What is the mechanism of action of this treatment?

The most common treatments for respiratory insufficiency, such as lung-protective ventilation and extracorporeal membrane oxygenation (ECMO), work by minimizing lung injury and improving gas exchange. Lung-protective ventilation uses lower tidal volumes to reduce mechanical stress on the lungs, thereby preventing ventilator-associated lung injury. ECMO, particularly veno-venous ECMO (VV-ECMO), facilitates CO2 removal and oxygenation outside the body, allowing the lungs to rest and heal. These treatments are crucial for respiratory insufficiency patients as they reduce the risk of further lung damage and improve overall respiratory function, enhancing the chances of recovery.

What side effects are associated with this type of intervention?

Common treatments for respiratory insufficiency, such as mechanical ventilation and extracorporeal membrane oxygenation (ECMO), have notable side effects. Mechanical ventilation can lead to ventilator-associated lung injury (VALI), including barotrauma, volutrauma, and atelectasis. ECMO, which helps reduce the intensity of mechanical ventilation, can cause bleeding, infection, and thromboembolic events. These side effects highlight the need for careful monitoring and management during treatment.

What prior FDA approvals exist?

The FDA has approved several treatments for respiratory insufficiency that aim to reduce lung injury by minimizing mechanical ventilation intensity and facilitating CO2 removal. One notable example is Extracorporeal Membrane Oxygenation (ECMO), which has been used in severe cases of respiratory failure to provide cardiac and respiratory support. Additionally, various mechanical ventilation strategies, such as low tidal volume ventilation, have been approved to minimize lung injury. While specific drugs directly facilitating CO2 removal are less common, supportive therapies like sedatives and neuromuscular blockers are often used in conjunction with these mechanical strategies to optimize patient outcomes.

What other types of research exist?

Promising novel alternatives to Ultra-Low Intensity Ventilation facilitated by CO2 removal through VV-ECMO for respiratory insufficiency patients include: 1) Ventilation strategies targeting lung-inflating (driving) pressure instead of tidal volume, 2) Strategies aiming to maintain optimal breathing effort to prevent diaphragm atrophy and injury, and 3) Noninvasive ventilation methods combined with mechanical insufflation-exsufflation techniques.

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Adaptive Ventilation Strategies + Corticosteroids for Critical Respiratory Insufficiency (PRACTICAL Trial)

N/A

Recruiting

Led By Lorenzo Del Sorbo, MD

Research Sponsored by Ewan Goligher

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Have already received 10 days of corticosteroid specifically for acute respiratory failure

Ongoing AHRF requiring HFNC, NIV, or invasive ventilation

Must not have

Contraindications to limited anticoagulation

Patients over 65 years of age

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing new ways to help patients with severe breathing problems. It includes using special machines to remove carbon dioxide from the blood, trying new ventilator methods, and giving steroids early. These treatments aim to improve breathing and reduce lung damage.

Who is the study for?

Adults over 18 with acute hypoxemic respiratory failure (AHRF) needing high-flow nasal cannula, non-invasive or invasive ventilation can join. They must have had corticosteroids for AHRF for at least 10 days and not be suffering from conditions like heart failure or pulmonary embolism. Exclusions include allergy to dexamethasone, severe brain injury, certain contraindications to anticoagulation, previous neuromuscular disorders, suspected COVID-19 infection among others.

What is being tested?

The trial is testing various interventions: usual care without extended corticosteroids; different mechanical ventilation strategies such as ultra-protective ventilation facilitated by ECMO and driving pressure-limited ventilation; early versus extended doses of corticosteroids in patients with persistent AHRF.

What are the potential side effects?

Potential side effects may include complications related to mechanical ventilation such as lung damage or infections, issues due to prolonged use of corticosteroids like weakened bones or muscle weakness, and risks associated with ECMO including bleeding or blood clots.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been treated with corticosteroids for acute respiratory failure for 10 days.

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I am currently on high-flow oxygen or ventilation support.

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I am 18 years old or older.

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My low oxygen levels are not due to heart failure, fluid in lungs, or blood clots.

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I am experiencing severe difficulty breathing due to low oxygen levels.

