CNEP + HFNC for Respiratory Insufficiency

Overseen By Jeremy Beitler, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Columbia University

Disqualifiers: Pregnancy, Asthma, COPD, others

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

Compensation: Varies

Number of Visits: 2

Duration: 4 hours

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a special breathing device, which uses a slight vacuum to help the chest expand, can improve breathing in people with lung injuries who require high-flow oxygen. The device, called Continuous Negative External Pressure (CNEP), is being tested both alone and in combination with high-flow nasal cannula (HFNC), which delivers oxygen at a high rate. Participants suitable for this trial have acute hypoxemic respiratory failure, meaning they struggle to get enough oxygen into their blood due to lung injury. They should have also started high-flow oxygen therapy within the last four days. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance treatment options for lung injuries.

Do I need to stop my current medications for this trial?

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

What prior data suggests that this breathing support device is safe for patients with lung injury?

Research has shown that high-flow nasal cannula (HFNC) therapy is generally safe and effective for individuals with breathing problems, such as those caused by COVID-19. Many seriously ill patients with respiratory issues have successfully used it. However, some risks include device malfunctions, discomfort, and difficulty swallowing.

Continuous negative external pressure (CNEP) is another treatment under study. Although detailed safety information on CNEP remains limited, its non-invasive design typically suggests a lower risk of harm.

HFNC and CNEP together aim to improve breathing with minimal risk. Prospective trial participants should consult their healthcare provider to determine if participation is suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for respiratory insufficiency because they explore the combination of Continuous Negative External Pressure (CNEP) with High-Flow Nasal Cannula (HFNC) therapy. Unlike traditional oxygen therapy, which primarily focuses on delivering supplemental oxygen, HFNC provides heated and humidified oxygen at high flow rates, improving oxygenation and reducing work of breathing. By adding CNEP, which applies negative pressure around the chest to enhance lung expansion, these treatments aim to improve lung function more effectively. This combination approach could offer a more comprehensive solution, potentially leading to faster and more sustained improvements in respiratory function.

What evidence suggests that this trial's treatments could be effective for acute hypoxemic respiratory failure?

Research has shown that high-flow nasal cannula (HFNC) therapy can assist people with breathing problems. HFNC delivers oxygen at high rates, easing the breathing process. This method benefits both children and adults with various respiratory issues. Continuous negative external pressure (CNEP) is another non-invasive technique that helps the chest expand, potentially improving breathing. In this trial, participants will receive different treatments, including HFNC alone or HFNC combined with varying levels of CNEP (CNEP10, CNEP20, or CNEP30). Combining HFNC and CNEP could offer enhanced support for individuals with serious lung injuries. Although further research is necessary, these therapies might improve breathing in patients with severe respiratory difficulties. ^{5 6 7 8 9}

Who Is on the Research Team?

Jeremy Beitler, MD, MPH

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

Adults with non-heart-related lung injury needing high-flow oxygen can join this trial. They must have started using a high-flow nasal cannula within the last four days and maintain certain oxygen levels. People with unreliable pulse-oximetry, chest injuries, severe blood pressure issues, do-not-intubate orders, or conditions affecting device fit like severe spine curvature cannot participate.

Inclusion Criteria

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

Your oxygen levels are at least 92%.

I need a high level of oxygen support.

Exclusion Criteria

My doctor has advised against me joining the trial.

You have a medical order that says not to use a breathing tube.

Your Glasgow coma score is less than 15.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Measurement

Perform baseline measures and wait for recovery

15 minutes

1 visit (in-person)

Treatment

Participants undergo 4 strategies of respiratory support with random treatment assignments

4 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• CNEP10
• CNEP20
• CNEP30
• HFNC + CNEP10
• HFNC + CNEP20
• HFNC + CNEP30
• HFNC only

Trial Overview The study tests if a non-invasive breathing support device called CNEP improves breathing in patients with acute hypoxemic respiratory failure. Participants will receive different levels of negative pressure (CNEP30, CNEP20, CNEP10) along with standard high-flow nasal cannula therapy to see which works best.

