Brain Ischemia, Hemorrhage, Intracranial, Stroke, Vasospasm, Intracranial
Conditions
Keywords
Dexmedetomidine, Endovascular procedure, Stroke, Vasospasm, intracranial, Conscious sedation
Brief summary
Dexmedetomidine is a unique sedative medication able to provide sedation without causing respiratory depression and maintaining neurological functions. Patients having an acute ischemic stroke and need to undergo endovascular therapy require constant assessment of their neurological status prior, during and after the interventional procedure. In this study the investigators will compare the efficacy of Dexmedetomidine to other standard sedative medications in providing optimal sedative effect while maintaining neurological function.
Detailed description
Precedex is a unique FDA-approved intravenous medication for conscious sedation in that it allows for arousable sedation, which is particularly appealing for use in patients with compromised neurologic function. While Precedex has been shown to be equivalent, if not superior to, conventional sedation in the procedural setting, it has not yet been evaluated in the setting of endovascular treatment of acute stroke. This setting is particularly ripe for evaluation, as there is currently controversy over the best method for management of patient sedation in light of the auxiliary need to preserve neurologic function. In order to evaluate the benefit of Precedex in this setting, it must be compared to the usual standard of care. Through the investigators double blinded randomized trial, the investigators will obtain information on the comparison between two arms, one receiving Precedex and the other the usual standard of care at the investigators institution, for achieving and maintaining a pre-defined level of conscious sedation, while preserving baseline neurologic status. This assessment will optimistically serve as the basis for future large-scale studies and ultimately to the establishment of Precedex as a first-line sedative in the management of acute stroke and cerebral vasospasm patients undergoing endovascular intervention.
Interventions
DRUGDexmedetomidine
Precedex will be given to randomized subjects in thi study to evaluate its efficacy in maintaining optimal sedation and preserving neurological exam.
DRUGFentanyl
Patients in the control arm will receive no medication or standard sedative drug for the interventional procedure.
DRUGMidazolam
Patients in the control arm will receive no medication or standard sedative drug for the interventional procedure.
Sponsors
Hospira, now a wholly owned subsidiary of Pfizer
University Hospitals Cleveland Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Patients with acute ischemic stroke who require endovascular intervention with whom mNIHSS score can be obtained * Patients with cerebral vasospasm suspiciousness with or without subarachnoid hemorrhage with whom mNIHSS score can be obtained.
Exclusion criteria
* History of severe hepatic disease or severe renal disease (GFR\<20). * Hemodynamic instability. * Pregnancy. * Known allergy to study drug. * Evidence or history of cardiac electrophysiology instability including uncontrolled hemodynamically unstable complex atrial/ventricular arrhythmia or conduction block at the time of evaluation with the exception of atrial fibrillation, and heart rate less than 60 or systolic blood pressure less than 90. * Respiratory compromise requiring intubation. * Any medical (including history of cardiac conduction block, major hepatic or renal disease) or laboratory abnormality that may increase the risk associated with the trial participation or drug administration or may interfere with interpretation of trial results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Numbers of Patient Movements (Events) That Delay or Adversely Affect the Procedure Performance and Safety. | Primary outcome will be assessed during the procedure, up to 4 hours. | Patient will be continuously monitored for movements that delays or adversely affect the performance of the procedure by the patient assessor in a safe and timely manner (an event). One minute interval between patient event assessments will be given to prevent subjective bias. After every one minute, it will be determined if an event has occurred. Over the length of the procedure, the total number of one-minute intervals with an event occurrence will be summed and then divided by the total of minutes in the procedure to obtain a standardized value as the primary outcome. This will allow for direct comparison of values across the procedures of varying length. This approach will be more systematic and more easily replicable than counting events directly, which requires interpretation as to when a movement event begins and ends, which can be difficult and more subjective. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Preserved Neurological Examination. | Up to 8 hours | Neurological status using modified NIHSS (National Institutes of Health Stroke Scale) is a 15-item neurologic examination stroke scale, between 0 and 4, with 0 being normal functioning and 4 being completely impaired. |
| Maintenance of Optimal Sedation Target in Both Groups. | Up to 8 hours | Both arms will be assessed by the patient assessor with RASS score measurement at baseline and every 20 minutes thereafter for the length of the procedure (up to 8 hours) and then averaged together to get one over all score . In the Dexmedetomidine arm the drug will be titrated by 0.1mcg/Kg/hour by the treating physician clinical judgment, in order to achieve and maintain RASS of 0 - 1. In the control arm the drug adjustment will not be based on the RASS score, but by physician discretion only. It is a 10-point scale to determine sedation, with a score from +4 (very combative, violent, dangerous to staff) to -5 (unarousable, no response to voice or physical stimulation). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dexmedetomidine Arm Precedex will be started after randomization/prior to catheterization and will be stopped at the end of the procedure. It will be used for an average of 90 minutes and will be used as a continuous intravenous infusion started at 0.3 mcg/kg/hour. If HR \> 80 and BP \> 120/70, a full loading dose (1.0 mcg/kg/hour) will be administered over 10 minutes. If HR is 60 - 80 or systolic BP is 90 - 120, or age \> 65 years, a reduced loading dose of 0.5 mcg/kg will be given over 10 minutes. If no volume overload history, 500mL of colloid (hespan or albumin) will be bolused with 0.2mg of glycopyrrolate. Every 10 minutes, Precedex will be titrated by 0.1 mcg/kg/hour to achieve and maintain RASS of 0 to -1.
