Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients (COSMIC)

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.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Failure
• Intervention / Treatment: Diagnostic test: Cuff Leak Test; Drug: Dexamethasone 4mg

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).

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jose Estrada; Phone Number: 32873 905-522-1155; Email: jestrada@stjosham.on.ca
• Study Contact Backup: Name: Irene Armanious; Phone Number: 32873 905-522-1155; Email: iarmanio@stjosham.on.ca

Study Locations

• Canada
  • Ontario
    • Brantford, Ontario, Canada
      • Recruiting
      • Brantford General Hospital
      • Principal Investigator: Brenda Reeve, MD
      • Contact: Brenda Reeve, MD
    • Hamilton, Ontario, Canada, L8N 4A6
      • Recruiting
      • St. Joseph's Healthcare Hamilton
      • Principal Investigator: Kimberley Lewis, MD
      • Contact: Jose Estrada; Phone Number: 32873 905-522-1155; Email: jestrada@stjosham.on.ca
      • Contact: Irene Armanious; Phone Number: 32873 905-522-1155; Email: iarmanio@stjosham.on.ca
• Kuwait
  • Kuwait City, Kuwait
    • Not yet recruiting
    • AL-Amiri Hospital
    • Principal Investigator: Abdulrahman Al-Fares, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥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
• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention - Cuff Leak Test; 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; 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.; Drug: Dexamethasone 4mg; 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
No Intervention: Control - No Cuff Leak Test; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	within 72 hours of extubation;
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)	within 72 hours of extubation;
Proportion of patients with Post-extubation stridor	Defined as the presence of an inspiratory noise following extubation.	within 72 hours of extubation
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.	within 72 hours of extubation
ICU Mortality	Death during Intensive Care Unit admission	Within 30 days of Randomization
Hospital Mortality	Death during Intensive Care Unit admission	Within 30 days of Randomization
Ventilator Free Days	Number of days alive and free of mechanical ventilation.	Within 30 Days of Randomization
ICU Length of Stay	Number of days admitted to the ICU	Within 30 days of Randomization
Length of Stay	Number of days admitted to hospital	Within 30 days of Randomization
Proportion of patients with Ventilator Associated Pneumonia	Pneumonia occurring more than 48 h after patients have been intubated and received mechanical ventilation.	30 Days from Randomization

Collaborators and Investigators

• Sponsor: St. Joseph's Healthcare Hamilton
• Collaborators: Hamilton Academic Health Sciences Organization
• Investigators: Principal Investigator: Kimberley Lewis, MD, St. Joseph's Healthcare Hamilton

Publications and helpful links

Helpful Links

• Trial Website

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2023
• Primary Completion (Estimated): May 30, 2024
• Study Completion (Estimated): November 30, 2024

Study Registration Dates

• First Submitted: May 3, 2022
• First Submitted That Met QC Criteria: July 12, 2022
• First Posted (Actual): July 13, 2022

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Laryngeal Edema, Mechanical Ventilation, Cuff Leak Test
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Airway Obstruction; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: 3480

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No