Dexmedetomidine to help adults tolerate non-invasive ventilation

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

This trial will test whether giving dexmedetomidine helps adults with acute respiratory failure tolerate non-invasive ventilation and avoid needing a breathing tube.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 846 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: St. Joseph's Healthcare Hamilton (other)
• Locations: 6 sites (Surrey, British Columbia and 5 other locations)
• Trial ID: NCT06259565 on ClinicalTrials.gov

What this trial studies

This is a phase 3, randomized, placebo-controlled trial comparing dexmedetomidine versus placebo in adults receiving non-invasive ventilation (NIV) who are agitated or intolerant of NIV. About 846 participants aged 18 or older will be enrolled at monitored hospital sites and randomized to receive titrated dexmedetomidine or placebo while on NIV. The primary outcome is NIV failure leading to invasive mechanical ventilation (intubation); secondary outcomes include measures of tolerance, delirium, and ICU length of stay. The trial tests whether dexmedetomidine's sedative and anti-delirium properties, with minimal respiratory depression, reduce the need for intubation.

Who should consider this trial

Good fit: Adults (≥18) admitted to monitored hospital areas who are receiving any NIV for acute respiratory failure and who show agitation or express intolerance to NIV despite optimization are the intended candidates.

Not a fit: Patients who are already tolerating NIV, require immediate intubation, or have contraindications to dexmedetomidine (for example severe bradycardia or conduction abnormalities) are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the intervention could reduce the number of patients on NIV who require intubation and its associated complications.

How similar studies have performed: Smaller studies and observational reports suggest dexmedetomidine can improve NIV tolerance and preserve respiratory drive, but high-quality randomized evidence is limited to date.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years
2. Patient receiving any NIV modality for acute respiratory failure of any etiology
3. Admitted to ICU, PACU, step-down unit (surgical or medical), or emergency department(with planned admission to a monitored setting) or equivalent unit where hemodynamics and respiratory status can be monitored, and NIV is permitted; and
4. Presence of one or more of the following after optimized NIV treatment:

   1. Agitation (Defined as a Richmond Agitation and Sedation Scale \[RASS\] score of ≥+2 or a Riker Sedation-Agitation Scale \[SAS\] score of ≥5) (Appendix 1 Table 2 and Table 3)
   2. Patient expresses intolerance or requests removal of NIV secondary to self-reported discomfort, anxiety, or claustrophobia
   3. Other reason that the physician judges the patient to be intolerant of NIV or agitated, not captured above, or feels that the patient would benefit from titrated sedation for other reasons.

Exclusion Criteria:

1. Absence of a functioning pacemaker with one of the following: a-Persistent bradycardia defined as a heart rate (HR) ≤60bpm; b-Second or third-degree heart block; or c- Tachybrady syndrome
2. Persistent hypotension, defined as a mean arterial pressure (MAP) ≤65mmHg despite volume resuscitation and vasopressors
3. Imminent need for endotracheal intubation as determined by healthcare team
4. Patient's goals of care do not include intubation and IMV
5. Patient is not for vasopressors or inotropic support
6. Death is deemed imminent and inevitable
7. Patient is currently on a dexmedetomidine infusion for a duration of \> 12 hours
8. Previously enrolled in the inDEX trial
9. Acute liver failure with hepatic encephalopathy INR \> 3 and/or bilirubin \> 300
10. Current pregnancy or breast feeding
11. Known allergy to dexmedetomidine
12. Patients receiving Amphotericin B or Diazepam
13. Treating physician does not believe that participation in the trial is in the best interest of the patient (reasons for refusal will be captured)

Where this trial is running

Surrey, British Columbia and 5 other locations

• Fraser Health Authority — Surrey, British Columbia, Canada (NOT_YET_RECRUITING)
• Brockville General Hospital — Brockville, Ontario, Canada (NOT_YET_RECRUITING)
• St. Joseph's Healthcare Hamilton — Hamilton, Ontario, Canada (RECRUITING)
• Juravinski Hospital and Cancer Centre — Hamilton, Ontario, Canada (NOT_YET_RECRUITING)
• North York General Hospital — Toronto, Ontario, Canada (NOT_YET_RECRUITING)
• Sinai Health System — Toronto, Ontario, Canada (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Kimberley Lewis, MD — St. Joseph's Healthcare Hamilton
• Study coordinator: Kimberley Lewis, MD

Conditions: Non-Invasive Ventilation