Dexmedetomidine: Precedex will be given to randomized subjects in thi study to evaluate its efficacy in maintaining optimal sedation and preserving neurological exam. | 4 |
| Control Arm Our usual standard of care is to attempt the intervention without sedation. As per attending physician discretion, Fentanyl (50mcg) and/or Midazolam (0.5 mg) intravenous boluses will be used to control aggressive patient movement that adversely affects the technical capacity of the procedure. The boluses will be repeated at interval of 10 minutes, as necessary. Control arm patients will receive a normal saline placebo drip for the purposes of ensuring patient assessor blindness.
Fentanyl: Patients in the control arm will receive no medication or standard sedative drug for the interventional procedure.
Midazolam: Patients in the control arm will receive no medication or standard sedative drug for the interventional procedure. | 3 |
| Total | 7 |
Baseline characteristics
| Characteristic | Total | Dexmedetomidine Arm | Control Arm |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 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 | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 0 / 4 | 0 / 3 |
| serious Total, serious adverse events | 0 / 4 | 0 / 3 |
Outcome results
Primary
Numbers of Patient Movements (Events) That Delay or Adversely Affect the Procedure Performance and Safety.
Patient will be continuously monitored for movements that delays or adversely affect the performance of the procedure by the patient assessor in a safe and timely manner (an event). One minute interval between patient event assessments will be given to prevent subjective bias. After every one minute, it will be determined if an event has occurred. Over the length of the procedure, the total number of one-minute intervals with an event occurrence will be summed and then divided by the total of minutes in the procedure to obtain a standardized value as the primary outcome. This will allow for direct comparison of values across the procedures of varying length. This approach will be more systematic and more easily replicable than counting events directly, which requires interpretation as to when a movement event begins and ends, which can be difficult and more subjective.
Time frame: Primary outcome will be assessed during the procedure, up to 4 hours.
Population: Data was not collected for one patient in the Dexmedetomidine arm.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine Arm | Numbers of Patient Movements (Events) That Delay or Adversely Affect the Procedure Performance and Safety. | 30 Events | Standard Deviation 27.07397 |
| Control Arm | Numbers of Patient Movements (Events) That Delay or Adversely Affect the Procedure Performance and Safety. | 36 Events | Standard Deviation 25.86503 |
Secondary
Maintenance of Optimal Sedation Target in Both Groups.
Both arms will be assessed by the patient assessor with RASS score measurement at baseline and every 20 minutes thereafter for the length of the procedure (up to 8 hours) and then averaged together to get one over all score . In the Dexmedetomidine arm the drug will be titrated by 0.1mcg/Kg/hour by the treating physician clinical judgment, in order to achieve and maintain RASS of 0 - 1. In the control arm the drug adjustment will not be based on the RASS score, but by physician discretion only. It is a 10-point scale to determine sedation, with a score from +4 (very combative, violent, dangerous to staff) to -5 (unarousable, no response to voice or physical stimulation).
Time frame: Up to 8 hours
Population: Data not collected for one patient on Dexmedetomidine arm.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine Arm | Maintenance of Optimal Sedation Target in Both Groups. | -1 score on a scale | Standard Deviation 2.417882 |
| Control Arm | Maintenance of Optimal Sedation Target in Both Groups. | 0 score on a scale | Standard Deviation 1.7754 |
Secondary
Preserved Neurological Examination.
Neurological status using modified NIHSS (National Institutes of Health Stroke Scale) is a 15-item neurologic examination stroke scale, between 0 and 4, with 0 being normal functioning and 4 being completely impaired.
Time frame: Up to 8 hours
Population: Data not collected for one patient in the dexmedetomidine arm
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Dexmedetomidine Arm | Preserved Neurological Examination. | 19 score on a scale | Standard Deviation 5.75 |
| Control Arm | Preserved Neurological Examination. | 18.5 score on a scale | Standard Deviation 2.250926 |