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Respiratory FailurePhase 3COSMICNCT05456542

Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients

A Phase 3 study testing Cuff Leak Test and Dexamethasone 4mg in people with Respiratory Failure, run by St. Joseph's Healthcare Hamilton at 5 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The COSMIC trial will be a multicentred, national, parallel-group, pragmatic vanguard pilot trial. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Respiratory Failure
What is being tested?
Cuff Leak Test and Dexamethasone 4mg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
5 sitesin 3 countries
Study dates
5 Apr 2023to 6 Jan 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥18 yrs. of age
  • Mechanically ventilated in the ICU \
  • An order to extubate has been provided by the treating physician
  • Meet at least 1 criteria for risk factors for Laryngeal Edema(LE):
  • Criteria 1
  • Intubated for >5 days
Show all 21Show fewer
  • Criteria 2 *must fulfill category 1 and ≥1 risk factor in category 2
  • Category 1
  • Intubated for >48 hours
  • Category 2
  • An unplanned extubation event within the last week
  • Airway trauma secondary to an endotracheal intubation during the past week defined as one of the following:
  • More than one attempt at direct laryngoscopy
  • More than one attempt to pass the ETT
  • Charted as a traumatic intubation
  • A body mass index of >30kg/m2
  • An endotracheal tube greater than 8mm in a man or 7mm in a woman
  • A total positive cumulative fluid balance of at least >1500ml/d x # of days admitted to ICU (eg. If admitted for 4 days, the patient will meet this criterion if they are 6L positive during their length of ICU admission)
  • Physician concern about possible laryngeal edema for a reason not previously listed above. For example:
  • Prone or Trendelenburg position in a recent operation
  • Agitation defined as a RASS of 3+ or more or a SAS of 6 or more that may result in airway injury

Who cannot join

  • Palliative care plan or plan of care does not include re-intubation, Decision to withdraw life support, or no plan for re-intubation
  • Known pregnancy: Current pregnancy or up to and including 7 days postpartum
  • Patients with highly suspected laryngeal injury: Burn patients, smoke inhalation injuries, blunt or penetrating trauma of the neck and airway, recent head and neck surgeries, and patients admitted with airway edema
  • Known pre-existing tracheolaryngeal abnormalities: Vocal cord paralysis, tracheolaryngeal neoplasm, tracheomalasia, tracheolaryngeal stenosis, or previous head and neck surgeries
  • Mechanical ventilation via a tracheostomy
  • High dose steroids administered within the previous 72h (Prednisone 1mg/kg oral equivalent)
  • The ICU physician believes the patient should have a CLT performed
  • Patient had a failed CLT in the previous 24 hours

Trial locations and contacts

5 sites in 3 countries.

5 sites in 3 countries

Canada3 sites

  • Brantford General Hospital

    Brantford, Ontario

  • St. Joseph's Healthcare Hamilton

    Hamilton, Ontario, L8N 4A6

  • Niagara Health System

    Saint Catherines, Ontario, L2S 0A9

Other trials in Canada

United States1 site

  • The University of Texas Health Science Center at Houston

    Houston, Texas, 77030

Other trials in United States

Kuwait1 site

  • Al-Amiri Hospital

    Kuwait City

Other trials in Kuwait

About this study

Official title: Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients (COSMIC): A Pilot Randomized Controlled Trial

The COSMIC trial will be a multicentred, national, parallel-group, pragmatic vanguard pilot trial.

Read the detailed description

The COSMIC trial will be a multicentred, national, parallel-group, pragmatic vanguard pilot trial in adults (≥18 years) who are mechanically ventilated in the ICU with risk factors for LE and an order to extubate has been provided by the treating physician.

The aims of this study are to assess:

  1. Protocol adherence
  2. Recruitment rates
  3. Secondary clinical outcomes will be collected, and if feasibility criteria are met, ultimately used in the powered trial pending no major protocol adjustments (otherwise will be reported as cohort data).
Being tested
Cuff Leak Test, Dexamethasone 4mg
Keywords
Laryngeal Edema, Mechanical Ventilation, Cuff Leak Test
Medical subject headings
Respiratory Insufficiency, Laryngeal Edema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cuff Leak TestDiagnostic test

    Clinicians perform the cuff leak test (CLT) to help optimize extubation. The test requires deflation of the cuff at the end of the endotracheal tube (ETT) and auscultation for air passing around the ETT. If air movement is not audible on auscultation (a failed CLT) there is a potential presence of laryngeal edema (LE) that may cause post-extubation airway obstruction.

