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| ID | Type | Description | Link |
|---|---|---|---|
| UL1RR024975-01 | U.S. NIH Grant/Contract | View source | |
| UL1TR000445-06 | U.S. NIH Grant/Contract | View source |
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Slow enrollment; Lack of support and equipoise
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| Name | Class |
|---|---|
| National Center for Research Resources (NCRR) | NIH |
| National Center for Advancing Translational Sciences (NCATS) | NIH |
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Septic shock is a condition that is marked by severe infection causing hypotension requiring vasopressors to maintain adequate perfusion to vital organs. The Surviving Sepsis campaign, an international organization formed for the purpose of guiding the management of sepsis and septic shock, currently recommends norepinephrine as the first-choice vasopressor for septic shock. Phenylephrine, a vasopressor FDA-approved for use in septic shock, is recommended as an alternative vasopressor when septic shock is complicated by tachyarrhythmia to mitigate cardiac complications. This recommendation is based solely on experience with no scientific evidence to support this recommendation.
The investigators will conduct an open-label randomized controlled trial (RCT) directly comparing phenylephrine and norepinephrine, two FDA-approved vasopressors that are both used in clinical practice for the management of septic shock. The investigators will perform this study with a population of patients that have septic shock to complete the following aims:
Aim 1: Determine the incidence of tachyarrhythmias.
Aim 2: Determine which vasopressor, phenylephrine or norepinephrine, is associated with a lower heart rate.
Aim 3: Determine which vasopressor, phenylephrine or norepinephrine, is associated with a higher incidence of new tachyarrhythmias.
Aim 4: Determine which vasopressor, phenylephrine or norepinephrine, is associated with less time in tachyarrhythmia.
Aim 5: Determine which vasopressor, phenylephrine or norepinephrine, is associated with fewer complications, including cardiac complications.
The investigators hypothesize that in this setting, phenylephrine will improve the management of septic shock when used as a "first choice" vasopressor by:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phenylephrine | Active Comparator | Phenylephrine will be administered as the primary vasopressor for the treatment of septic shock |
|
| Norepinephrine | Active Comparator | Norepinephrine will be administered as the primary vasopressor for the treatment of septic shock |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Phenylephrine | Drug | Phenylephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Heart Rate | Up to 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Arrhythmia Events | Up to 28 days | |
| Total Time in Arrhythmia | Up to 28 days | |
| Number of Patients With ST-segment Abnormalities on ECG |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Blood Pressure (Maximum and Minimum) | Up to 28 days | |
| Mean Central Venous Pressure | Up to 28 days | |
| Mean Metabolic Panel Laboratory Values |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Raj Keriwala, MD, MPH | Vanderbilt University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Phenylephrine | Phenylephrine will be administered as the primary vasopressor for the treatment of septic shock Phenylephrine: Phenylephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock |
| FG001 | Norepinephrine | Norepinephrine will be administered as the primary vasopressor for the treatment of septic shock Norepinephrine: Norepinephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Phenylephrine | Phenylephrine will be administered as the primary vasopressor for the treatment of septic shock Phenylephrine: Phenylephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock |
| BG001 | Norepinephrine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Maximum Heart Rate | Posted | Mean | Full Range | beats/minute | Up to 28 days |
|
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Adverse Events and Serious adverse events will not include organ failure or death that is related to septic shock, which are expected complications in this population, unless they are more severe than is expected or unusual in their happenstances.
