Preventing Hypoxemia With Manual Ventilation During Endotracheal Intubation (PreVent) Trial

Study Overview
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Brief Summary
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Complications are common during endotracheal intubation of critically ill adults. Manual ventilation between induction and intubation (bag-valve-mask ventilation) has been proposed as a means of preventing hypoxemia, the most common complication of intubation outside the operating room. Safety and efficacy data, however, are lacking. PreVent is a randomized trial comparing manual ventilation between induction and laryngoscopy to no manual ventilation between induction an laryngoscopy during endotracheal intubation of critically ill adults. The primary efficacy endpoint will be the lowest arterial oxygen saturation. The primary safety endpoints will be the lowest oxygen saturation, highest fraction of inspired oxygen, and highest positive end-expiratory pressure in the 24 hours after the procedure.

Detailed Description
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PreVent is a prospective, parallel-group, pragmatic, randomized trial comparing manual ventilation between induction and laryngoscopy to no manual ventilation between induction an laryngoscopy during endotracheal intubation of critically ill adults. The primary aim of the PreVent trial is to compare the effect of manual ventilation between induction and intubation versus no manual ventilation on the lowest arterial oxygen saturation experienced by critically ill adults undergoing endotracheal intubation. The PreVent trial is anticipated to begin enrollment in January 2017 and will enroll adults undergoing endotracheal intubation with sedation and/or neuromuscular blockade in participating units. Patients will be randomized 1:1 to manual ventilation versus no manual ventilation. In the manual ventilation group, manual ventilation using a bag-valve-mask will be provided from the time of induction until the time of endotracheal intubation, except during laryngoscopy. In the no manual ventilation group, no manual ventilation will be provided between induction and endotracheal intubation, except for the treatment of hypoxemia. The primary efficacy endpoint will be the lowest arterial oxygen saturation during the procedure. The primary safety endpoints will be the lowest oxygen saturation, highest fraction of inspired oxygen, and highest positive end expiratory pressure in the 24 hours after intubation. Conduct of the trial will be overseen by a Data Safety Monitoring Board. An interim analysis will be performed after the enrollment of 175 patients. The analysis of the trial will be conducted in accordance with a pre-specified statistical analysis plan made publicly available prior to the conclusion of enrollment. The initial planned enrollment of 350 patients was increased by the Data and Safety Monitoring Board at the interim analysis to a final planned enrollment of 400 patients.

Official Title
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Preventing Hypoxemia With Manual Ventilation During Endotracheal Intubation (PreVent) Trial

Conditions
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Respiratory Failure, Respiratory Failure With Hypoxia, Endotracheal Intubation

Intervention / Treatment
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* Other: Manual Ventilation
* Other: No Manual Ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is located in a participating unit Planned procedure is endotracheal intubation Planned operator is a provider expected to routinely perform endotracheal intubation in the participating unit Administration of sedation and/or neuromuscular blockade is planned Age ≥ 18 years old Exclusion Criteria: Urgency of intubation precludes safe performance of study procedures Operator feels a specific approach to ventilation between induction and intubation is required Pregnant women Prisoners

