Early Sedation With Dexmedetomidine vs. Placebo in Older Ventilated Critically Ill Patients

NCT06251375 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 4569
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Sedation remains a ubiquitous and crucial component of intensive care treatments in critically ill mechanically ventilated patients. Sedation relieves anxiety, reduces distress, and promotes tolerance of endotracheal intubation and associated life-sustaining interventions such as mechanical ventilation, cardiovascular assistance, and renal support. Thus, choosing the optimal sedative agent is vital to patient comfort, safety, and survival. Despite more than 20 years of intensive care sedation research, there is still no consensus on what constitutes best sedation practice. The Society of Critical Care Medicine, the premier critical care organisation in North America, published the 2018 Clinical Practice Guidelines on the management of Pain, Agitation/Sedation, Delirium, Immobility and Sleep (PADIS) disruption (chaired by our primary applicant W.A.) and issued weak recommendations to provide analgesia before sedation, to target light sedation whenever clinically feasible, and to use either dexmedetomidine or propofol over midazolam for the sedation of mechanically ventilated critically ill patients. Similarly, the American Thoracic Society produced a set of Clinical Practice Guidelines to promote liberation and weaning from mechanical ventilation in critically ill patients, with weak recommendations for the use of non-benzodiazepines as primary sedatives and to target light sedation when clinically possible. A weak recommendation was issued in an Intensive Care Medicine Rapid Practice Guideline published in 2022 to use dexmedetomidine over propofol for sedation of critically ill adults, if the desired outcome is a reduction in delirium. These guidelines, however, do not consider age-dependent pharmacokinetics and pharmacodynamics, illness severity, timing of sedative administration, operative vs medical reason for admission, or the changing dynamics of sedation practice at different phases of critical illness. The lack of high-level evidence to inform sedation practice in the critically ill has led to approaches that are mainly opinion-based and lack the support of evidence from large multicentre, international randomised clinical trials.

Conditions

Respiratory Insufficiency

Keywords

Mechanical Ventilation; Sedation; Randomized Control Trial; Acute Respiratory Failure

Outcome Measures

Primary Outcomes (1)

• Mortality

  90-day all-cause mortality

  90 days

Secondary Outcomes (5)

• Number of days alive and free of coma and delirium

  28 days

• Number of days alive and ventilator free

  28 days

• Major Adverse Kidney Events

  28 days

• Duration of mechanical ventilation in survivors

  28 days

• Hospital Length of Stay in survivors

  28 days

Study Arms (2)

Dexmedetomidine Intervention

EXPERIMENTAL

Patients randomized to the experimental arm will receive dexmedetomidine. The study medication will be reconstituted by mixing 4 vials (8 ml) into a 100 ml bag of normal saline or 5% dextrose, this is the preferred dilution, or 2 vials (4ml) into 50 ml syringe to an equivalent concentration of 8 mcg/ml of dexmedetomidine. The constituted infusion is stable at room temperature for up to 24 hours. The recommended starting infusion rate is equivalent to 1 µg/kg/h of dexmedetomidine, without loading or bolus. This will be titrated to an equivalent dexmedetomidine dose of 0 to 1.0 µg/kg/h according to study algorithm to maintain target sedation of Richmond Agitation-Sedation Scale (RASS) score of -1 to +1.

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. The placebo is a matching vial containing 2 mL sterile normal saline.

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.

Dexmedetomidine Intervention

Placebo OTHER

Normal saline placebo will be given as continuous infusion.

Control Intervention

Eligibility Criteria

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

You may qualify if:

• Age ≥ 65 years
• Intubated and receiving invasive mechanical ventilation in an intensive care unit
• The treating clinicians believe that the patient will remain intubated and ventilated until the day after tomorrow (i.e. unlikely to be extubated the following day)
• The patient requires immediate ongoing sedative medication for comfort, safety and to facilitate the delivery of life support measures.

You may not qualify if:

• Has been intubated (excluding time spent intubated within an operating theatre or transport) for greater than 12 hours, with an additional 6-hour grace period, a total of 18 hours, in an intensive care unit
• Proven or suspected acute primary brain lesion such as traumatic brain injury, haemorrhage, stroke, or hypoxic brain injury
• Proven or suspected spinal cord injury or other pathology that may result in permanent or prolonged weakness
• Admission as a consequence of a suspected or proven drug overdose or burns
• Administration of or need for ongoing neuromuscular blockade
• A mean arterial blood (MAP) pressure that is less than 50 mmHg, despite adequate resuscitation and vasopressor support at time of randomization
• Heart rate less than 55 beats per minute or a high grade atrio-ventricular block in the absence of a functioning pacemaker
• Known sensitivity to dexmedetomidine
• Acute fulminant hepatic failure with EITHER
• hepatic encephalopathy OR
• bilirubin (\>300 µmol/l) and INR (\>3.5), or both, without prior hepatic dysfunction.
• Receiving full time residential nursing care
• Death is deemed both imminent and inevitable and either the attending physician, patient or substitute decision maker is not committed to active treatment
• Underlying disease that makes survival to 90 days unlikely
• Previously enrolled in the SPICE IV study

Sponsors & Collaborators

• St. Joseph's Healthcare Hamilton: lead

Study Sites (1)

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

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

  St. Joseph's Healthcare Hamilton/McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jose Estrada

CONTACT

905-522-1155; jestrada@stjosham.on.ca

Irene Armanious

CONTACT

iarmanio@stjosham.on.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: To maintain blinding of patients, investigators, clinical staff, and research coordinators, pre-packaged study medication kits will be used. Upon randomization, the website will assign a unique study number and a unique 'medication kit number' to each participant. The unique medication kit number is matched to blinded study drug according to the patient's treatment allocation, supplied to the site. Each medication kit will contain either: dexmedetomidine 200 µg/2 ml vials or normal saline vials. Blinding of study medications within the medication kit will be achieved by identical labelled 2 ml vials.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The SPICE IV trial is a prospective, double-blind, placebo controlled, randomised trial of early sedation with dexmedetomidine in invasively mechanically ventilated patients who are ≥ 65 years of age and who are expected to remain ventilated more than one calendar day after randomization

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 9, 2024
• Study Start: September 7, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: September 10, 2025

Record last verified: 2025-09

Locations

CA (1)