Non-invasive Ventilation and Dexmedetomidine in Critically Ill Adults

NCT06259565 | Recruiting Phase 3 DMC

• 1 other identifier: 4257
• Study Type: interventional
• Target: 846
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Non-Invasive Ventilation

Outcome Measures

Primary Outcomes (1)

• NIV Failure

  The primary outcome is NIV failure, defined by either mortality or intubation

  28 days

Secondary Outcomes (5)

• Physiologic outcomes: Incidence of delirium

  28 days

• Physiologic outcomes: Incidence of agitation

  28 days

• Major morbidity or mortality outcomes: Intubation

  14 days

• Major morbidity or mortality outcomes: ICU Mortality

  28 days

• Major morbidity or mortality outcomes: Hospital Mortality

  90 days

Other Outcomes (4)

• Functional Outcome: EQ-5D-5L

  90 days

• Functional Outcome: EQ-VAS

  90 days

• Functional Outcome: Clinical Frailty Scale

  90 days

Study Arms (2)

Dexmedetomidine Intervention

EXPERIMENTAL

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. Patients randomized to the experimental arm will receive dexmedetomidine. At initiation, a bolus will NOT be administered. In keeping with Health Canada Guidelines, we will start the infusion at a mid-range dose of 0.5mcg/kg/h with titration either up or down by 0.1mcg/kg/h every 20-30 minutes to a maximum rate of 1.2mcg/kg/h to maintain light sedation (RASS = -2 to +1 or SAS 3-4). Each bag will be composed of composed of dexmedetomidine 4mcg/mL(in 0.9% sodium chloride) prepared as a volume of 100mL and labeled as per Health Canada guidance for labelling pharmaceutical drugs for use in humans.

Drug: Dexmedetomidine

Placebo Control

PLACEBO COMPARATOR

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

Other: Placebo Control

Interventions

Dexmedetomidine DRUG

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

Dexmedetomidine Intervention

Placebo Control OTHER

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

Placebo Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Patient receiving any NIV modality for acute respiratory failure of any etiology
• 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
• Presence of one or more of the following after optimized NIV treatment:
• 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)
• Patient expresses intolerance or requests removal of NIV secondary to self-reported discomfort, anxiety, or claustrophobia
• 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.

You may not qualify if:

• 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
• Persistent hypotension, defined as a mean arterial pressure (MAP) ≤65mmHg despite volume resuscitation and vasopressors
• Imminent need for endotracheal intubation as determined by healthcare team
• Patient's goals of care do not include intubation and IMV
• Patient is not for vasopressors or inotropic support
• Death is deemed imminent and inevitable
• Patient is currently on a dexmedetomidine infusion for a duration of \> 12 hours
• Previously enrolled in the inDEX trial
• Acute liver failure with hepatic encephalopathy INR \> 3 and/or bilirubin \> 300
• Current pregnancy or breast feeding
• Known allergy to dexmedetomidine
• Patients receiving Amphotericin B or Diazepam
• Treating physician does not believe that participation in the trial is in the best interest of the patient (reasons for refusal will be captured)

Sponsors & Collaborators

• St. Joseph's Healthcare Hamilton: lead
• Population Health Research Institute: collaborator

Study Sites (6)

Fraser Health Authority

Surrey, British Columbia, V3T 0H1, Canada

NOT YET RECRUITING

Brockville General Hospital

Brockville, Ontario, K6V 1S8, Canada

NOT YET RECRUITING

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

RECRUITING

Juravinski Hospital and Cancer Centre

Hamilton, Ontario, L8V 1C3, Canada

NOT YET RECRUITING

North York General Hospital

Toronto, Ontario, M2K 1E1, Canada

NOT YET RECRUITING

Sinai Health System

Toronto, Ontario, M5G 1X5, Canada

NOT YET RECRUITING

MeSH Terms

Interventions

Dexmedetomidine

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kimberley Lewis, MD

  St. Joseph's Healthcare Hamilton

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kimberley Lewis, MD

CONTACT

(289)775-7334; kimberley.lewis@medportal.ca

Jose Estrada

CONTACT

jestrada@stjosham.on.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Patients randomized to the experimental arm will receive dexmedetomidine. We will start the infusion at a mid-range dose of 0.5mcg/kg/h with titration either up or down by 0.1mcg/kg/h every 20-30 minutes to a maximum rate of 1.2mcg/kg/h to maintain light sedation (RASS = -2 to +1 or SAS = 3 to 4). The study drug will always be titrated to the lowest possible dose with preserved effect. Each bag will be composed of two 100 mcg/mL dexmedetomidine vials (2ml vials) mixed in a 96mL 0.9% sodium chloride mini-bag (4mcg/ml) and labeled as per Health Canada guidance for labelling pharmaceutical drugs for use in humans. The trial protocol does not allow an initial bolus of dexmedetomidine for safety reasons.

Study Record Dates

• First Submitted: December 27, 2023
• First Posted: February 14, 2024
• Study Start: July 29, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): January 31, 2030
• Last Updated: September 10, 2025

Record last verified: 2025-09

Locations

CA (6)