Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients

Study Overview
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Brief Summary
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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: Decreasing the mean heart rate Decreasing the incidence of new tachyarrhythmias Decreasing the amount of time spent in tachyarrhythmia for patients who develop new onset and recurrent tachyarrhythmias Decreasing the number of cardiac complications

Official Title
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A Randomized Controlled Pilot Trial of Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients

Conditions
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Septic Shock, Sepsis, Shock, Tachycardia, Arrhythmia

Intervention / Treatment
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* Drug: Phenylephrine
* Drug: Norepinephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults 18 years of age or greater Intention to treat with vasopressor for diagnosis of septic shock Exclusion criteria not met Exclusion Criteria: Emergent indication for surgery Patient possesses a terminal condition for which patient or medical decision maker has decided to de-escalate medical care (patients with Do Not Resuscitate order but for whom standard care is continued will not be excluded) Known allergy to phenylephrine or norepinephrine Treated with vasopressor >12 hours for current episode of shock Preference of specific vasopressor agent by patient's provider Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phenylephrine<br>Phenylephrine will be administered as the primary vasopressor for the treatment of septic shock | Drug: Phenylephrine<br>* Phenylephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock<br>* Other names: Neosynephrine;|
| Active Comparator: Norepinephrine<br>Norepinephrine will be administered as the primary vasopressor for the treatment of septic shock | Drug: Norepinephrine<br>* Norepinephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock<br>* Other names: Levophed;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Heart Rate |  | Up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tachycardia, Septic shock, Vasopressor Agents, Phenylephrine, Norepinephrine, Heart Rate, Arrhythmia, Catecholamine