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I am on a breathing machine but not on ECMO, meeting specific lung flexibility criteria.

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I was admitted to the ICU less than 3 days ago.

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I have had severe breathing issues with low oxygen levels for at least 6 hours.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I cannot take certain blood thinners.

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I am over 65 years old.

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I have had severe low oxygen levels for more than 6 hours.

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My weight is more than 1kg for every cm of my height.

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I have long-term breathing problems with high CO2 levels.

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My care is focused on comfort and quality of life, not curing my illness.

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I have severe breathing issues with high CO2 levels and low pH for over 6 hours.

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I need to take corticosteroids for my condition.

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I have not taken corticosteroids in the last 14 days.

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I have a severe brain injury with a low consciousness level.

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I have been diagnosed with a neuromuscular disorder.

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I am on a life support machine but not on a mechanical ventilator.

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I am expected to be discharged from the ICU today.

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I have severe breathing issues with high CO2 levels and low pH for over 6 hours.

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I am currently taking corticosteroids for a reason other than cancer.

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I was admitted to the hospital for a recent brain injury.

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I am expected to have my breathing tube removed today.

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My breathing problems are due to COVID-19.

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I have been diagnosed with bleeding in my lungs due to vasculitis.

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I have had severe low oxygen levels in my blood for more than 6 hours.

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My weight was under 35 kg when I was admitted to the hospital.

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I am on low flow oxygen therapy of 15L/min or less.

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I use a ventilator at home but not just for sleep apnea.

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I expect to be on a breathing machine for less than 48 hours.

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I am suspected of or confirmed to have COVID-19.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

IMV domain - adherence to LDPVS management (LANDMARK RCT)

IMV domain - probability of achieving and maintaining lung- and diaphragm-protective targets during mechanical ventilation (LANDMARK RCT)

IMV domain - ventilator-free days to day 28 in DPL vs LPV (DRIVE RCT)

+1 more

Secondary study objectives

Complications from corticosteroids.

Days alive and at home to day 90

Diaphragm thickness

+25 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Ultra-protective ventilation facilitated by extracorporeal carbon dioxide removal (ULTIMATE) domainExperimental Treatment2 Interventions

Patients with acute hypoxemic respiratory failure in the high elastance state will be randomized to ultra-protective ventilation facilitated by extracorporeal carbon dioxide removal or to conventional lung-protective ventilation.

Group II: The Corticosteroid Early and Extended (CORT-E2) Randomized Controlled Trial domainExperimental Treatment4 Interventions

Patients with acute hypoxemic respiratory failure (AHRF) requiring invasive or non-invasive respiratory support will be randomized in the Early Cohort to receive corticosteroid or usual care without corticosteroids. Patients treated with corticosteroids who still require invasive or non-invasive respiratory support after 10 days will be randomized in the Extended Cohort to extending corticosteroid use or stopping corticosteroids after 10 days.

Group III: Invasive Mechanical Ventilation (IMV) Strategies domainExperimental Treatment3 Interventions

Patients on invasive mechanical ventilation in the low elastance, high elastance, and ECLS states will be randomized to one of two or three mechanical ventilation interventions (including conventional lung-protective ventilation as a control group). Most sites will randomize patients to two arms (one of which is the control group, LPV). A subset of sites will randomize patients to all three arms.

0 / 33Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for respiratory insufficiency, such as lung-protective ventilation and extracorporeal membrane oxygenation (ECMO), work by minimizing lung injury and improving gas exchange. Lung-protective ventilation uses lower tidal volumes to reduce mechanical stress on the lungs, thereby preventing ventilator-associated lung injury. ECMO, particularly veno-venous ECMO (VV-ECMO), facilitates CO2 removal and oxygenation outside the body, allowing the lungs to rest and heal. These treatments are crucial for respiratory insufficiency patients as they reduce the risk of further lung damage and improve overall respiratory function, enhancing the chances of recovery.

Lung-Protective Ventilation Attenuates Mechanical Injury While Hypercapnia Attenuates Biological Injury in a Rat Model of Ventilator-Associated Lung Injury.The acute respiratory distress syndrome in 2013.Smoke inhalation injury.