ventilation approach for Acute Respiratory Distress Syndrome (ARDS) because it offers a personalized way to manage ventilation. Unlike standard ventilation methods that follow a one-size-fits-all protocol, Precision Ventilation tailors the ventilator settings to mimic the lung stress levels of healthy breathing, considering factors like pleural pressure and tidal volume. This method aims to minimize lung injury by adjusting settings such as PEEP and FiO2 based on individual patient needs. By optimizing ventilation in this way, the trial hopes to improve outcomes for ARDS patients, potentially reducing the risks associated with conventional ventilation strategies.

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

This trial will compare two ventilation strategies for patients with ARDS. Research has suggested that tailoring ventilator settings to each patient's lung condition can reduce lung damage and improve outcomes. Participants in the "Precision Ventilation" arm will have ventilator settings adjusted to mimic relaxed breathing in healthy adults, potentially improving survival rates. Meanwhile, the "Guided Usual Care" arm will follow standard mechanical ventilation practices with protocol-based adjustments. Although some studies found no major differences between standard care and personalized methods, this strategy still shows promise for reducing complications. ^{2 3 5 6 7}

Who Is on the Research Team?

Daniel Talmor, MD MPH

Principal Investigator

Beth Israel Deaconess Medical Center

Are You a Good Fit for This Trial?

Adults over 18 with severe breathing problems due to Acute Respiratory Distress Syndrome (ARDS) can join this trial. They must be early in their ARDS course, currently on a ventilator, and not have been on it for more than 4 days. People with certain conditions like severe brain injury, recent major chest or stomach surgery, chronic lung issues, or those at high risk of bleeding are excluded.

Inclusion Criteria

I have been severely short of breath for no more than 10 days.

I was diagnosed with severe lung problems less than 2 days ago.

My symptoms started or got worse within a week of a medical event.

Exclusion Criteria

I have had issues or surgery related to my esophagus.

I have a muscle condition that affects my ability to breathe on my own.

I need extra oxygen daily, have lung scarring, or had a lung transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either precision ventilation or guided usual care for ARDS

28 days

Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days

Outcome Assessment

Assessment of primary and secondary outcomes including mortality and ventilator-free days

60 days

What Are the Treatments Tested in This Trial?

Interventions

• Guided Usual Care Ventilation
• Precision Ventilation

Trial Overview The study is testing two ways to help patients breathe using a machine: the usual method versus a new 'precision' approach tailored to reduce lung stress. The main goal is to see if the personalized method improves survival rates for people with ARDS.

How Is the Trial Designed?

Group I: Precision ventilation Experimental Treatment 1 Intervention

Ventilator support will be calibrated to maintain the range of lung stress typical of relaxed breathing in healthy adults. The ventilator management protocol takes into account pleural pressure, tidal volume and driving pressure, fraction of inspired oxygen (FiO2) and oxygen saturation (SpO2), and positive end-expiratory pressure (PEEP) titration.

Group II: Guided usual care Active Control 1 Intervention

Ventilator support will be managed by the clinical team per usual care with select protocol-based guard rails to avoid practice extremes beyond the current body of evidence. PEEP titration will be performed by the clinical team within the limits set in. The allowable combinations of PEEP and FiO2 in the control arm reflect pre-intervention usual care observed at baseline in the recent large federally-funded multicenter ARDS trials.

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

NYU Langone Health

Collaborator

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

Current strategies for treating acute respiratory distress syndrome (ARDS) focus on minimizing ventilation-induced lung injury (VILI) by personalizing mechanical ventilation based on individual patient respiratory mechanics.

Understanding the specific biophysical mechanisms of VILI, such as volutrauma and barotrauma, allows for better assessment and tailoring of lung-protective ventilation strategies, potentially reducing the risk of multiorgan failure associated with ARDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bedside respiratory physiology to detect risk of lung injury in acute respiratory distress syndrome. Beitler, JR.[2020]

Mechanical ventilation can either worsen lung injury in patients with or at risk for ARDS or help reduce mortality if properly adjusted, highlighting the importance of personalized ventilation strategies.

Current practices often use a standard approach for setting tidal volume and PEEP, but evidence suggests that optimizing PEEP based on individual lung pathology rather than solely on oxygenation could improve patient outcomes, though no consensus exists on the best method for personalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalizing mechanical ventilation according to physiologic parameters to stabilize alveoli and minimize ventilator induced lung injury (VILI). Nieman, GF., Satalin, J., Andrews, P., et al.[2020]

In a study of 30 patients undergoing thoracic surgery, individualized positive end-expiratory pressure (PEEP) significantly improved oxygenation and lung mechanics during one-lung ventilation compared to a standardized PEEP of 5 cm·H2O.