  • Dexamethasone 4mgDrug

    Dexamethasone, will be administered to those patients who fail the CLT in the intervention arm (4mg intravenous every 6 hours for 12-24 hours). Dexamethasone belongs to a class of drugs known as corticosteroids

Study groups in NCT05456542
Study groupRoleWhat they receive
Intervention - Cuff Leak TestExperimentalA 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.
Receives: Diagnostic Test: Cuff Leak Test; Drug: Dexamethasone 4mg
Control - No Cuff Leak TestNo interventionIn 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Protocol Adherence

    Define a successful adherence rate as ≥75%. We will calculate the adherence as the proportion of patients that are assigned to the intervention arm following the appropriate treatment algorithm and those assigned to the control arm being extubated without a cuff leak test. As this pilot trial is ongoing, we will review adherence monthly and investigate the reasons for compliance failure. We will investigate all reasons for failure to follow the treatment algorithm in the intervention arm, failure to extubate after a patient passes a CLT in the intervention arm, or failure to extubate immediately after randomization in the control arm and report them as a protocol violation. The RC will review the RT's charting and the medication profile to determine actual compliance. RC will record all reasons for non-compliance using distinguishing clinical reasons (eg, palliation, death, consent withdrawal and errors).

    Measured: 30 days

  2. Recruitment Rate

    Define a successful recruitment rate as enrolling three patients per centre per month over the duration of the trial. While the pilot trial is ongoing, steering committee will review recruitment weekly and the screening records monthly. If applicable, we will address barriers to enrolment to maximise recruitment. The recruitment metric will be measured and interpreted at the end of the pilot trial by calculating the mean number of recruited patients per active screening month.

    Measured: 1 Year

Secondary outcomes (10)

  1. Proportion of patients with Clinically Significant post-extubation stridor

    Defined as the presence of an inspiratory noise following extubation that requires medical intervention such as racemic epinephrine

    Measured: within 72 hours of extubation;

  2. Proportion of patients Reintubation

    Re insertion of an endotracheal tube to maintain an airway within 72 hours for any reason (reasons for reintubation will be captured)

    Measured: within 72 hours of extubation;

  3. Proportion of patients with Post-extubation stridor

    Defined as the presence of an inspiratory noise following extubation.

    Measured: within 72 hours of extubation

  4. Proportion of patients with Emergency Surgical Airway

    A procedure performed to secure the airway in patients with upper airway obstruction who could not be managed with intubation or mechanical ventilation.

    Measured: within 72 hours of extubation

  5. ICU Mortality

    Death during Intensive Care Unit admission

    Measured: Within 30 days of Randomization

  6. Hospital Mortality

    Death during Intensive Care Unit admission

    Measured: Within 30 days of Randomization

  7. Ventilator Free Days

    Number of days alive and free of mechanical ventilation.

    Measured: Within 30 Days of Randomization

  8. ICU Length of Stay

    Number of days admitted to the ICU

    Measured: Within 30 days of Randomization

  9. Length of Stay

    Number of days admitted to hospital

    Measured: Within 30 days of Randomization

  10. Proportion of patients with Ventilator Associated Pneumonia

    Pneumonia occurring more than 48 h after patients have been intubated and received mechanical ventilation.

    Measured: 30 Days from Randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2022
  2. Study start5 Apr 2023
  3. Primary completion6 Jan 2025
  4. Study completion6 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multicentred, national, parallel-group, pragmatic vanguard pilot trial.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05456542
Sponsor's protocol ID
3480
Acronym
COSMIC
Status last verified
Jan 2025
First submitted
3 May 2022
Last updated
10 Mar 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Sandoz Canada Inc. Prescribing Information - Dexamethasone Sodium Phosphate Injection USP (4 mg/mL and 10 mg/mL Sterile Corticosteroid.

  • Lewis K, Culgin S, Jaeschke R, Perri D, Marchildon C, Hassall K, Piraino T, Thabane L, Almubarak Y, Alshahrani MS, Rochwerg B, Baw B, Szczeklik W, Karachi T, Alhazzani W; GUIDE Group. Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients (COMIC): a pilot randomised controlled trial protocol. BMJ Open. 2019 Jul 19;9(7):e029394. doi: 10.1136/bmjopen-2019-029394.

    PubMed 31326936

  • Alhazzani W, Guyatt G, Alshahrani M, Deane AM, Marshall JC, Hall R, Muscedere J, English SW, Lauzier F, Thabane L, Arabi YM, Karachi T, Rochwerg B, Finfer S, Daneman N, Alshamsi F, Zytaruk N, Heel-Ansdell D, Cook D; Canadian Critical Care Trials Group. Withholding Pantoprazole for Stress Ulcer Prophylaxis in Critically Ill Patients: A Pilot Randomized Clinical Trial and Meta-Analysis. Crit Care Med. 2017 Jul;45(7):1121-1129. doi: 10.1097/CCM.0000000000002461.