How Is the Trial Designed?

Group I: HFNC + CNEP30 Experimental Treatment 1 Intervention

Group II: HFNC + CNEP20 Experimental Treatment 1 Intervention

Group III: HFNC + CNEP10 Experimental Treatment 1 Intervention

Group IV: HFNC only Active Control 1 Intervention

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Published Research Related to This Trial

High-flow nasal cannulae (HFNC) show promise as a non-invasive respiratory support option for preterm infants, potentially offering similar benefits to nasal continuous positive airway pressure (NCPAP) in improving respiratory parameters, especially at flow rates above 2 liters/min.

Despite the feasibility of HFNC, there is still uncertainty regarding its overall efficacy and safety in preterm infants, highlighting the need for larger randomized trials before it can be widely recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-flow nasal cannulae for respiratory support of preterm infants: a review of the evidence. Manley, BJ., Dold, SK., Davis, PG., et al.[2012]

Nasal continuous positive airway pressure (nCPAP) is the preferred method for providing noninvasive respiratory support to preterm infants with respiratory distress syndrome, as it is more effective than high-flow nasal cannula (HFNC) in this role.

HFNC serves as a suitable alternative to nCPAP after extubation, indicating its usefulness in managing respiratory support in neonatal intensive care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nasal Continuous Positive Airway Pressure and High-Flow Nasal Cannula Today. Dani, C.[2021]

In a study of 30 extremely preterm infants (average gestational age of 27 weeks and birth weight of 930 g), high flow nasal cannula (HFNC) was associated with longer respiratory pauses compared to nasal continuous positive airway pressure (NCPAP), indicating potential differences in respiratory stability between the two methods.

HFNC also required higher levels of fraction of inspired oxygen (FiO2) than NCPAP, suggesting that while both are used for respiratory support, HFNC may necessitate more oxygen to maintain adequate saturation in these vulnerable infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiorespiratory behavior of preterm infants receiving continuous positive airway pressure and high flow nasal cannula post extubation: randomized crossover study. Kanbar, LJ., Shalish, W., Latremouille, S., et al.[2021]

In a study involving 372 preterm infants, high-flow nasal cannula (HFNC) was associated with a significantly higher rate of treatment failure (31%) compared to nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive-pressure ventilation (NIPPV) (16%) after extubation.

Factors such as histologic chorioamnionitis, treated patent ductus arteriosus, and younger corrected gestational age were identified as independent predictors of treatment failure when using HFNC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Controlled Trial of High-Flow Nasal Cannula in Preterm Infants After Extubation. Uchiyama, A., Okazaki, K., Kondo, M., et al.[2021]

In a study of 120 patients with acute hypoxemic respiratory failure, high-flow nasal cannula (HFNC) treatment resulted in significantly lower rates of abdominal distension compared to noninvasive positive-pressure ventilation (NPPV), indicating a safer profile for HFNC.

Both HFNC and NPPV showed similar effectiveness in preventing respiratory failure post-extubation, with no significant differences in key respiratory parameters or re-intubation rates, suggesting that HFNC may be a preferable option due to its lower incidence of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of outcomes of high-flow nasal cannula and noninvasive positive-pressure ventilation in patients with hypoxemia and various APACHE II scores after extubation. Shang, X., Wang, Y.[2021]

High-flow nasal cannula (HFNC) oxygen therapy is a safe and effective non-invasive treatment for children with respiratory illnesses, as demonstrated in a study of 66 children in a level 2 pediatric ward in South Africa, with no serious adverse events reported.

HFNC significantly reduced the need for transfer to higher-level care (level 3) for invasive ventilation, with only 24.2% of HFNC patients requiring such transfer compared to 100% in the historical cohort before HFNC was available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the use of high-flow nasal cannula oxygen therapy in hospitalised children at a regional hospital in the Cape Town Metro, South Africa. Hoffman, E., Reichmuth, KL., Cooke, ML.[2019]

In a study of very premature infants (≤28 weeks gestation and <1,250 g birth weight), using heated humidified high-flow nasal cannula (HHFNC) alongside nasal continuous positive airway pressure (NCPAP) significantly reduced the duration of NCPAP use by 50% compared to low-flow nasal cannula (LFNC).

