NCT06259565

Non-invasive Ventilation and Dexmedetomidine in Critically Ill Adults

Non-invasive Ventilation and Dexmedetomidine in Critically Ill Adults: An International Pragmatic Randomized Controlled Trial (inDEX Trial)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 846 (estimated)
• Sponsor: St. Joseph's Healthcare Hamilton · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Non-Invasive ventilation (NIV) is a life saving intervention for patients with acute respiratory failure (ARF). Some patients are not able to tolerate the NIV intervention and ultimately fail, requiring the use of invasive mechanical ventilation (IMV) and intubation. Sedation may improve a patient's NIV tolerance. However, this practice has not been adopted by intensivists as the risk of over-sedation resulting in respiratory depression, inability to protect the airway, and inadvertent need for intubation are all large deterrents of sedative use in NIV. The Non-invasive Ventilation and Dexmedetomidine in Critically Ill Adults: a Pragmatic Randomized Controlled Trial (inDEX) is looking to evaluate the effectiveness of dexmedetomidine compared to placebo in reducing non-invasive ventilation failures in patients admitted to the hospital with acute respiratory failure.

Detailed description

Acute respiratory failure (ARF) is a common reason for admission to an intensive care unit (ICU). Non-invasive positive pressure ventilation (NIV) is a life-saving intervention for selected patients with ARF. Compared to endotracheal intubation and invasive mechanical ventilation (IMV), NIV is safer, less invasive, preferred by most patients, and is associated with a reduced ICU length of stay (LOS), less pneumonia and mortality, and lower healthcare costs. NIV failure can occur, necessitating IMV. Risk factors associated with NIV failure including intolerance, agitation, and delirium. Sedation is a potential solution for NIV intolerance, however the evidence is sparse and the risk of over-sedation resulting in respiratory depression, inability to protect the airway, and inadvertent need for intubation are all large deterrents. Dexmedetomidine (Dex) is an α2-adrenergic agonist sedative commonly used in IMV that promotes patient wakefulness, has no effect on respiratory drive, has important analgesic properties, and reduces delirium. The investigators hypothesize that Dex, when compared to placebo, reduces NIV failure in hospitalized adults with ARF and agitation or NIV intolerance. Overall Goal: To determine if Dex, compared to placebo, reduces the risk of NIV failure in patients that admitted to hospital with acute respiratory failure and are intolerant of NIV. Target Population: 846 patients will be enrolled into the trial if they meet all the following criteria: 1) ≥18 years old; 2) Receiving any NIV modality for ARF of any etiology; 3) Admitted to ICU, PACU, step-down unit (surgical or medical), or emergency department; 4) Presence of one or more of the following: a) Agitation, b) Patient expresses intolerance or requests removal of NIV secondary to self-reported discomfort, anxiety, or claustrophobia, or c) Other reason that the physician feels the patient is intolerant of NIV or agitated not captured above, or feels that the patient will benefit from sedation (all reasons will be recorded). Methods: The inDEX trial is a pragmatic, international, multi-centred, stratified, randomized, parallel-group, placebo-controlled trial. Patients, investigators, healthcare team, data collectors, outcome assessors, and the statistician will be blinded to trial arms. The trial will maximize external validity by including patients in a range of hospitals across the world. Patients randomized to the experimental arm will receive Dex while those randomized to the control arm will receive placebo. Assessment: The primary outcome is NIV failure. The investigators define NIV failure as the proportion that require intubation or have died at 28 days.

Conditions

• Non-Invasive Ventilation

Interventions

Type	Name	Description
DRUG	Dexmedetomidine	Dexmedetomidine (Dex) is an α2-adrenergic agonist sedative commonly used in invasive mechanical ventilation (IMV) that promotes patient wakefulness, has no effect on respiratory drive, has important analgesic properties, and reduces delirium
OTHER	Placebo Control	Those in the control group will receive a placebo that is identical in colour and packaging and at equal volume to the intervention group. Each bag of placebo contains 100mL of 0.9% sodium chloride and labeled as per Health Canada guidance for labelling pharmaceutical drugs for use in humans

Timeline

• Start date: 2025-07-29
• Primary completion: 2029-12-31
• Completion: 2030-01-31
• First posted: 2024-02-14
• Last updated: 2025-09-10

Locations

6 sites across 1 country: Canada