Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients

Phase 4

Terminated

Conditions: Tachycardia
Septic Shock
Arrhythmia
Sepsis
Shock

Interventions: Drug: Phenylephrine
Drug: Norepinephrine

Registration Number: NCT02203630

Lead Sponsor: Vanderbilt University Medical Center

Brief Summary: 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:

1. Decreasing the mean heart rate

2. Decreasing the incidence of new tachyarrhythmias

3. Decreasing the amount of time spent in tachyarrhythmia for patients who develop new onset and recurrent tachyarrhythmias

4. Decreasing the number of cardiac complications

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 17

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phenylephrine	Phenylephrine	Phenylephrine will be administered as the primary vasopressor for the treatment of septic shock
Norepinephrine	Norepinephrine	Norepinephrine will be administered as the primary vasopressor for the treatment of septic shock

Primary Outcome Measures

Name	Time	Method
Maximum Heart Rate	Up to 28 days

Secondary Outcome Measures

Name	Time	Method
Hospital Days Not in ICU	Up to 28 days	ICU free days
Number of Days Mechanical Ventilation Needed	Up to 28 days
Number of Participants Developing Peripheral Limb Ischemia	Up to 28 days
Total Time in Arrhythmia	Up to 28 days
Number of Patients With ST-segment Abnormalities on ECG	Up to 28 days	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
Number of Participants With Arrhythmia Events	Up to 28 days
Length of Hospital Stay	Up to 28 days
Location of Death	Up to 28 days
Number of Times an Anti-arrhythmic Agent is Used	Up to 28 days
Use of Corticosteroid	Up to 28 days	number of days participants received a corticosteroid
Number of Uses of Rate-controlling Agent	Up to 28 days	includes use of Diltiazem, Esmolol, Metoprolol, Propranolol, Verapamil
Number of Direct Current (DC) Cardioversion Events	Up to 28 days
Number of Days Without Mechanical Ventilation	Up to 28 days	Mechanical ventilation-free days
Number of Days Hemodialysis Needed	Up to 28 days
Mean Sequential Organ Failure Assessment (SOFA) Score	Up to 28 days	Predicts ICU mortality based on lab results and clinical data. Range is 0-24 with higher numbers indicating a higher risk of mortality
Number of Participants With Cardiac Arrest Events	Up to 28 days
Number of Days Without Vasopressor Use	Up to 28 days	Shock free days
Days Spent Out of the Hospital	Up to 28 days	Hospital free days
Cause of Death	Up to 28 days
CK-MB	Up to 28 days	From chart review (if available)
Number of Participants Receiving Non-study Vasopressors	Up to 28 days
Amount of Time Non-study Vasopressors Used	Up to 28 days
Days Without Dialysis	Up to 28 days	Dialysis-free 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
28-day Mortality	Up to 28 days
Creatinine Kinase (CK)	Up to 28 days	From chart review (if available)
Mean Troponin-I	Up to 28 days	From chart review (if available)