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All enrolled participants completed the study protocol but the study was terminated prior to the goal number of participants due to low recruitment
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This study aims to examine the use of protocol directed sedation using the Duke PAD protocol with the current sedation medications of propofol or dexmedetomidine compared to the PAD protocol with midazolam, per cardiac intensive care unit (CICU) usual care, as an initial step toward understanding the best management of sedation in these patients.
The optimal approach to management of sedation in the Intensive Care Unit (ICU) has become a topic of increasing interest. The most recent guidelines outline the pharmacologic mechanisms of commonly used medications as well as scales on which to measure goals of pain, sedation, agitation and delirium in the critically ill patient. This guideline is based on a cadre of randomized controlled trials examining the medications in the medical intensive care unit and post cardiac surgery patient. Notably, in each of the trials, patients presenting with acute myocardial infarction, heart failure or cardiogenic shock have been excluded or largely underrepresented.
Using the current guidelines as a foundation, a new pain, agitation and delirium (PAD) protocol, which prioritizes the use of propofol or dexmedetomidine for sedation, was developed and instituted at Duke University Hospital. However, use of this protocol in the CICU has raised important considerations. Some of these stem from the specific hemodynamic characteristics of the population, including significant bradycardia and hypotension, which can be worsened due to known side effects of propofol and dexmedetomidine. It remains unclear whether the benefits of these medications outweigh the risks in CICU patients as the use of these medications has not been studied previously in this population. This study aims to examine the use of protocol directed sedation using the Duke PAD protocol with the current sedation medications of propofol or dexmedetomidine compared to the PAD protocol with midazolam, per CICU usual care, as an initial step toward understanding the best management of sedation in these patients.
Project Aims Include:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Midazolam | Active Comparator | IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. |
|
| Propofol or Dexmedetomidine | Active Comparator | Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midazolam | Drug | IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Intensive Care Unit Length of Stay | Number of days of admission to the CICU during the index hospitalization | One month or hospital discharge, whichever time point comes first |
| Measure | Description | Time Frame |
|---|---|---|
| In Hospital Mortality | All-cause mortality during the hospitalization | One month or hospital discharge, whichever time point comes first |
| Hospital Length of Stay | Index hospitalization length of stay in days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kristin Newby, MD | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23269131 | Background | Barr J, Fraser GL, Puntillo K, Ely EW, Gelinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013 Jan;41(1):263-306. doi: 10.1097/CCM.0b013e3182783b72. | |
| 16540958 |
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No enrolled participants were excluded from the study prior to group assignment.
Patients were recruited from the Duke CICU between September 1, 2017 and June 30, 2019. Patients were identified by the rounding team for potential inclusion in the sedation trial and then screened by study team members to determine whether they met inclusion criteria. Consent was obtained from eligible patient's primary decision maker.
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| ID | Title | Description |
|---|---|---|
| FG000 | Midazolam | IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. |
| FG001 | Propofol or Dexmedetomidine | Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Midazolam | IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Intensive Care Unit Length of Stay | Number of days of admission to the CICU during the index hospitalization | Posted | Median | Inter-Quartile Range | Days | One month or hospital discharge, whichever time point comes first |
|
From time of enrollment to hospital discharge - a range of 2-29 days for the patients enrolled in the trial
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Midazolam | IV midazolam will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Midazolam: IV midazolam will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. |
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Our trial was terminated prior to goal enrollment due to difficulty with enrollment in this critically ill population of patients. The data here represent a small sample size of patients and should be viewed as pilot data for hypothesis generation.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Angela Lowenstern | Duke University | 919-684-0111 | angela.sandelin@duke.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 4, 2017 | Jun 15, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 30, 2020 | Jun 15, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D016638 | Critical Illness |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D008874 | Midazolam |
| D015742 | Propofol |