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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 | Phenylephrine | Phenylephrine will be administered as the primary vasopressor for the treatment of septic shock Phenylephrine: Phenylephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock |
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Study was terminated early due to slow enrollment, lack of support and equipoise. PI left Vanderbilt and the record was completed with data recorded in REDCap.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Raj Keriwala | Vanderbilt University Medical Center | 615-322-3412 |
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| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| D018805 | Sepsis |
| D012769 | Shock |
| D013610 | Tachycardia |
| D001145 | Arrhythmias, Cardiac |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D010656 | Phenylephrine |
| D009638 | Norepinephrine |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| Norepinephrine | Drug | Norepinephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock |
|
|
ST Elevation of 1 mm in 2 or more consecutive leads or Horizontal or downsloping ST depression of 1 mm in 2 or more consecutive leads |
| Up to 28 days |
| Number of Uses of Rate-controlling Agent | includes use of Diltiazem, Esmolol, Metoprolol, Propranolol, Verapamil | Up to 28 days |
| Number of Times an Anti-arrhythmic Agent is Used | Up to 28 days |
| Use of Corticosteroid | number of days participants received a corticosteroid | Up to 28 days |
| Number of Direct Current (DC) Cardioversion Events | Up to 28 days |
| Number of Days Mechanical Ventilation Needed | Up to 28 days |
| Number of Days Hemodialysis Needed | Up to 28 days |
| Mean Sequential Organ Failure Assessment (SOFA) Score | Predicts ICU mortality based on lab results and clinical data. Range is 0-24 with higher numbers indicating a higher risk of mortality | Up to 28 days |
| Number of Participants Developing Peripheral Limb Ischemia | Up to 28 days |
| Number of Participants With Cardiac Arrest Events | Up to 28 days |
| Number of Days Without Vasopressor Use | Shock free days | Up to 28 days |
| Number of Days Without Mechanical Ventilation | Mechanical ventilation-free days | Up to 28 days |
| Days Without Dialysis | Dialysis-free days | Up to 28 days |
| Hospital Days Not in ICU | ICU free days | Up to 28 days |
| Days Spent Out of the Hospital | Hospital free days | Up to 28 days |
| Readmission to ICU | Up to 28 days |
| Number of Participants Rehospitalized After Discharge | Up to 28 days |
| Length of ICU Stay | Up to 28 days |
| Length of Hospital Stay | Up to 28 days |
| 28-day Mortality | Up to 28 days |
| Location of Death | Up to 28 days |
| Cause of Death | Up to 28 days |
| Mean Troponin-I | From chart review (if available) | Up to 28 days |
| CK-MB | From chart review (if available) | Up to 28 days |
| Creatinine Kinase (CK) | From chart review (if available) | Up to 28 days |
| Number of Participants Receiving Non-study Vasopressors | Up to 28 days |
| Amount of Time Non-study Vasopressors Used | Up to 28 days |
From chart review (if available) |
| Up to 28 days |
| Mean Central Venous Oxygen Saturation | From chart review (if available) | Up to 28 days |
| Anti-hypertensive Agents Used | Up to 28 days |
| Diuretic Agents Used | Up to 28 days |
| Inotropes Used | Up to 28 days |
Norepinephrine will be administered as the primary vasopressor for the treatment of septic shock Norepinephrine: Norepinephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock |
| 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 |
|
| Heart Rate | Mean | Full Range | beats/minute |
|
| Mean Blood Pressure | Mean | Full Range | mm/Hg |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Number of Participants With Arrhythmia Events | Posted | Count of Participants | Participants | Up to 28 days |
|
|
|
| Secondary | Total Time in Arrhythmia | only participants with arrhythmias included | Posted | Number | minutes | Up to 28 days |
|
|
|
| Secondary | Number of Patients With ST-segment Abnormalities on ECG | ST Elevation of 1 mm in 2 or more consecutive leads or Horizontal or downsloping ST depression of 1 mm in 2 or more consecutive leads | Posted | Count of Participants | Participants | Up to 28 days |
|
|
|
| Secondary | Number of Uses of Rate-controlling Agent | includes use of Diltiazem, Esmolol, Metoprolol, Propranolol, Verapamil | Posted | Number | number of uses | Up to 28 days |
|
|
|
| Secondary | Number of Times an Anti-arrhythmic Agent is Used | Posted | Number | events | Up to 28 days |
|
|
|