    PubMed 28459708

  • Girard TD, Alhazzani W, Kress JP, Ouellette DR, Schmidt GA, Truwit JD, Burns SM, Epstein SK, Esteban A, Fan E, Ferrer M, Fraser GL, Gong MN, Hough CL, Mehta S, Nanchal R, Patel S, Pawlik AJ, Schweickert WD, Sessler CN, Strom T, Wilson KC, Morris PE; ATS/CHEST Ad Hoc Committee on Liberation from Mechanical Ventilation in Adults. An Official American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults. Rehabilitation Protocols, Ventilator Liberation Protocols, and Cuff Leak Tests. Am J Respir Crit Care Med. 2017 Jan 1;195(1):120-133. doi: 10.1164/rccm.201610-2075ST.

    PubMed 27762595

  • Seymour CW, Martinez A, Christie JD, Fuchs BD. The outcome of extubation failure in a community hospital intensive care unit: a cohort study. Crit Care. 2004 Oct;8(5):R322-7. doi: 10.1186/cc2913. Epub 2004 Jul 20.

    PubMed 15469575

  • Torres A, Gatell JM, Aznar E, el-Ebiary M, Puig de la Bellacasa J, Gonzalez J, Ferrer M, Rodriguez-Roisin R. Re-intubation increases the risk of nosocomial pneumonia in patients needing mechanical ventilation. Am J Respir Crit Care Med. 1995 Jul;152(1):137-41. doi: 10.1164/ajrccm.152.1.7599812.

    PubMed 7599812

  • Frutos-Vivar F, Esteban A, Apezteguia C, Gonzalez M, Arabi Y, Restrepo MI, Gordo F, Santos C, Alhashemi JA, Perez F, Penuelas O, Anzueto A. Outcome of reintubated patients after scheduled extubation. J Crit Care. 2011 Oct;26(5):502-509. doi: 10.1016/j.jcrc.2010.12.015. Epub 2011 Mar 3.

    PubMed 21376523

  • Demling RH, Read T, Lind LJ, Flanagan HL. Incidence and morbidity of extubation failure in surgical intensive care patients. Crit Care Med. 1988 Jun;16(6):573-7. doi: 10.1097/00003246-198806000-00001.

    PubMed 3371019

  • Epstein SK, Ciubotaru RL. Independent effects of etiology of failure and time to reintubation on outcome for patients failing extubation. Am J Respir Crit Care Med. 1998 Aug;158(2):489-93. doi: 10.1164/ajrccm.158.2.9711045.

    PubMed 9700126

  • Zhou T, Zhang HP, Chen WW, Xiong ZY, Fan T, Fu JJ, Wang L, Wang G. Cuff-leak test for predicting postextubation airway complications: a systematic review. J Evid Based Med. 2011 Nov;4(4):242-54. doi: 10.1111/j.1756-5391.2011.01160.x.

    PubMed 23672755

  • Francois B, Bellissant E, Gissot V, Desachy A, Normand S, Boulain T, Brenet O, Preux PM, Vignon P; Association des Reanimateurs du Centre-Ouest (ARCO). 12-h pretreatment with methylprednisolone versus placebo for prevention of postextubation laryngeal oedema: a randomised double-blind trial. Lancet. 2007 Mar 31;369(9567):1083-9. doi: 10.1016/S0140-6736(07)60526-1.

    PubMed 17398307

  • Sutherasan Y, Theerawit P, Hongphanut T, Kiatboonsri C, Kiatboonsri S. Predicting laryngeal edema in intubated patients by portable intensive care unit ultrasound. J Crit Care. 2013 Oct;28(5):675-80. doi: 10.1016/j.jcrc.2013.05.011. Epub 2013 Jun 24.

    PubMed 23806246

  • Tadie JM, Behm E, Lecuyer L, Benhmamed R, Hans S, Brasnu D, Diehl JL, Fagon JY, Guerot E. Post-intubation laryngeal injuries and extubation failure: a fiberoptic endoscopic study. Intensive Care Med. 2010 Jun;36(6):991-8. doi: 10.1007/s00134-010-1847-z. Epub 2010 Mar 18.

    PubMed 20237758

  • Maury E, Guglielminotti J, Alzieu M, Qureshi T, Guidet B, Offenstadt G. How to identify patients with no risk for postextubation stridor? J Crit Care. 2004 Mar;19(1):23-8. doi: 10.1016/j.jcrc.2004.02.005.

    PubMed 15101002

  • Estrada J, Armanious I, Perri D, Cook DJ, Duan EH, Bosma K, Hassall K, Marchildon C, Mehta S, Jaeschke R, Piraino T, Carayannopoulos KL, Alhazzani W, Lewis K. Cuff leak test and airway obstruction in mechanically ventilated ICU patients (COSMIC): a pilot feasibility randomized controlled trial protocol. BMJ Open. 2025 Jun 19;15(6):e096053. doi: 10.1136/bmjopen-2024-096053.

    PubMed 40537229

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cuff Leak Test and Dexamethasone 4mg in people with Respiratory Failure, run by St. Joseph's Healthcare Hamilton at 5 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Canada, United States, Kuwait. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Protocol Adherence (time frame: 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05456542, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2025.

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