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Manual Ventilation<br>Beginning after the administration of sedation/neuromuscular blockade, manual ventilation will be provided by bag-valve-mask until the initiation of laryngoscopy. In patients requiring more than one attempt at laryngoscopy, bag-valve-mask ventilation will resume between laryngoscopy attempts. | Other: Manual Ventilation<br>* Beginning after the administration of sedation/neuromuscular blockade, manual ventilation will be provided by bag-valve-mask until the initiation of laryngoscopy. In patients requiring more than one attempt at laryngoscopy, bag-valve-mask ventilation will resume between laryngoscopy attempts.<br>* Other names: Bag-valve-mask ventilation;|
| Active Comparator: No Manual Ventilation<br>Between the administration of sedation/neuromuscular blockade and intubation, ventilation will not be provided unless the patient experiences an arterial oxygen saturation less than 90%. For patients who experience an oxygen saturation less than 90% after induction, bag-valve-mask ventilation may be provided. | Other: No Manual Ventilation<br>* Between the administration of sedation/neuromuscular blockade and intubation, ventilation will not be provided unless the patient experiences an arterial oxygen saturation less than 90%. For patients who experience an oxygen saturation less than 90% after induction, bag-valve-mask ventilation may be provided.<br>* Other names: Apnea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lowest arterial oxygen saturation | The lowest arterial oxygen saturation measured by continuous pulse oximetry (SpO2) between induction and 2 minutes after completion of the airway management procedure. | Induction to 2 minutes after completion of the airway management procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of lowest oxygen saturation less than 90% | Incidence of lowest oxygen saturation less than 90% in the time from induction to 2 minutes after completion of the airway management procedure. | Induction to 2 minutes after completion of the airway management procedure | 
| Incidence of lowest oxygen saturation less than 80% | Incidence of lowest oxygen saturation less than 80% in the time from induction to 2 minutes after completion of the airway management procedure. | Induction to 2 minutes after completion of the airway management procedure | 
| Change in saturation from induction to lowest oxygen saturation | Change in saturation from induction to lowest oxygen saturation within 2 minutes after completion of the airway management procedure. | Induction to 2 minutes after completion of the airway management procedure | 
| Incidence of desaturation | Incidence of desaturation as defined by a decrease in oxygen saturation of greater than 3% from induction to lowest oxygen saturation within 2 minutes after completion of the airway management procedure. | Induction to 2 minutes after completion of the airway management procedure | 
| Lowest oxygen saturation in the 24 hours after intubation. |  | 24 hours after intubation | 
| Highest fraction of inspired oxygen in the 24 hours after intubation. |  | 24 hours after intubation | 
| Highest positive end expiratory pressure in the 24 hours after intubation. |  | 24 hours after intubation | 
| Lowest oxygen saturation, highest fraction of inspired oxygen, and highest positive end expiratory pressure from 0-1, 1-6, and 6- 24 hours after intubation. | Lowest oxygen saturation, highest fraction of inspired oxygen, and highest positive end expiratory pressure from 0-1, 1-6, and 6- 24 hours after intubation. | 24 hours after intubation | 
| Operator-reported pulmonary aspiration | Visualization of oropharyngeal or gastric contents in the pharynx, larynx, or trachea between induction and completion of airway management. | Induction to 2 minutes after completion of the airway management procedure | 
| New infiltrate on chest imaging in the 48 hours after intubation | Determination of new infiltrate will be made by two blinded experts (pulmonary/critical care attendings or fellows) with adjudication by a third expert in the case of discordant results | 48 hours after intubation | 
| Operator-reported pulmonary aspiration, new chest x-ray infiltrate, OR lowest oxygen saturation < 80% (composite outcome) |  | 48 hours after intubation | 
| New pneumothorax or pneumomediastinum on chest imaging in the 24 hours after intubation |  | 24 hours after intubation | 
| Incidence of esophageal intubation |  | Induction to 2 minutes after completion of the airway management procedure | 
| Lowest systolic blood pressure (peri-procedural) | Lowest systolic blood pressure between induction and two minutes after completion of the airway management procedure | Induction to 2 minutes after completion of the airway management procedure | 
| New systolic blood pressure < 65 mmHg or new need for vasopressor | New systolic blood pressure < 65 mmHg or new need for vasopressor between medication administration and 2 minutes following successful placement of an endotracheal tube | Induction to 2 minutes after completion of the airway management procedure | 
| Cardiac arrest within one hour of intubation |  | One hour after intubation. | 
| Death within one hour of intubation |  | One hour after intubation | 
| Cormack-Lehane grade of glottic view |  | Induction to 2 minutes after completion of the airway management procedure | 
| Operator-assessed difficulty of intubation |  | Induction to 2 minutes after completion of the airway management procedure | 
| Incidence of successful intubation on the first laryngoscopy attempt |  | Induction to 2 minutes after completion of the airway management procedure | 
| Number of laryngoscopy attempts |  | Induction to 2 minutes after completion of the airway management procedure | 
| Time from induction to successful intubation |  | Induction to 2 minutes after completion of the airway management procedure | 
| Need for additional airway equipment or a second operator |  | Induction to 2 minutes after completion of the airway management procedure | 
| In-hospital mortality |  | 28 days | 
| Ventilator-free days | Ventilator-free days to day 28 will be defined as the number of days alive and with unassisted breathing to day 28 after enrollment, assuming a patient survives for at least two consecutive calendar days after initiating unassisted breathing and remains free of assisted breathing. If a patient returns to assisted breathing and subsequently achieves unassisted breathing prior to day 28, VFD will be counted from the end of the last period of assisted breathing to day 28. If the patient is receiving assisted ventilation at day 28 or dies prior to day 28, VFD will be 0. If a patient is discharged while receiving assisted ventilation, VFD will be 0. All data will be censored at the first of hospital discharge or 28 days. | 28 days | 
| Intensive care unit-free days | ICU-free days to 28 days after enrollment will be defined as the number of days alive and not admitted to an intensive care unit service after the patient's final discharge from the intensive care unit in that hospitalization before 28 days. Patients who are never discharged from the intensive care unit will receive a value of 0. Patients who die before day 28 will receive a value of 0. For patients who return to an ICU and are subsequently discharged prior to day 28, ICU-free days will be counted from the date of final ICU discharge. All data will be censored at the first of hospital discharge or 28 days. | 28 days |