| Secondary | Use of Corticosteroid | number of days participants received a corticosteroid | Posted | Number | days | Up to 28 days |
|
|
|
| Secondary | Number of Direct Current (DC) Cardioversion Events | Posted | Number | DC cardioversion events | Up to 28 days |
|
|
|
| Secondary | Number of Days Mechanical Ventilation Needed | only participants that required mechanical ventilation | Posted | Number | days | Up to 28 days |
|
|
|
| Secondary | Number of Days Hemodialysis Needed | only participants that required dialysis | Posted | Number | days | Up to 28 days |
|
|
|
| Secondary | Mean Sequential Organ Failure Assessment (SOFA) Score | Predicts ICU mortality based on lab results and clinical data. Range is 0-24 with higher numbers indicating a higher risk of mortality | data was not collected | Posted | Up to 28 days |
|
|
| Secondary | Number of Participants Developing Peripheral Limb Ischemia | Posted | Count of Participants | Participants | Up to 28 days |
|
|
|
| Secondary | Number of Participants With Cardiac Arrest Events | Posted | Count of Participants | Participants | Up to 28 days |
|
|
|
| Secondary | Number of Days Without Vasopressor Use | Shock free days | Posted | Number | days | Up to 28 days |
|
|
|
| Secondary | Number of Days Without Mechanical Ventilation | Mechanical ventilation-free days | Posted | Number | days | Up to 28 days |
|
|
|
| Secondary | Days Without Dialysis | Dialysis-free days | Posted | Number | days | Up to 28 days |
|
|
|
| Secondary | Hospital Days Not in ICU | ICU free days | Posted | Number | days | Up to 28 days |
|
|
|
| Secondary | Days Spent Out of the Hospital | Hospital free days | Posted | Number | days | Up to 28 days |
|
|
|
| Secondary | Readmission to ICU | data was not collected | Posted | Up to 28 days |
|
|
| Secondary | Number of Participants Rehospitalized After Discharge | Posted | Count of Participants | Participants | Up to 28 days |
|
|
|
| Secondary | Length of ICU Stay | Posted | Mean | Full Range | days | Up to 28 days |
|
|
|
| Secondary | Length of Hospital Stay | Posted | Mean | Full Range | days | Up to 28 days |
|
|
|
| Secondary | 28-day Mortality | Posted | Count of Participants | Participants | Up to 28 days |
|
|
|
| Secondary | Location of Death | Posted | Count of Participants | Participants | Up to 28 days |
|
|
|
| Secondary | Cause of Death | Posted | Count of Participants | Participants | Up to 28 days |
|
|
|
| Secondary | Mean Troponin-I | From chart review (if available) | patients with troponin levels | Posted | Mean | Full Range | ng/mL | Up to 28 days |
|
|
|
| Secondary | CK-MB | From chart review (if available) | patients with CK-MB levels | Posted | Mean | Full Range | ng/mL | Up to 28 days |
|
|
|
| Secondary | Creatinine Kinase (CK) | From chart review (if available) | patients with CK levels | Posted | Mean | Full Range | units/L | Up to 28 days |
|
|
|
| Secondary | Number of Participants Receiving Non-study Vasopressors | Posted | Count of Participants | Participants | Up to 28 days |
|
|
|
| Secondary | Amount of Time Non-study Vasopressors Used | participants receiving non-study vasopressors | Posted | Number | hours | Up to 28 days |
|
|
|
| Other Pre-specified | Mean Blood Pressure (Maximum and Minimum) | Posted | Mean | Full Range | mm/Hg | Up to 28 days |
|
|
|
| Other Pre-specified | Mean Central Venous Pressure | Posted | Mean | Full Range | mm/Hg | Up to 28 days |
|
|
|
| Other Pre-specified | Mean Metabolic Panel Laboratory Values | From chart review (if available) | Not Posted | Up to 28 days | Participants |
| Other Pre-specified | Mean Central Venous Oxygen Saturation | From chart review (if available) | patients with central venous pressure readings | Posted | Mean | Full Range | mm/Hg | Up to 28 days |
|
|
|
| Other Pre-specified | Anti-hypertensive Agents Used | Not Posted | Up to 28 days | Participants |
| Other Pre-specified | Diuretic Agents Used | Not Posted | Up to 28 days | Participants |
| Other Pre-specified | Inotropes Used | Not Posted | Up to 28 days | Participants |
| 2 |
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | Norepinephrine | Norepinephrine will be administered as the primary vasopressor for the treatment of septic shock Norepinephrine: Norepinephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock | 3 | 9 | 0 | 9 | 0 | 9 |
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D000075224 | Cardiac Conduction System Disease |
| D000588 |
| Amines |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D002395 | Catecholamines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| septic shock |
|
| Hypoxemic respiratory failure |
|
| Vasopressin |
|
| Epinephrine |
|