Critical Illness, Mechanical Ventilation
Conditions
Keywords
Hypnotics and Sedatives, Respiration, Artificial, Ventilators, Mechanical, Critical care, Intensive care, Physical therapy, Occupational therapy, Sedative medications
Brief summary
This is a randomized controlled trial to compare propofol to dexmedetomidine for prolonged sedation (\> 24 hours) in critically ill patients who require mechanical ventilation.
Detailed description
Mechanically ventilated critically ill patients are routinely given sedative and analgesic medications to relieve pain and anxiety associated with intubation, mechanical ventilation, and critical care in general. While integral in minimizing discomfort, these medications may increase mechanical ventilation time, the duration of intensive care unit (ICU) stay, ICU complications (e.g. delirium, ventilator associated pneumonia, venous thromboembolism), the morbidity associated with critical illness, and patient mortality. This study compares two sedative medications that have been used in patients who require a mechanical ventilator. Enrolled patients will be randomly assigned to receive propofol or dexmedetomidine for sedation while they require ventilatory support. All patients will also receive the pain medication fentanyl as needed.
Interventions
DRUGDexmedetomidine
continuous IV infusion 0.2 - 1.5 ucg/kg/hour titrated to target RASS
DRUGPropofol
continuous IV infusion (5 - 50 ucg/kg/min) titrated to target RASS
DRUGFentanyl
25 - 200 mcg IV every hour (as multiple IV pushes) as needed titrated to Non-Verbal Pain Scale
DRUGMidazolam
0.01 - 0.1 mg/kg IV push every 10 minutes as needed for agitation (RASS\>+2)
BEHAVIORALPhysical and Occupational Therapy
Daily therapy sessions targeting range of motion, strength, and mobility
Sponsors
Hospira, now a wholly owned subsidiary of Pfizer
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \>18 years old * mechanically ventilated through endotracheal tube * anticipated need for ventilation \> 48 hours * requiring sedative/analgesic medication
Exclusion criteria
* on mechanical ventilator \> 96 hours * primary neurologic disease * post cardiac arrest * do not speak English (assessment only English language validated) * pregnancy or lactation * active myocardial ischemia * second or third degree heart block * pancreatitis * elevated serum triglycerides (\> 400 mg/dL)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Days With Delirium | daily up to 28 days | delirium assessment using CAM-ICU |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Completing Mobility Milestones | Daily through day 28 | Milestones: sitting upright independently, standing independently, transfer to chair, marching in place, ambulating independently |
| Days on Ventilator | 60 days from enrollment | — |
| Days in ICU | 60 days from enollment | — |
| Mortality | 28 days from enrollment | — |
| Number of Participants With ICU Complications | daily through day 28 | — |
| Drug Efficacy According to Richmond Agitation Sedation Scale (RASS) Score | Daily up to day 28 | Richmond Agitation Sedation Scale (RASS). This is a validated scale that measures level of sedation. The scale ranges from -5 to +4. -5 refers to a state where one is unarousable, +4 refers to a state where one is combative. The median and inter-quartile range over all daily assessments will be provided. |
| Number of Patients Requiring Midazolam | during infusion of study medication through day 28 | — |
| Days in Hospital | 60 days from enrollment | — |
| Number of Patients Completing Activities of Daily Living | daily through day 28 | activities of daily living: eating, bathing, dressing, grooming, toileting |
| Number of Adverse Medication Effects | duration of infusion of study medication up to 28 days | — |
| Number of Patients Requiring Fentanyl | during infusion of study medication up to day 28 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dexmedetomidine Patients in this arm will receive continuous dexmedetomidine infusion (0.2 - 1.5 mcg/kg/hour) titrated to the target Richmond Agitation Sedation Scale for the duration of mechanical ventilation or 7 days on study, whichever is first.
Dexmedetomidine: continuous IV infusion 0.2 - 1.5 ucg/kg/hour titrated to target RASS
Fentanyl: 25 - 200 mcg IV every hour (as multiple IV pushes) as needed titrated to Non-Verbal Pain Scale
Midazolam: 0.01 - 0.1 mg/kg IV push every 10 minutes as needed for agitation (RASS\>+2)
Physical and Occupational Therapy: Daily therapy sessions targeting range of motion, strength, and mobility | 20 |
| Propofol Patients in this arm will receive propofol (5 - 50 mcg/kg/min) for sedation, titrated to the target Richmond Agitation Sedation Scale for the duration of mechanical ventilation or 7 days on study, whichever is first.
