Tube Size Randomized Trial During Emergency Tracheal Intubation (BREATHE)

The Tube Size Randomized Trial During Emergency Tracheal Intubation

The BREATHE trial is a parallel-group, pragmatic, randomized clinical trial comparing the effectiveness of smaller versus larger endotracheal tubes for mechanical ventilation of critically ill adults at 7 geographically diverse centers. A total of 3,180 critically ill adults undergoing tracheal intubation in the ED or ICU will be enrolled. Enrolled patients will be randomly assigned in a 1:1 ratio to receive either a smaller endotracheal tube (a 6.5 mm endotracheal tube for patients shorter than 64 inches and a 7.0 mm endotracheal for patients at least 64 inches) or a larger endotracheal tube (a 7.5 mm endotracheal tube for patients shorter than 64 inches and a 8.0 mm endotracheal for patients at least 64 inches). Patients will be followed for 6 months after enrollment. The primary outcome will be breathlessness at 6 months. The secondary outcomes will be voice quality and swallowing at 6 months.

Study Overview

• Status: Enrolling by invitation
• Conditions: Acute Respiratory Failure
• Intervention / Treatment: Other: Smaller endotracheal tube; Other: Larger endotracheal tube

Detailed Description

Each year, approximately 1% of the US population (2-3 million adults) experiences critical illness requiring placement of an endotracheal tube. While 60-80% of patients survive, more than half of survivors experience long-term problems with breathing, speaking, or swallowing. Identifying approaches that prevent long-term complications of critical illness is an urgent priority.

For every patient undergoing emergency tracheal intubation, clinicians select the size of endotracheal tube. The size of the endotracheal tube refers to the inner diameter of the tube. Smaller endotracheal tubes commonly used in adults have a diameter of 6.5 mm to 7.0 mm. Larger endotracheal tubes commonly used in adults have a diameter of 7.5 mm to 8.0 mm.

In current clinical care, some clinicians routinely use smaller endotracheal tubes while others routinely use larger endotracheal tubes. In a cohort of 2,652 patients enrolled in three recent trials conducted by our Pragmatic Critical Care Research Group (PCCRG), clinicians used a smaller endotracheal tube for 44.5% of patients and a larger endotracheal tube for 55.5%. While height and sex are the primary determinants of the diameter of a patient's trachea, these variables explain only 12% of the variation in the size of endotracheal tube clinicians use in current clinical care. This suggests that selection of endotracheal tube size in clinical practice is not "personalized" to the characteristics of the patient, but instead varies based on factors like the specialty of the clinician, the practice patterns of the hospital, and the region of the country.

Whether using a smaller vs larger endotracheal tube affects any patient outcome is unknown. Some experts have hypothesized that use of larger endotracheal tubes may cause acute injury to the larynx, which for some patients could progress to permanent scarring, impairing breathing, speaking, and swallowing. Thus, some experts currently recommend using smaller endotracheal tubes. Other experts hypothesize that the use of larger endotracheal tubes may reduce resistance to gas flow, reducing patients' work of breathing during spontaneous breathing trials, and making it easier to pass suction catheters, obtain diagnostic samples, and clear secretions. Such experts, therefore, currently recommend using larger endotracheal tubes in hopes that doing so might shorten the duration of invasive mechanical ventilation or even decrease the risk of death during critical illness. No randomized trials have ever compared smaller versus larger endotracheal tube sizes among critically ill adults. Only one observational study has evaluated the effect of endotracheal tube size on outcomes of critical illness. It suggested that smaller endotracheal tubes had no effect on survival to hospital discharge but could not exclude the possibility that endotracheal tube size might affect the duration of invasive mechanical ventilation. The study prompted published responses highlighting the lack of long-term outcomes and the biases inherent to observational studies, noting that the effects of smaller versus larger endotracheal tubes could only be proven with a randomized trial.

Because millions of critically ill adults receive either a smaller or larger endotracheal tube during tracheal intubation in an ED or ICU each year, and no prior randomized trial has evaluated the effect of endotracheal tube size on long-term outcomes (breathing, speaking, and swallowing) or short-term outcomes (duration of invasive mechanical ventilation and survival), a multicenter randomized trial is needed.

• Study Type: Interventional
• Enrollment (Estimated): 3180
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Hospital
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center
    • Denver, Colorado, United States, 80045
      • University of Colorado-Denver
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Atrium Health Wake Forest Baptist
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient is undergoing orotracheal intubation with an endotracheal tube in a participating unit
• Planned operator is a clinician expected to routinely perform tracheal intubation in the participating unit

Exclusion Criteria:

