Non-invasive Ventilation and Dex in Critically Ill Adults

NCT04878510 | Completed Phase 3

• 1 other identifier: 13205
• Study Type: interventional
• Target: 24
• Locations: 3 countries
• Sites: 3

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 Vanguard 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. The results from this pilot trial, will subsequently inform a large, pragmatic, powered trial to definitively address the question.

Conditions

Respiratory Insufficiency

Keywords

Non-Invasive Ventilation; Sedation; Randomized Control Trial; Acute Respiratory Failure

Outcome Measures

Primary Outcomes (3)

• Recruitment Rate

  The rate in which patients are enrolled, by calculating the mean number of recruited patients compared to the number of patients screened.

  At the completion of the trial (approximately 1 year).

• Protocol Adherence; Proportion of patients assigned to the experimental arm that received the intervention and those assigned to the control arm that did not receive the intervention.

  Adherence will be calculated as the proportion of patients assigned to the experimental arm that received the intervention and those assigned to the control arm that did not receive the intervention.

  At the completion of the trial (approximately 1 year).

• Consent Rate

  The consent rate will be calculated as the overall proportion of substitute decision makers or patients who consented to be enrolled out of those approached.

  At the completion of the trial (approximately 1 year).

Secondary Outcomes (20)

• Acute care unit outcomes; Non-invasive ventilation (NIV) failure

  28 days post-randomization.

• Acute care unit outcomes; Acute Care Unite Length of Stay

  60 days post-randomization.

• Acute care unit outcomes; Duration of invasive mechanical ventilation

  60 days post-randomization.

• Acute care unit outcomes; Ventilation free Days

  28 days post-randomization.

• Process Outcomes; Number of patient-initiated device removal episodes.

  4 days post-randomization.

Study Arms (2)

Dexmedetomidine Intervention

EXPERIMENTAL

Patients randomized to the experimental arm will receive dexmedetomidine. At initiation, a bolus will NOT be administered. In keeping with Health Canada. Guidelines, the infusion will start at a mid-range dose of 0.6mcg/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 (Richmond Agitation-Sedation Scale \[RASS\] = -2 to +1 or Riker Sedation-Agitation Scale \[SAS\] 3-4).

Drug: Dexmedetomidine

Control Intervention

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 50mL of 0.9% sodium chloride and labeled as per Health Canada guidance for labelling pharmaceutical drugs for use in humans.

Other: Placebo

Interventions

Dexmedetomidine DRUG

Dexmedetomidine is an α2-adrenergic agonist sedative commonly used in invasive mechanical ventilation that promotes patient wakefulness, has no effect on respiratory drive, has important analgesic properties, and when compared to γ-aminobutyric acid receptor agonists like benzodiazepines, reduces delirium.

Also known as: Precedex

Dexmedetomidine Intervention

Placebo OTHER

Normal saline placebo will be given as continuous infusion.

Control Intervention

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
• 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)
• Patient expresses intolerance or requests removal of NIV secondary to self-reported discomfort, anxiety, or claustrophobia
• Other reason that the physician feels the patient is intolerant of NIV or agitated, not captured above (all reasons will be recorded)

You may not qualify if:

• Absence of a functioning pacemaker with one of the following: a-Persistent bradycardia defined as a heart rate (HR) ≤50bpm; b-Second or third-degree heart block; or c- Tachybrady syndrome
• Persistent hypotension, defined as a mean arterial pressure (MAP) ≤60mmHg despite volume resuscitation and vasopressors
• Acute hepatic failure
• Known allergy to dexmedetomidine
• Pregnancy
• Acute withdrawal from drugs or alcohol
• Patients with post-extubation respiratory failure
• Imminent need for endotracheal intubation
• Death is deemed imminent and inevitable
• Patient's goals of care do not include intubation and IMV
• Patients already on dexmedetomidine at time of enrollment
• Previously enrolled in the inDEX trial
• Treating physician refuses enrollment (reasons for refusal will be captured)

Sponsors & Collaborators

• St. Joseph's Healthcare Hamilton: lead

Study Sites (3)

Monash Medical Centre - Monash Health

Melbourne, Australia

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N4A6, Canada

Location

King Abdulaziz Medical City - Riyadh

Riyadh, Saudi Arabia

Location

MeSH Terms

Conditions

Respiratory Insufficiency

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Kimberley Lewis, MD

  Research Institute of St Joseph's Healthcare Hamilton

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: To minimize performance and ascertainment biases, and maintain blinding of patients, investigators, clinical staff, and research coordinators; a Research Pharmacist, who is not involved in assessment of patient outcomes or patient care, will prepare infusion bags
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Scholar; Principal Investigator

Model Details: The inDEX trial is a pragmatic, international, multi-centered, stratified, randomized, parallel-group, double-blind, placebo-controlled vanguard trial.

Study Record Dates

• First Submitted: April 25, 2021
• First Posted: May 7, 2021
• Study Start: March 7, 2022
• Primary Completion: April 21, 2024
• Study Completion: April 21, 2024
• Last Updated: October 28, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); SA (1); AU (1)