The study group maintained higher arterial oxygenation levels (306 mm·Hg) and showed significant improvements in static compliance after adjusting PEEP, while the control group experienced decreased oxygenation, highlighting the efficacy of individualized PEEP in enhancing respiratory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Setting individualized positive end-expiratory pressure level with a positive end-expiratory pressure decrement trial after a recruitment maneuver improves oxygenation and lung mechanics during one-lung ventilation. Ferrando, C., Mugarra, A., Gutierrez, A., et al.[2022]

Recent research highlights the importance of tailoring mechanical ventilation strategies to individual patients' risk of lung injury, particularly in cases of acute respiratory distress syndrome (ARDS), where patients may exhibit different inflammatory responses.

A precision medicine approach to lung-protective ventilation should consider factors such as the patient's biological and mechanical predispositions to lung injury, the benefits of interventions, and the potential adverse effects of necessary cointerventions, rather than relying on a one-size-fits-all strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung protection in acute respiratory distress syndrome: what should we target? Beitler, JR.[2022]

A multicenter trial involving 420 patients with moderate-to-severe ARDS found that personalizing mechanical ventilation based on lung morphology did not significantly reduce 90-day mortality compared to standard care (hazard ratio 1.01).

Misclassification of patients' lung morphology was common (21%), and those misclassified had higher mortality rates when treated with personalized ventilation, suggesting that accurate phenotyping of ARDS is crucial for effective treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial. Constantin, JM., Jabaudon, M., Lefrant, JY., et al.[2020]

In a study involving anaesthetized rabbits, individualized physiological variable ventilation (PVV) showed significantly less lung injury compared to conventional pressure-controlled ventilation (PC), with lower lung injury scores and wet-to-dry lung weight ratios, indicating better lung protection.

PVV maintained stable respiratory elastance and adequate gas exchange over a 7-hour period, suggesting it could be a beneficial ventilation strategy during prolonged anesthesia when natural breathing is absent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between neurally-assisted, controlled, and physiologically variable ventilation in healthy rabbits. Walesa, M., Bayat, S., Albu, G., et al.[2022]

A personalized mechanical ventilation strategy for patients with ARDS, which considers lung physiology, imaging, and biological phenotypes, may enhance treatment outcomes, but more research is needed before implementation in clinical settings.

Monitoring specific ventilatory parameters, such as low tidal volume and driving pressures, along with techniques like esophageal pressure monitoring, can help tailor ventilation settings to individual patient needs, potentially improving safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized mechanical ventilation in acute respiratory distress syndrome. Pelosi, P., Ball, L., Barbas, CSV., et al.[2021]

Citations

1. reporter.nih.gov reporter.nih.gov/project-details/10738959

Project Details - NIH RePORTER Results from this trial may establish a personalized approach to ARDS management that reduces morbidity and mortality and, by extension, decreases costs and ...

2. uclahealth.org uclahealth.org/clinical-trials/precision-ventilation-vs-standard-care-acute-respiratory

Precision Ventilation vs Standard Care for Acute ... The goal of this interventional study is to compare standard mechanical ventilation to a lung-stress oriented ventilation strategy in patients with Acute ...

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06066502

Precision Ventilation vs Standard Care for Acute Respiratory ... The goal of this interventional study is to compare standard mechanical ventilation to a lung-stress oriented ventilation strategy in patients with Acute ...

4. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-021-03686-3

Personalized mechanical ventilation in acute respiratory ... A recent clinical trial [65] found no differences in outcome between standard lung–protective ventilation and personalized ventilation based on ...

5. withpower.com withpower.com/trial/phase-3-respiratory-distress-syndrome-2024-117fb

Precision Ventilation for Acute Respiratory Distress ... Research suggests that personalizing mechanical ventilation to individual lung conditions can help reduce lung injury and improve outcomes in patients with ...

6. reporter.nih.gov reporter.nih.gov/project-details/10912795

2/2: PREcision VENTilation to attenuate ... Results from this trial may establish a personalized approach to ARDS management that reduces morbidity and mortality and, by extension, decreases costs and ...

7. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT06066502

Precision Ventilation vs Standard Care for Acute Respiratory ... The goal of this interventional study is to compare standard mechanical ventilation to a lung-stress oriented ventilation strategy in ...