• Patient is known to be less than 18 years old
• Patient is known to be pregnant
• Patient is known to be a prisoner
• Use of an endotracheal tube with subglottic suction is planned
• Operator has determined that use of a smaller endotracheal tube or a larger endotracheal tube is required or contraindicated for the optimal care of the patient
• Immediate need for tracheal intubation precludes safe performance of study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Smaller Endotracheal Tube Group; For patients assigned to the smaller endotracheal tube group, the operator will place a smaller endotracheal tube, as defined below: Inner diameter 7.0 mm (for patients with a height ≥ 64 inches); Inner diameter 6.5 mm (for patients with a height < 64 inches)	Other: Smaller endotracheal tube; Inner diameter 7.0 mm (for patients with a height ≥ 64 inches); Inner diameter 6.5 mm (for patients with a height < 64 inches)
Active Comparator: Larger Endotracheal Tube Group; For patients assigned to the larger endotracheal tube group, the operator will place a larger endotracheal tube, as defined below: Inner diameter 8.0 mm (for patients with a height ≥ 64 inches); Inner diameter 7.5 mm (for patients with a height < 64 inches)	Other: Larger endotracheal tube; Inner diameter 8.0 mm (for patients with a height ≥ 64 inches); Inner diameter 7.5 mm (for patients with a height < 64 inches)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breathlessness at 6 months after intubation	Primary Effectiveness Outcome: Breathlessness will be measured using the Clinical COPD Questionnaire (CCQ). Scores range from 0 (least severe) to 6 (most severe).	At 6 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-free days in the first 28 days	Primary Safety Outcome: The number of days alive and free of invasive mechanical ventilation from enrollment to 28 days after enrollment.	From enrollment to 28 days after enrollment
All-cause, in-hospital mortality by 28 days	Primary Safety Outcome: Death from any cause from enrollment to 28 days after enrollment, censored at hospital discharge.	From enrollment to 28 days after enrollment
Voice impairment at 6 months after intubation	Secondary Effectiveness Outcome: voice impairment at 6 months after enrollment as measured using the Voice Handicap Index (VHI) survey. Scores range from 0 (least severe) to 40 (most severe).	At 6 months after enrollment
Swallowing impairment at 6 months after intubation	Secondary Effectiveness Outcome: Swallowing impairment at 6 months after enrollmnet as measured using the EAT-10 survey. Scores range from 0 (least severe) to 40 (most severe).	At 6 months after enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful intubation on the first attempt.	Successful intubation on the first attempt is defined as placement of an endotracheal tube in the trachea with a single insertion of a laryngoscope blade into the mouth and EITHER a single insertion of an endotracheal tube into the mouth OR a single insertion of a bougie into the mouth followed by a single insertion of an endotracheal tube over the bougie into the mouth.	Duration of placement of the endotracheal tube, an average duration of two minutes
Number of laryngoscopy attempts		Duration of placement of the endotracheal tube, an average duration of two minutes
Number of attempts to cannulate the trachea with a bougie		Duration of placement of the endotracheal tube, an average duration of two minutes
Number of attempts to cannulate the trachea with an endotracheal tube		Duration of placement of the endotracheal tube, an average duration of two minutes
Time from initiation of laryngoscopy to intubation of the trachea	Time from initiation of laryngoscopy to intubation of the trachea in seconds	Duration of placement of the endotracheal tube, an average of 60 seconds
Severe hypoxemia	Lowest oxygen saturation <80%	During procedure (between induction and 2 minutes after tracheal intubation).
Agitation	As measured by the occurrence of a Richmond Agitation-Sedation Scale (RASS) ≥ +2	From intubation to 7 days after enrollment
Delirium	As measured by the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)	From intubation to 7 days after enrollment
Tracheostomy	Occurence of a tracheostomy procedure.	From intubation to 28 days after enrollment
Percutaneous gastrostomy tube placement	Occurence of a gastrostomy tube placement.	From intubation to 28 days after enrollment
Endotracheal tube exchange	Exchange of the endotracheal tube for any reason during the index course of invasive mechanical ventilation	From intubation to 28 days after enrollment
Reintubation within 72 hours of extubation from the index course of invasive mechanical ventilation	Any placement of an endotracheal tube in the trachea (e.g., endotracheal tube, tracheostomy) between extubation from the index course of invasive mechanical ventilation and 72 hours following extubation, excluding reintubations for the purpose of a procedure that lasts <24 hours.	Within 72 hours of extubation
Ventilator associated pneumonia during the index course of invasive mechanical ventilation	New lung infiltrate plus clinical evidence that the infiltrate is of an infectious origin, which include the new onset of fever, purulent sputum, leukocytosis, and decline in oxygenation, beginning > 48 hours after enrollment.	From intubation to 28 days after enrollment
ICU-free days in the 28 days after enrollment		From intubation to 28 days after enrollment
Hospital-free days in the 28 days after enrollment		From intubation to 28 days after enrollment
All-location mortality by 28 days		At 28 days after enrollment
All-cause, all-location mortality by 6 months		At 6 months after enrollment
Prescence of a tracheostomy at 6 months		At 6 months after enrollment
Cough at 6 months	As measured by the Cough Severity Index. Scores range from 0 (no cough) to 40 (severe cough).	At 6 months after enrollment
Throat pain at 6 months	As measured by the Numeric Rating Scale. Scores range from 0 (no pain) to 10 (most severe pain).	At 6 months after enrollment
Voice quality at 6 months	As measured by the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V). Scores range from 0 (mildly deviant) to 100 (severely deviant).	At 6 months after enrollment
Quality of life at 6 months	As measured by the EQ-5D-5L health-related quality of life measure. Scores range from 0 (worst health) to 100 (best health).	At 6 months after enrollment
Anxiety at 6 months	As measured by the General Anxiety Disorder-7 (GAD-7). Scores range from 0 (least severe) to 21 (most severe).	At 6 months after enrollment
Depression at 6 months	As measured by the Patient Health Questionnaire-9. Scores range from 0 (not at all) to 27 (nearly every day).	At 6 months after enrollment
Employment at 6 months	As measured by the OACIS Employment Questionnaire.	At 6 months after enrollment

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: Patient-Centered Outcomes Research Institute

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: April 7, 2025
• First Submitted That Met QC Criteria: April 14, 2025
• First Posted (Actual): April 22, 2025

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: critical illness; tracheal intubation; emergency airway management
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Critical Illness
• Other Study ID Numbers: 250125

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

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