| D020927 | Dexmedetomidine |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Propofol | Drug | IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. |
|
|
| Dexmedetomidine | Drug | IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. |
|
|
| One month or hospital discharge, whichever time point comes first |
| Number of Participants With Increased Vasopressor Requirement | Patients will be monitored for increased pressor requirement during the CICU stay | One month or hospital discharge, whichever time point comes first |
| Number of Participants With Bradycardia | Patients will be monitored for bradycardia which may be associated with sedation drug. Average heart rate before, during and after use of drug will be recorded for each patient. | One month or hospital discharge, whichever time point comes first |
| Number of Ventilator Days | Days requiring mechanical ventilation during the initial episode of intubation during the hospitalization | One month or hospital discharge, whichever time point comes first |
| Number of Days From Decision to Extubate to True Extubation | The time (in days) from when the clinical care team documents a decision to pursue extubation until the time the patient was extubated | One month or hospital discharge, whichever time point comes first |
| Number of Days Alive During Admission and Free From Delirium or Coma | The number of days alive and free from delirium or coma during admission will be evaluated among patients with CAM-ICU documented | One month or hospital discharge, whichever time point comes first |
| Percentage of Time at Goal Sedation | Will use RASS (Richmond Agitation and Sedation Scale) to assess level of sedation as per standard of care by nurses in the CICU. Data that is recorded will be evaluated following discharge. The RASS ranges from -5 (unrousable) to +4 (combative) and 0 (zero) = alert and calm and goal sedation is considered a RASS level of 0 to -2. | One month or hospital discharge, whichever time point comes first |
| Time From Withdrawal of Sedation to ICU Discharge | The duration, in days, from withdrawal of sedation for mechanical ventilation until the time of discharge from the ICU | One month or hospital discharge, whichever time point comes first |
| Number of Participants With Delirium | Will use the Confusion Assessment Method for the ICU (CAM-ICU) to assess presence of delirium as per standard of care by nurses in the CICU. Patients with CAM-ICU data recorded will be included. | One month or hospital discharge, whichever time point comes first |
| Pain Management | Will use the CPOT (Critical-Care Pain Observation Tool) score to assess pain level as per standard of care by nurses in the CICU. The CPOT has a range of 0 to 8. A CPOT score of ≤ 2 = minimal to no pain present and >2 = unacceptable level of pain. Data that is recorded will be evaluated following discharge. | One month or hospital discharge, whichever time point comes first |
| Number of Participants Requiring Reintubation | Following ICU discharge, patient charts will be reviewed to evaluate whether they required reintubation. If so, will determine whether necessity of reintubation was related to delirium. | One month or hospital discharge, whichever time point comes first |
| Background |
| Carson SS, Kress JP, Rodgers JE, Vinayak A, Campbell-Bright S, Levitt J, Bourdet S, Ivanova A, Henderson AG, Pohlman A, Chang L, Rich PB, Hall J. A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients. Crit Care Med. 2006 May;34(5):1326-32. doi: 10.1097/01.CCM.0000215513.63207.7F. |
| 11296183 | Background | Hall RI, Sandham D, Cardinal P, Tweeddale M, Moher D, Wang X, Anis AH; Study Investigators. Propofol vs midazolam for ICU sedation : a Canadian multicenter randomized trial. Chest. 2001 Apr;119(4):1151-9. doi: 10.1378/chest.119.4.1151. |
| 18482144 | Background | Huey-Ling L, Chun-Che S, Jen-Jen T, Shau-Ting L, Hsing-I C. Comparison of the effect of protocol-directed sedation with propofol vs. midazolam by nurses in intensive care: efficacy, haemodynamic stability and patient satisfaction. J Clin Nurs. 2008 Jun;17(11):1510-7. doi: 10.1111/j.1365-2702.2007.02128.x. |
| 20233428 | Background | Pandharipande PP, Sanders RD, Girard TD, McGrane S, Thompson JL, Shintani AK, Herr DL, Maze M, Ely EW; MENDS investigators. Effect of dexmedetomidine versus lorazepam on outcome in patients with sepsis: an a priori-designed analysis of the MENDS randomized controlled trial. Crit Care. 2010;14(2):R38. doi: 10.1186/cc8916. Epub 2010 Mar 16. |
| 19188334 | Background | Riker RR, Shehabi Y, Bokesch PM, Ceraso D, Wisemandle W, Koura F, Whitten P, Margolis BD, Byrne DW, Ely EW, Rocha MG; SEDCOM (Safety and Efficacy of Dexmedetomidine Compared With Midazolam) Study Group. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009 Feb 4;301(5):489-99. doi: 10.1001/jama.2009.56. Epub 2009 Feb 2. |
| 9187783 | Background | Searle NR, Cote S, Taillefer J, Carrier M, Gagnon L, Roy M, Lussier D. Propofol or midazolam for sedation and early extubation following cardiac surgery. Can J Anaesth. 1997 Jun;44(6):629-35. doi: 10.1007/BF03015447. |
| 22436955 | Background | Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J; Dexmedetomidine for Long-Term Sedation Investigators. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA. 2012 Mar 21;307(11):1151-60. doi: 10.1001/jama.2012.304. |
| BG001 | Propofol or Dexmedetomidine | Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| BMI | Median | Inter-Quartile Range | kg/m^2 |
|