Propofol: continuous IV infusion (5 - 50 ucg/kg/min) titrated to target RASS
Fentanyl: 25 - 200 mcg IV every hour (as multiple IV pushes) as needed titrated to Non-Verbal Pain Scale
Midazolam: 0.01 - 0.1 mg/kg IV push every 10 minutes as needed for agitation (RASS\>+2)
Physical and Occupational Therapy: Daily therapy sessions targeting range of motion, strength, and mobility | 21 |
| Total | 41 |
Baseline characteristics
| Characteristic | Propofol | Total | Dexmedetomidine |
|---|---|---|---|
| Age, Continuous | 67 years | 63.8 years | 60.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 19 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Female | 9 Participants | 20 Participants | 11 Participants |
| Sex: Female, Male Male | 12 Participants | 21 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 21 |
| serious Total, serious adverse events | 0 / 20 | 0 / 21 |
Outcome results
Primary
Proportion of Days With Delirium
delirium assessment using CAM-ICU
Time frame: daily up to 28 days
Population: Study terminated early due to inability to maintain study drug supply in investigational pharmacy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine | Proportion of Days With Delirium | 0 proportion of days |
| Propofol | Proportion of Days With Delirium | .33 proportion of days |
Secondary
Days in Hospital
Time frame: 60 days from enrollment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine | Days in Hospital | 14.33 days |
| Propofol | Days in Hospital | 12.96 days |
Secondary
Days in ICU
Time frame: 60 days from enollment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine | Days in ICU | 6.39 days |
| Propofol | Days in ICU | 5.61 days |
Secondary
Days on Ventilator
Time frame: 60 days from enrollment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine | Days on Ventilator | 3.85 days |
| Propofol | Days on Ventilator | 4.05 days |
Secondary
Drug Efficacy According to Richmond Agitation Sedation Scale (RASS) Score
Richmond Agitation Sedation Scale (RASS). This is a validated scale that measures level of sedation. The scale ranges from -5 to +4. -5 refers to a state where one is unarousable, +4 refers to a state where one is combative. The median and inter-quartile range over all daily assessments will be provided.
Time frame: Daily up to day 28
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexmedetomidine | Drug Efficacy According to Richmond Agitation Sedation Scale (RASS) Score | -1 score on a scale |
| Propofol | Drug Efficacy According to Richmond Agitation Sedation Scale (RASS) Score | -1.6 score on a scale |
Secondary
Mortality
Time frame: 28 days from enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexmedetomidine | Mortality | 8 Participants |
| Propofol | Mortality | 12 Participants |
Secondary
Number of Adverse Medication Effects
Time frame: duration of infusion of study medication up to 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dexmedetomidine | Number of Adverse Medication Effects | 0 number of events |
| Propofol | Number of Adverse Medication Effects | 0 number of events |
Secondary
Number of Participants With ICU Complications
Time frame: daily through day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexmedetomidine | Number of Participants With ICU Complications | 0 Participants |
| Propofol | Number of Participants With ICU Complications | 0 Participants |
Secondary
Number of Patients Completing Activities of Daily Living
activities of daily living: eating, bathing, dressing, grooming, toileting
Time frame: daily through day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexmedetomidine | Number of Patients Completing Activities of Daily Living | 7 Participants |
| Propofol | Number of Patients Completing Activities of Daily Living | 6 Participants |
Secondary
Number of Patients Completing Mobility Milestones
Milestones: sitting upright independently, standing independently, transfer to chair, marching in place, ambulating independently
Time frame: Daily through day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexmedetomidine | Number of Patients Completing Mobility Milestones | 7 Participants |
| Propofol | Number of Patients Completing Mobility Milestones | 6 Participants |
Secondary
Number of Patients Requiring Fentanyl
Time frame: during infusion of study medication up to day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexmedetomidine | Number of Patients Requiring Fentanyl | 3 Participants |
| Propofol | Number of Patients Requiring Fentanyl | 6 Participants |
Secondary
Number of Patients Requiring Midazolam
Time frame: during infusion of study medication through day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dexmedetomidine | Number of Patients Requiring Midazolam | 3 Participants |
| Propofol | Number of Patients Requiring Midazolam | 0 Participants |