Non-invasive Ventilation and Dex in Critically Ill Adults

NCT ID: NCT04878510

Last Updated: 2024-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-07
• Study Completion Date: 2024-04-21

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.

Detailed Description

1. BACKGROUND:

Non-invasive ventilation (NIV) is a life-saving intervention for patients with acute respiratory failure (ARF). Patients may find NIV intolerable and ultimately fail NIV requiring intubation and invasive mechanical ventilation (IMV). 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. Current guidelines lack recommendations on which sedative, if any at all, should be used during NIV due to the paucity of reliable data. Dexmedetomidine (dex) is a relatively new sedative. It 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. Dex has been recommended to use over benzodiazepines for sedation during IMV in critically ill adults, particularly if delirium is precluding weaning.

2. HYPOTHESIS:

We hypothesize that dexmedetomidine, when compared to placebo, reduces NIV failure in hospitalized adults with acute respiratory failure and agitation or NIV intolerance.

3. OBJECTIVES:

To evaluate the feasibility of assessing if dexmedetomidine compared to placebo results in a reduction of non-invasive ventilation failure in patients admitted to the hospital with acute respiratory failure. This will subsequently inform a large, pragmatic, powered trial to definitively address the question.

4. METHODS

4.1 Study design: The inDEX trial is a pragmatic, international, multi-centered, stratified, randomized, parallel-group, double-blind, placebo-controlled vanguard trial. Patients, investigators, healthcare team, data collectors, outcome assessors, and the statistician will be blinded to trial arms.

4.2 Allocation and randomization: Local Research Coordinators (RC) will randomize eligible patients in a fixed 1:1 allocation using undisclosed variable block sizes of four, six, or eight. The randomization will be achieved using a random number sequence prepared by an independent statistician. The independent statistician will have access to the random number sequence and it will be provided to the research pharmacist. Upon request by the local research coordinator, the research pharmacist will provide the care team with either placebo or dexmedetomidine, according to the randomization schedule. 4.3 Blinding: Both dexmedetomidine and normal saline placebo will be given as continuous infusion. To minimize performance and ascertainment biases, and maintain blinding of patients, investigators, clinical staff, and RCs; a Research Pharmacist, who is not involved in assessment of patient outcomes or patient care, will prepare infusion bags. Titration of the infusion rate for both arms will follow an identical volume-based titration algorithm. Despite optimal blinding efforts, it is possible that the care team may be able to determine who is receiving dexmedetomidine based on improvement in NIV tolerance and/or the decrease in heart rate and blood pressure. However, the cointerventions may also improve tolerance, and can certainly cause a reduction in heart rate and blood pressure.

Conditions

Respiratory Insufficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dexmedetomidine Intervention

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).

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: 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.

Control Intervention

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Normal saline placebo will be given as continuous infusion.

Interventions

Dexmedetomidine

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.

Intervention Type: DRUG

Placebo

Normal saline placebo will be given as continuous infusion.

Intervention Type: OTHER

Other Intervention Names

Precedex

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

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)

2. Patient expresses intolerance or requests removal of NIV secondary to self-reported discomfort, anxiety, or claustrophobia

3. Other reason that the physician feels the patient is intolerant of NIV or agitated, not captured above (all reasons will be recorded)

Exclusion Criteria

1. 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

2. Persistent hypotension, defined as a mean arterial pressure (MAP) ≤60mmHg despite volume resuscitation and vasopressors

3. Acute hepatic failure

4. Known allergy to dexmedetomidine

5. Pregnancy

6. Acute withdrawal from drugs or alcohol

7. Patients with post-extubation respiratory failure

8. Imminent need for endotracheal intubation

9. Death is deemed imminent and inevitable

10. Patient's goals of care do not include intubation and IMV

11. Patients already on dexmedetomidine at time of enrollment

12. Previously enrolled in the inDEX trial

13. Treating physician refuses enrollment (reasons for refusal will be captured)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Joseph's Healthcare Hamilton

OTHER

Sponsor Role: lead

Responsible Party

Kimberley Lewis

Clinical Scholar; Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kimberley Lewis, MD

Role: PRINCIPAL_INVESTIGATOR

Research Institute of St Joseph's Healthcare Hamilton

Locations

Monash Medical Centre - Monash Health

Melbourne, , Australia

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

King Abdulaziz Medical City - Riyadh

Riyadh, , Saudi Arabia

Countries

Australia; Canada; Saudi Arabia

Other Identifiers

13205

Identifier Type: -

Identifier Source: org_study_id