| Ejection Fraction | Ejection fraction (EF) is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction. | Median | Inter-Quartile Range | Percentage of blood |
|
| OG001 |
| Propofol or Dexmedetomidine |
Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. |
|
|
| Secondary | In Hospital Mortality | All-cause mortality during the hospitalization | Posted | Number | participants | One month or hospital discharge, whichever time point comes first |
|
|
|
| Secondary | Hospital Length of Stay | Index hospitalization length of stay in days | Posted | Median | Inter-Quartile Range | Days | One month or hospital discharge, whichever time point comes first |
|
|
|
| Secondary | Number of Participants With Increased Vasopressor Requirement | Patients will be monitored for increased pressor requirement during the CICU stay | Posted | Count of Participants | Participants | One month or hospital discharge, whichever time point comes first |
|
|
|
| Secondary | Number of Participants With Bradycardia | Patients will be monitored for bradycardia which may be associated with sedation drug. Average heart rate before, during and after use of drug will be recorded for each patient. | Posted | Count of Participants | Participants | One month or hospital discharge, whichever time point comes first |
|
|
|
| Secondary | Number of Ventilator Days | Days requiring mechanical ventilation during the initial episode of intubation during the hospitalization | Posted | Median | Inter-Quartile Range | Days | One month or hospital discharge, whichever time point comes first |
|
|
|
| Secondary | Number of Days From Decision to Extubate to True Extubation | The time (in days) from when the clinical care team documents a decision to pursue extubation until the time the patient was extubated | Posted | Median | Inter-Quartile Range | Days | One month or hospital discharge, whichever time point comes first |
|
|
|
| Secondary | Number of Days Alive During Admission and Free From Delirium or Coma | The number of days alive and free from delirium or coma during admission will be evaluated among patients with CAM-ICU documented | CAM-ICU was only documented in 3/7 of the patients enrolled, all of whom were in the midazolam arm of the study. Only these patients were included in this analysis. | Posted | Median | Inter-Quartile Range | Days | One month or hospital discharge, whichever time point comes first |
|
|
|
| Secondary | Percentage of Time at Goal Sedation | Will use RASS (Richmond Agitation and Sedation Scale) to assess level of sedation as per standard of care by nurses in the CICU. Data that is recorded will be evaluated following discharge. The RASS ranges from -5 (unrousable) to +4 (combative) and 0 (zero) = alert and calm and goal sedation is considered a RASS level of 0 to -2. | Posted | Median | Inter-Quartile Range | percentage of time | One month or hospital discharge, whichever time point comes first |
|
|
|
| Secondary | Time From Withdrawal of Sedation to ICU Discharge | The duration, in days, from withdrawal of sedation for mechanical ventilation until the time of discharge from the ICU | Posted | Median | Inter-Quartile Range | Days | One month or hospital discharge, whichever time point comes first |
|
|
|
| Secondary | Number of Participants With Delirium | Will use the Confusion Assessment Method for the ICU (CAM-ICU) to assess presence of delirium as per standard of care by nurses in the CICU. Patients with CAM-ICU data recorded will be included. | Patients with CAM-ICU score documented in the CICU (3/7 participants, all in the midazolam arm of the study) | Posted | Count of Participants | Participants | One month or hospital discharge, whichever time point comes first |
|
|
|
| Secondary | Pain Management | Will use the CPOT (Critical-Care Pain Observation Tool) score to assess pain level as per standard of care by nurses in the CICU. The CPOT has a range of 0 to 8. A CPOT score of ≤ 2 = minimal to no pain present and >2 = unacceptable level of pain. Data that is recorded will be evaluated following discharge. | Posted | Median | Inter-Quartile Range | score on a scale | One month or hospital discharge, whichever time point comes first |
|
|
|
| Secondary | Number of Participants Requiring Reintubation | Following ICU discharge, patient charts will be reviewed to evaluate whether they required reintubation. If so, will determine whether necessity of reintubation was related to delirium. | Posted | Count of Participants | Participants | One month or hospital discharge, whichever time point comes first |
|
|
|
| 1 |
| 4 |
| 0 |
| 4 |
| 0 |
| 4 |
| EG001 | Propofol or Dexmedetomidine | Propofol or Dexmedetomidine per physician discretion will be administered for sedation while patient is mechanically ventilated. Patient will be monitored per standard of care in the CICU using the Richmond Agitation and Sedation Scale (RASS) with a set goal sedation level of RASS 0 to -2. Pain will be monitored based on the Critical-Care Pain Observation Tool (CPOT) assessment with goal less than or equal to 2. Delirium will be evaluated based on the Confusion Assessment Method for the ICU (CAM-ICU) with goal of negative or patient's baseline. Propofol: IV propofol will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. Dexmedetomidine: IV dexmedetomidine will be administered as a continuous infusion to maintain set goal sedation level of RASS 0 to -2. | 1 | 3 | 0 | 3 | 0 | 3 |
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| D006571 | Heterocyclic Compounds |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |