Respiratory InsufficiencyPhase 4SPICEIVNCT06251375
Early Sedation With Dexmedetomidine vs. Placebo in Older Ventilated Critically Ill Patients
A Phase 4 study testing Dexmedetomidine in people with Respiratory Insufficiency, run by St. Joseph's Healthcare Hamilton at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Respiratory Insufficiency
- What is being tested?
- Dexmedetomidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 1 siteCanada
- Study dates
- 7 Sep 2025to 31 Jan 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Irene Armanious contact
Canada1 site
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
Sumesh Shah, CCRP, 416-586-4800 ext. 1164, sumesh.shah@sinaihealth.ca
Samgeeta Mehta, MD
About this study
Official title: Sedation Practice in Intensive Care Evaluation (SPICE IV) Early Sedation With Dexmedetomidine vs. Placebo in Older Ventilated Critically Ill Patients: A Prospective, Multi-Centre, Double-Blind, Randomized, Controlled Trial
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.
Read the detailed description
- BACKGROUND Current guidelines highlight evidence gaps to be addressed in future sedation trials, particularly the need for adequately powered trials to evaluate impact of sedative choice in older adults, as they have a highest overall mortality and the most common demographic to require an ICU admission of all age groups. Dexmedetomidine, an α2-adrenergic agonist sedative, may be the solution. The SPICE III trial, a prelude to the SPICE IV study, evaluated early sedation with dexmedetomidine versus usual care sedation in 4000 critically ill patients. The SPICE III trial identified a heterogeneity of treatment effect (HTE) on the primary outcome of 90-day mortality, suggesting lower mortality in older patients. To further evaluate the observed HTE, SPICE IV was designed as a randomized double-blind placebo-controlled trial with a study population restricted to patients at or older than 65 years of age.
- HYPOTHESIS Early sedation with DEX as the primary sedative agent reduces 90-day all-cause mortality in invasively mechanically ventilated patients who are ≥ 65 years of age.
- OBJECTIVES The primary aim is to determine whether, in invasively mechanically ventilated patients who are ≥ 65 years of age, early sedation with DEX as the primary sedative agent reduces 90-day all-cause mortality. The secondary aims are to assess the effect of DEX on ventilator free days, coma and delirium free days, major adverse kidney events (MAKE-28) at day 28, duration of ventilation, and hospital stay in survivors.
- METHODS
This 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. Randomization will occur via a secured website. A total of 300 patients will be recruited across Canadian centres and assigned in a 1:1 ratio to either: early dexmedetomidine (Intervention arm) or placebo (Control arm).Patients in the active intervention arm will receive a dexmedetomidine infusion starting at a recommended dose of 1 µg/kg/h without a loading dose. Patients in the control arm will receive normal saline at equivalent doses. Analgesia will be optimized in both groups as clinically indicated. The sedation target is defined by the Richmond Agitation-Sedation Scale (RASS) score of -1 to +1 at all times, unless otherwise clinically indicated.
- Conditions
- Respiratory Insufficiency
- Being tested
- Dexmedetomidine, Placebo
- Keywords
- Mechanical Ventilation, Sedation, Randomized Control Trial, Acute Respiratory Failure
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
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.
PlaceboOther
Normal saline placebo will be given as continuous infusion.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
90-day all-cause mortality
Measured: 90 days
Secondary outcomes (5)
Number of days alive and free of coma and delirium
Measured: 28 days
Number of days alive and ventilator free
Measured: 28 days
Major Adverse Kidney Events
Mortality + Acute Kidney Injury > stage II, defined by Kidney Disease Improving Global Outcome (KDIGO) definition
Measured: 28 days
Duration of mechanical ventilation in survivors
Measured: 28 days
Hospital Length of Stay in survivors
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2024
- Study start7 Sep 2025 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Respiratory InsufficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St. Joseph's Healthcare Hamilton
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kimberley Lewis, St. Joseph's Healthcare Hamilton
- Investigators
- Kimberley Lewis, MD, Principal investigator, St. Joseph's Healthcare Hamilton/McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06251375
- Sponsor's protocol ID
- 4569
- Acronym
- SPICEIV
- Status last verified
- Sep 2025
- First submitted
- 1 Feb 2024
- Last updated
- 10 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sedation Practice in Intensive Care Evaluation (SPICE IV) Early Sedation With Dexmedetomidine vs. Placebo in Older Ventilated Critically Ill Patients: A Prospective, Multi-Centre, Double-Blind, Randomized, Controlled Trial
- ClinicalTrials.gov ID
- NCT06251375
- Acronym / sponsor ID
- SPICEIV / 4569
- Conditions
- Respiratory Insufficiency
- Keywords
- Mechanical Ventilation, Sedation, Randomized Control Trial, Acute Respiratory Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- St. Joseph's Healthcare HamiltonUniversity, hospital or other
- Study start
- 7 Sep 2025 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Jan 2028 (estimated)
- First posted
- 9 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- BACKGROUND Current guidelines highlight evidence gaps to be addressed in future sedation trials, particularly the need for adequately powered trials to evaluate impact of sedative choice in older adults, as they have a highest overall mortality and the most common demographic to require an ICU admission of all age groups. Dexmedetomidine, an α2-adrenergic agonist sedative, may be the solution. The SPICE III trial, a prelude to the SPICE IV study, evaluated early sedation with dexmedetomidine versus usual care sedation in 4000 critically ill patients. The SPICE III trial identified a heterogeneity of treatment effect (HTE) on the primary outcome of 90-day mortality, suggesting lower mortality in older patients. To further evaluate the observed HTE, SPICE IV was designed as a randomized double-blind placebo-controlled trial with a study population restricted to patients at or older than 65 years of age.
- HYPOTHESIS Early sedation with DEX as the primary sedative agent reduces 90-day all-cause mortality in invasively mechanically ventilated patients who are ≥ 65 years of age.
- OBJECTIVES The primary aim is to determine whether, in invasively mechanically ventilated patients who are ≥ 65 years of age, early sedation with DEX as the primary sedative agent reduces 90-day all-cause mortality. The secondary aims are to assess the effect of DEX on ventilator free days, coma and delirium free days, major adverse kidney events (MAKE-28) at day 28, duration of ventilation, and hospital stay in survivors.
- METHODS
This 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. Randomization will occur via a secured website. A total of 300 patients will be recruited across Canadian centres and assigned in a 1:1 ratio to either: early dexmedetomidine (Intervention arm) or placebo (Control arm).Patients in the active intervention arm will receive a dexmedetomidine infusion starting at a recommended dose of 1 µg/kg/h without a loading dose. Patients in the control arm will receive normal saline at equivalent doses. Analgesia will be optimized in both groups as clinically indicated. The sedation target is defined by the Richmond Agitation-Sedation Scale (RASS) score of -1 to +1 at all times, unless otherwise clinically indicated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine Intervention | Experimental | Drug: DexmedetomidinePatients 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. |
| Control Intervention | Placebo comparator | Other: PlaceboThose 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. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexmedetomidineDexmedetomidine 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. | Drug | Dexmedetomidine Intervention |
| PlaceboNormal saline placebo will be given as continuous infusion. | Other | Control Intervention |
Primary outcome
Mortality
Time frame: 90 days
90-day all-cause mortality
5 secondary outcomes
Number of days alive and free of coma and delirium
Time frame: 28 days
Number of days alive and ventilator free
Time frame: 28 days
Major Adverse Kidney Events
Time frame: 28 days
Duration of mechanical ventilation in survivors
Time frame: 28 days
Hospital Length of Stay in survivors
Time frame: 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Irene Armanious contact
Kimberley Lewis, MD principal investigator
St. Joseph's Healthcare Hamilton/McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexmedetomidine in people with Respiratory Insufficiency, run by St. Joseph's Healthcare Hamilton at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jose Estrada (905-522-1155 ext. 32873, jestrada@stjosham.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2025.