HHFNC was associated with a lower incidence of nasal bridge lesions (0% vs. 13% in the NCPAP group) and improved cost-effectiveness by reducing overall treatment costs by 33%, while maintaining similar respiratory and non-respiratory outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heated humidified high-flow nasal cannula versus low-flow nasal cannula as weaning mode from nasal CPAP in infants ≤28 weeks of gestation. Fernandez-Alvarez, JR., Gandhi, RS., Amess, P., et al.[2021]

The in vitro study highlighted that a pressure-limiting valve is essential for the humidified high-flow nasal cannula (HFNC) system, especially at flows of 2 L/minute or higher, to maintain appropriate pressures without leaks.

In the in vivo study involving 15 newborns, while mean end-expiratory esophageal pressure (EEEP) levels were similar between nasal continuous positive airway pressure (NCPAP+6) and HFNC, a decrease in flow led to increased respiratory rates, indicating potential respiratory distress as flow diminished.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational study of humidified high-flow nasal cannula compared with nasal continuous positive airway pressure. Lampland, AL., Plumm, B., Meyers, PA., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-respiratory-insufficiency-2-2023-220a6

CNEP + HFNC for Respiratory Insufficiency High-flow nasal cannula (HFNC) oxygen therapy is a safe and effective non-invasive treatment for children with respiratory illnesses, as demonstrated in a ...

2. journals.physiology.org journals.physiology.org/doi/full/10.1152/japplphysiol.00416.2021?doi=10.1152/japplphysiol.00416.2021

High-flow nasal cannula compared with continuous ... When increasing HFNC flow, respiratory rate decreased by lengthening expiratory time, tidal volume did not change, and effort decreased (pressure-time product ...

3. journals.lww.com journals.lww.com/md-journal/fulltext/2025/07040/efficacy_and_safety_of_high_flow_nasal_cannula.1.aspx

Efficacy and safety of high-flow nasal cannula versus... HFNC therapy is as effective as NIV in mild to moderate RV dysfunction; nevertheless, NIV might be more advantageous for severe cases.

4. sciencedirect.com sciencedirect.com/science/article/pii/S001236922200441X

High-Flow Nasal Cannula Reduces Effort of Breathing But ... High-flow nasal cannula (HFNC) therapy reduces the effort of breathing in patients with bronchiolitis, but the mechanisms are not understood.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10667189/

High-flow nasal cannula oxygen versus conventional oxygen ... The effectiveness of high-flow nasal cannula oxygen therapy (HFNC) in patients with acute respiratory failure due to COVID-19 remains uncertain.

6. aacnjournals.org aacnjournals.org/ajcconline/article/34/2/95/32665/The-8-D-s-of-High-Flow-Nasal-Cannula-Risk-A

The “8 D's” of High-Flow Nasal Cannula Risk: A Scoping Review All risks fell under 8 categories: deterioration, death, device-related events, delay, disposition, debility, distress, and dysphagia (the “8 D's”).

7. accjournal.org accjournal.org/journal/view.php?doi=10.4266/acc.2021.01571

High-flow nasal cannula for respiratory failure in adult ... HFNC has been successfully used in critically ill patients with several conditions, such as hypoxemic respiratory failure, hypercapneic ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9006190/

Clinical efficacy and safety of high-flow nasal cannula ... This protocol aims to evaluate the clinical efficacy and safety of a high-flow nasal cannula (HFNC) for the treatment of COVID-19 patients with acute ...

9. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-024-05040-9

High flow nasal cannula oxygen therapy versus non-invasive ... The aim of this randomized, open label, non-inferiority trial was to compare treatment failure rates between HFNC and NIV in such patients.