Clinical trial NCT02203630: Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
Official title: A Randomized Controlled Pilot Trial of Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Septic Shock
Sepsis
Shock
Tachycardia
Arrhythmia
Keywords: Septic shock
Vasopressor Agents
Phenylephrine
Norepinephrine
Tachycardia
Heart Rate
Arrhythmia
Catecholamine
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Center for Research Resources (NCRR)
name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2014-07-30
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Heart Rate
timeFrame: Up to 28 days
Secondary outcomes:
measure: Number of Participants With Arrhythmia Events
timeFrame: Up to 28 days
measure: Total Time in Arrhythmia
timeFrame: Up to 28 days
measure: Number of Patients With ST-segment Abnormalities on ECG
timeFrame: Up to 28 days
measure: Number of Uses of Rate-controlling Agent
timeFrame: Up to 28 days
measure: Number of Times an Anti-arrhythmic Agent is Used
timeFrame: Up to 28 days
measure: Use of Corticosteroid
timeFrame: Up to 28 days
measure: Number of Direct Current (DC) Cardioversion Events
timeFrame: Up to 28 days
measure: Number of Days Mechanical Ventilation Needed
timeFrame: Up to 28 days
measure: Number of Days Hemodialysis Needed
timeFrame: Up to 28 days
measure: Mean Sequential Organ Failure Assessment (SOFA) Score
timeFrame: Up to 28 days
measure: Number of Participants Developing Peripheral Limb Ischemia
timeFrame: Up to 28 days
measure: Number of Participants With Cardiac Arrest Events
timeFrame: Up to 28 days
measure: Number of Days Without Vasopressor Use
timeFrame: Up to 28 days
measure: Number of Days Without Mechanical Ventilation
timeFrame: Up to 28 days
measure: Days Without Dialysis
timeFrame: Up to 28 days
measure: Hospital Days Not in ICU
timeFrame: Up to 28 days
measure: Days Spent Out of the Hospital
timeFrame: Up to 28 days
measure: Readmission to ICU
timeFrame: Up to 28 days
measure: Number of Participants Rehospitalized After Discharge
timeFrame: Up to 28 days
measure: Length of ICU Stay
timeFrame: Up to 28 days
measure: Length of Hospital Stay
timeFrame: Up to 28 days
measure: 28-day Mortality
timeFrame: Up to 28 days
measure: Location of Death
timeFrame: Up to 28 days
measure: Cause of Death
timeFrame: Up to 28 days
measure: Mean Troponin-I
timeFrame: Up to 28 days
measure: CK-MB
timeFrame: Up to 28 days
measure: Creatinine Kinase (CK)
timeFrame: Up to 28 days
measure: Number of Participants Receiving Non-study Vasopressors
timeFrame: Up to 28 days
measure: Amount of Time Non-study Vasopressors Used
timeFrame: Up to 28 days
Other outcomes:
measure: Mean Blood Pressure (Maximum and Minimum)
timeFrame: Up to 28 days
measure: Mean Central Venous Pressure
timeFrame: Up to 28 days
measure: Mean Metabolic Panel Laboratory Values
timeFrame: Up to 28 days
measure: Mean Central Venous Oxygen Saturation
timeFrame: Up to 28 days
measure: Anti-hypertensive Agents Used
timeFrame: Up to 28 days
measure: Diuretic Agents Used
timeFrame: Up to 28 days
measure: Inotropes Used
timeFrame: Up to 28 days
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University School of Medicine
name: Raj Keriwala, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: