Dexamethasone + Cuff Leak Test for Airway Blockage in Mechanically Ventilated ICU Patients

(COSMIC Trial)

No longer recruiting at 8 trial locations

Overseen By Irene Armanious

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: St. Joseph's Healthcare Hamilton

Must not be taking: High dose steroids

Disqualifiers: Palliative care, Pregnancy, Laryngeal injury, Tracheolaryngeal abnormalities, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12-24 hours per extubation attempt

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a treatment approach using a Cuff Leak Test can prevent airway blockage in ICU patients on breathing machines. The treatment involves checking for air leaks around the breathing tube; if a blockage is detected, patients receive dexamethasone (a corticosteroid) to reduce swelling before attempting to remove the tube again. The trial compares this method to the standard approach, where the tube is removed without the test or drug. This trial may suit ICU patients who have been on a ventilator for more than five days and are at risk for throat swelling or airway blockage. As a Phase 3 trial, it represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on high-dose steroids, you may not be eligible to participate.

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

Research has shown that the Cuff Leak Test (CLT) is generally safe. This test involves deflating a small balloon on a breathing tube to check if air can move around it, helping to identify throat swelling, which can occur in up to 55% of ventilator patients. The test itself usually doesn't cause any issues.

Dexamethasone, a medication used in this trial, is already employed for other health conditions. Research indicates it can reduce throat swelling after removing a breathing tube. Most patients tolerate it well, and studies suggest it lowers the risk of throat swelling in high-risk patients, with few side effects.

Overall, both the Cuff Leak Test and dexamethasone have demonstrated safety in previous studies, with few adverse events reported. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores whether using a Cuff Leak Test (CLT) combined with dexamethasone can improve the process of extubating ICU patients on mechanical ventilation. Unlike the standard approach where patients are extubated when deemed ready without a CLT, this method adds an extra safety check. The CLT identifies potential airway blockages before removing the breathing tube, and if a blockage is detected, dexamethasone is administered to reduce inflammation, potentially lowering the risk of complications. This protocol aims to offer a more tailored and potentially safer extubation process, which could result in better patient outcomes.

What evidence suggests that the Cuff Leak Test and Dexamethasone could be effective for airway blockage in ICU patients?

In this trial, the cuff leak test (CLT) helps predict airway blockages after removing a breathing tube. The test effectively confirms when no blockage exists, but it might not detect every blockage. Participants in the intervention arm undergo the CLT, and if a blockage appears, dexamethasone—a steroid that reduces swelling—will be administered. This approach aims to improve the chances of successful tube removal by addressing throat swelling. The combination can delay tube removal if a blockage is found, allowing time for the swelling to decrease. Although not perfect, using the CLT with dexamethasone offers a promising method to manage airway blockages in ventilated patients. ^{1 5 6 7 8}

Who Is on the Research Team?

Dr. Kimberley Lewis, MD

Principal Investigator

St. Joseph's Healthcare Hamilton

Are You a Good Fit for This Trial?

Adults over 18 in the ICU on a ventilator with plans to remove it can join. They must have been intubated for more than 5 days or meet other risk factors for throat swelling after extubation. Pregnant women, those with neck injuries, recent surgeries, or severe airway edema are excluded.

Inclusion Criteria

I was intubated for more than 5 days or meet other risk factors for Laryngeal Edema.

I am on a breathing machine in the ICU, but my doctor has ordered it to be removed.

Exclusion Criteria

My care plan does not include being put back on a ventilator or withdrawing life support.

I am on a breathing machine through a hole in my neck.

I have known issues with my voice box or windpipe, including previous surgeries.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a Cuff Leak Test and receive dexamethasone if necessary, with extubation attempts based on test results

12-24 hours per extubation attempt

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after extubation, including assessment of secondary outcomes such as post-extubation stridor and reintubation

72 hours

Extended Follow-up

Participants are monitored for additional outcomes such as ICU and hospital mortality, and ventilator-free days

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Cuff Leak Test
• Dexamethasone 4mg

Trial Overview The COSMIC trial is testing if Dexamethasone and a Cuff Leak Test before taking out a breathing tube can predict and prevent throat blockage in ICU patients. It's conducted across multiple centers and randomly assigns patients to different groups.

How Is the Trial Designed?

Group I: Intervention - Cuff Leak Test Experimental Treatment 2 Interventions

A respiratory therapist will perform a Cuff Leak Test on all patients prior to extubation. If no air leak is auscultated (a failed CLT), extubation will be delayed. During this time, the patient will receive dexamethasone 4mg intravenous every 6 hours for 12-24 hours and the clinical team will be advised to consider optimizing a patient's fluid status through either diuresis or ultrafiltration if the patient has renal failure. After 12-24 hours, and once the clinical team decides the patient is ready for another extubation attempt, the CLT will be repeated. If the patient fails the CLT again, it will be at the discretion of the clinical team how to proceed (i.e. continue steroid administration, and further delay extubation vs immediately extubating despite a failed CLT) (Figure 3). A passed CLT at any time point will result in immediate extubation.

Group II: Control - No Cuff Leak Test Active Control 1 Intervention

In the control group, once the patient is deemed ready for extubation by the clinical team, the patient will be extubated without performing a CLT, without administration of corticosteroids, and without delay.

Who Is Running the Clinical Trial?

St. Joseph's Healthcare Hamilton

Lead Sponsor

Trials

203

Recruited

26,900+

Hamilton Academic Health Sciences Organization

Collaborator

Trials

22

Recruited

5,200+

Published Research Related to This Trial

A survey of 1184 intensivists revealed that 59% rarely or never perform the cuff leak test (CLT) before extubating patients who are not at high risk for laryngeal edema, indicating skepticism about its predictive value for reintubation.

The likelihood of requesting a CLT varies significantly by region and specialty, with intensivists from the Middle East being 2.4 times more likely to use the test compared to those in North America, suggesting that practice patterns are influenced by geographical and training backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cuff leak test in critically ill patients: An international survey of intensivists. Lewis, K., Almubarak, Y., Hylander Møller, M., et al.[2022]

In a study of 30 healthy women taking combined oral contraceptives, the two-day low-dose dexamethasone suppression test (2d-DST) showed significantly lower plasma cortisol levels and fewer unclear or abnormal results compared to the overnight 1-mg dexamethasone suppression test (1-mg DST).

The 2d-DST may be a more reliable screening method for Cushing's syndrome in women on oral contraceptives, as it produced no abnormal results, while the 1-mg DST had 11% abnormal results, suggesting it could reduce false positives in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-day low-dose dexamethasone suppression test more accurate than overnight 1-mg in women taking oral contraceptives. Carton, T., Mathieu, E., Wolff, F., et al.[2022]

The low-dose tetracosactide test (1 microg) shows a strong correlation in cortisol response at 30 and 60 minutes, suggesting it may be a reliable method for diagnosing adrenal insufficiency in traumatic brain injury (TBI) patients.

However, the low-dose and high-dose tests (250 microg) produced discordant results in 43% of cases, and neither test effectively identified patients who would respond to corticosteroid therapy, indicating limitations in their clinical utility for guiding treatment in acute TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose and high-dose synacthen tests and the hemodynamic response to hydrocortisone in acute traumatic brain injury. Wijesurendra, RS., Bernard, F., Outtrim, J., et al.[2021]

The intravenous very low dose dexamethasone suppression test (VLD IV-DST) effectively measures individual glucocorticoid sensitivity across different age groups, with a study involving 87 participants (44 children, 23 adolescents, and 20 adults).

Results showed significant variability in cortisol response to dexamethasone, with median reductions of 44.4% in children, 25.9% in adolescents, and 61.6% in adults, indicating that age influences glucocorticoid sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A very low dose intravenous dexamethasone suppression test as an index of glucocorticoid sensitivity. Faria, CD., Cobra, JF., Sousa E Silva, T., et al.[2019]

In a study involving 524 patients tested 531 times in a cardiovascular ICU, the cuff-leak test was found to be inaccurate for predicting post-extubation complications.

Despite 20 patients having a positive leak test, none experienced issues, while three patients with significant leaks still developed post-extubation stridor, indicating that the test should not be used routinely in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the cuff-leak test in a cardiac surgery population. Engoren, M.[2019]

Quantifying dexamethasone levels in serum samples during the dexamethasone suppression test (DST) significantly improved the test's specificity for diagnosing Cushing syndrome, increasing it from 67.5% to 92.4% while maintaining 100% sensitivity.

The study analyzed 400 serum samples and found that low dexamethasone levels (<1.8 ng/mL) were associated with non-compliance, suggesting that measuring dexamethasone can help identify patients who may not have taken the medication properly, thus reducing false positives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Method-Specific Cortisol and Dexamethasone Thresholds Increase Clinical Specificity of the Dexamethasone Suppression Test for Cushing Syndrome. Vogg, N., Kurlbaum, M., Deutschbein, T., et al.[2022]

In a study of 95 patients requiring percutaneous dilatational tracheostomy after prolonged translaryngeal intubation, 36.8% developed severe laryngeal edema, indicating a significant risk in this population.

The cuff-leak test showed high sensitivity (88.6%) and specificity (90.0%) for predicting severe laryngeal edema, with a threshold of 140 mL indicating potential edema, suggesting it is a useful clinical tool for assessing airway safety before extubation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cuff-leak test is a simple tool to verify severe laryngeal edema in patients undergoing long-term mechanical ventilation. Chung, YH., Chao, TY., Chiu, CT., et al.[2022]

The cuff leak test (CLT) is a simple, reliable, and cost-effective method for predicting the risk of laryngospasm after extubation in patients weaning from mechanical ventilation, based on a systematic review of studies from 1995 to 2007.

The review suggests that the CLT can effectively indicate potential airway obstruction, helping to identify patients at higher risk for extubation failure, thus improving patient safety in the ICU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of the cuff leak test as a factor to predict laryngospasm]. Saback, LM., Vieira, GF., Costa, MD.[2014]

The cuff leak test, which assesses airway obstruction, is more accurate when performed with patients connected to a mechanical ventilator compared to when they are detached, based on a study of 20 intubated patients.

Significant differences in air leak measurements were found between the different testing methods, particularly for patients with shorter intubation times and lower cuff pressures, indicating that these factors may influence test accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cuff leak test preextubation: comparison between three methods in spontaneous ventilation]. Souza, Sda S., Figueiredo, LC., Guedes, CA., et al.[2014]

The COMIC pilot study successfully enrolled 100 mechanically ventilated patients across multiple countries, demonstrating that the cuff leak test (CLT) can be feasibly integrated into clinical decision-making regarding extubation.

While the study met all feasibility criteria, including high recruitment and consent rates, there were no significant differences in reintubation rates or stridor episodes between the intervention and control groups, indicating the need for further research on the CLT's clinical utility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cuff Leak Test and Airway Obstruction in Mechanically Ventilated Intensive Care Unit Patients: A Pilot Randomized Controlled Clinical Trial. Lewis, K., Culgin, S., Jaeschke, R., et al.[2022]

The implementation of an electronic medical record (EMR) protocol significantly improved the correct performance of the cosyntropin stimulation test (CST) for diagnosing adrenal-cortisol insufficiency, increasing accuracy from 16.1% to 53.5%.

This improvement not only enhanced test reliability but also resulted in substantial cost savings of approximately $50,414 for every 100 tests performed, demonstrating the EMR's effectiveness in optimizing medical testing processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced cosyntropin stimulation test performance enabled by electronic medical record. Ben-Shlomo, A., Guzman, J., Mirocha, J.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12182161/

Cuff leak test and airway obstruction in mechanically ... The cuff leak test (CLT) is hypothesised to help optimise extubation by assessing for laryngeal oedema which, if unrecognised and untreated, ...

2. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-020-03358-8

Performance of the cuff leak test in adults in predicting post ... Conclusions. The cuff leak test has excellent specificity but moderate sensitivity for post-extubation airway obstruction. The high specificity ...

3. clinicalview.gehealthcare.com clinicalview.gehealthcare.com/article/using-cuff-leak-test-predict-extubation-success-or-failure

Cuff-Leak Test to Predict Extubation Success or Failure The positive cuff-leak test can, in a high percentage, predict post-extubation airway obstruction. However, due to its low to moderate ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05550220

Study Details | NCT05550220 | A Modified Cuff Leak Test ... The cuff leak test is an effective method for predicting the occurrence of upper airway obstruction in patients with endotracheal intubation after extubation, ...

5. bmjopen.bmj.com bmjopen.bmj.com/content/9/7/e029394

Cuff Leak Test and Airway Obstruction in Mechanically ... Despite the lack of high-quality studies, an absent cuff leak usually results in delayed extubation and exposure to medications aimed at treating airway oedema.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05456542

Study Details | NCT05456542 | Cuff Leak Test and Airway ... A procedure performed to secure the airway in patients with upper airway obstruction who could not be managed with intubation or mechanical ventilation. within ...

7. atsjournals.org atsjournals.org/doi/pdf/10.1513/AnnalsATS.202103-390OC

Cuff Leak Test and Airway Obstruction in Mechanically ... It is anticipated that approximately 4-55% of mechanically ventilated ICU patients will have some degree of laryngeal edema within 24 hours of intubation [2–6].

8. journal.chestnet.org journal.chestnet.org/article/S0012-3692(25)00146-1/abstract

Modified Cuff Leak Test for Predicting the Risk of Reintubation ... Cuff leak test and airway obstruction in mechanically ventilated intensive care unit patients: a pilot randomized controlled clinical trial.