Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients

NCT05456542 | Completed Phase 3

• 1 other identifier: 3480
• Study Type: interventional
• Target: 100
• Locations: 3 countries
• Sites: 5

Brief Summary

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

Conditions

Respiratory Failure

Keywords

Laryngeal Edema, Mechanical Ventilation, Cuff Leak Test

Outcome Measures

Primary Outcomes (2)

• 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).

  30 days

• 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.

  1 Year

Secondary Outcomes (10)

• Proportion of patients with Clinically Significant post-extubation stridor

  within 72 hours of extubation;

• Proportion of patients Reintubation

  within 72 hours of extubation;

• Proportion of patients with Post-extubation stridor

  within 72 hours of extubation

• Proportion of patients with Emergency Surgical Airway

  within 72 hours of extubation

• ICU Mortality

  Within 30 days of Randomization

Study Arms (2)

Intervention - Cuff Leak Test

EXPERIMENTAL

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.

Diagnostic Test: Cuff Leak Test; Drug: Dexamethasone 4mg

Control - No Cuff Leak Test

NO 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.

Interventions

Cuff Leak Test DIAGNOSTIC_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.

Intervention - Cuff Leak Test

Dexamethasone 4mg DRUG

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

Intervention - Cuff Leak Test

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Joseph's Healthcare Hamilton: lead
• Hamilton Academic Health Sciences Organization: collaborator

Study Sites (5)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Brantford General Hospital

Brantford, Ontario, Canada

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Niagara Health System

Saint Catherines, Ontario, L2S 0A9, Canada

Location

Al-Amiri Hospital

Kuwait City, Kuwait

Location

Related Publications (15)

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

  BACKGROUND

• 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.

  PMID: 31326936 BACKGROUND

• 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.

  PMID: 28459708 BACKGROUND

• 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.

  PMID: 27762595 BACKGROUND

• 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.

  PMID: 15469575 BACKGROUND

• 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.

  PMID: 7599812 BACKGROUND

• 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.

  PMID: 21376523 BACKGROUND

• 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.

  PMID: 3371019 BACKGROUND

• 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.

  PMID: 9700126 BACKGROUND

• 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.

  PMID: 23672755 BACKGROUND

• 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.

  PMID: 17398307 BACKGROUND

• 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.

  PMID: 23806246 BACKGROUND

• 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.

  PMID: 20237758 BACKGROUND

• 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.

  PMID: 15101002 BACKGROUND

• 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.

  PMID: 40537229 DERIVED

Related Links

• Trial Website

MeSH Terms

Conditions

Respiratory Insufficiency; Laryngeal Edema

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Laryngeal Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Dr. Kimberley Lewis, MD

  St. Joseph's Healthcare Hamilton

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The Research Coordinator will randomize eligible patients in a 1:1 allocation using undisclosed variable block sizes through a central computer system on REDCap. Randomization algorithm will stratify patients by recruitment site. This is an unblinded study as group allocation will be known. However, outcome adjudicators and the study statistician will be blinded to the group allocation.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, SJHH Staff Intensivist, Assistant Professor

Model Details: Multicentred, national, parallel-group, pragmatic vanguard pilot trial.

Study Record Dates

• First Submitted: May 3, 2022
• First Posted: July 13, 2022
• Study Start: April 5, 2023
• Primary Completion: January 6, 2025
• Study Completion: January 6, 2025
• Last Updated: March 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

KU (1); CA (3); US (1)