Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients

• ClinicalTrials.gov Identifier: NCT02203630
• Recruitment Status: Terminated
• First Posted: July 30, 2014
• Results First Posted: June 13, 2018
• Last Update Posted: June 13, 2018
• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Center for Research Resources (NCRR); National Center for Advancing Translational Science (NCATS)
• Information provided by (Responsible Party): Vanderbilt University Medical Center

Study Description

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

Condition or disease	Intervention/treatment	Phase
Septic Shock; Sepsis; Shock; Tachycardia; Arrhythmia	Drug: Phenylephrine; Drug: Norepinephrine	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Pilot Trial of Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
• Study Start Date: August 2014
• Actual Primary Completion Date: January 2016
• Actual Study Completion Date: January 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Phenylephrine; Phenylephrine will be administered as the primary vasopressor for the treatment of septic shock	Drug: Phenylephrine; Phenylephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock; Other Name: Neosynephrine
Active Comparator: Norepinephrine; Norepinephrine will be administered as the primary vasopressor for the treatment of septic shock	Drug: Norepinephrine; Norepinephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock; Other Name: Levophed

Outcome Measures

Primary Outcome Measures :

1. Maximum Heart Rate [ Time Frame: Up to 28 days ]

Secondary Outcome Measures :

1. Number of Participants With Arrhythmia Events [ Time Frame: Up to 28 days ]
2. Total Time in Arrhythmia [ Time Frame: Up to 28 days ]
3. Number of Patients With ST-segment Abnormalities on ECG [ Time Frame: 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
4. Number of Uses of Rate-controlling Agent [ Time Frame: Up to 28 days ]
   includes use of Diltiazem, Esmolol, Metoprolol, Propranolol, Verapamil
5. Number of Times an Anti-arrhythmic Agent is Used [ Time Frame: Up to 28 days ]
6. Use of Corticosteroid [ Time Frame: Up to 28 days ]
   number of days participants received a corticosteroid
7. Number of Direct Current (DC) Cardioversion Events [ Time Frame: Up to 28 days ]
8. Number of Days Mechanical Ventilation Needed [ Time Frame: Up to 28 days ]
9. Number of Days Hemodialysis Needed [ Time Frame: Up to 28 days ]
10. Mean Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: 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
11. Number of Participants Developing Peripheral Limb Ischemia [ Time Frame: Up to 28 days ]
12. Number of Participants With Cardiac Arrest Events [ Time Frame: Up to 28 days ]
13. Number of Days Without Vasopressor Use [ Time Frame: Up to 28 days ]
    Shock free days
14. Number of Days Without Mechanical Ventilation [ Time Frame: Up to 28 days ]
    Mechanical ventilation-free days
15. Days Without Dialysis [ Time Frame: Up to 28 days ]
    Dialysis-free days
16. Hospital Days Not in ICU [ Time Frame: Up to 28 days ]
    ICU free days
17. Days Spent Out of the Hospital [ Time Frame: Up to 28 days ]
    Hospital free days
18. Readmission to ICU [ Time Frame: Up to 28 days ]
19. Number of Participants Rehospitalized After Discharge [ Time Frame: Up to 28 days ]
20. Length of ICU Stay [ Time Frame: Up to 28 days ]
21. Length of Hospital Stay [ Time Frame: Up to 28 days ]
22. 28-day Mortality [ Time Frame: Up to 28 days ]
23. Location of Death [ Time Frame: Up to 28 days ]
24. Cause of Death [ Time Frame: Up to 28 days ]
25. Mean Troponin-I [ Time Frame: Up to 28 days ]
    From chart review (if available)
26. CK-MB [ Time Frame: Up to 28 days ]
    From chart review (if available)
27. Creatinine Kinase (CK) [ Time Frame: Up to 28 days ]
    From chart review (if available)
28. Number of Participants Receiving Non-study Vasopressors [ Time Frame: Up to 28 days ]
29. Amount of Time Non-study Vasopressors Used [ Time Frame: Up to 28 days ]

Other Outcome Measures:

1. Mean Blood Pressure (Maximum and Minimum) [ Time Frame: Up to 28 days ]
2. Mean Central Venous Pressure [ Time Frame: Up to 28 days ]
3. Mean Metabolic Panel Laboratory Values [ Time Frame: Up to 28 days ]
   From chart review (if available)
4. Mean Central Venous Oxygen Saturation [ Time Frame: Up to 28 days ]
   From chart review (if available)
5. Anti-hypertensive Agents Used [ Time Frame: Up to 28 days ]
6. Diuretic Agents Used [ Time Frame: Up to 28 days ]
7. Inotropes Used [ Time Frame: Up to 28 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Vanderbilt University Medical Center

National Center for Research Resources (NCRR)

National Center for Advancing Translational Science (NCATS)

Investigators

• Principal Investigator: Raj Keriwala, MD, MPH; Vanderbilt University School of Medicine

More Information

• Responsible Party: Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT02203630
• Other Study ID Numbers: IRB 140141; UL1RR024975-01 ( U.S. NIH Grant/Contract ); UL1TR000445-06 ( U.S. NIH Grant/Contract )
• First Posted: July 30, 2014
• Results First Posted: June 13, 2018
• Last Update Posted: June 13, 2018
• Last Verified: May 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Vanderbilt University Medical Center:

Septic shock; Vasopressor Agents; Phenylephrine; Norepinephrine; Tachycardia; Heart Rate; Arrhythmia; Catecholamine

Additional relevant MeSH terms:

Shock, Septic; Arrhythmias, Cardiac; Tachycardia; Shock; Pathologic Processes; Sepsis; Infection; Systemic Inflammatory Response Syndrome; Inflammation; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Phenylephrine; Oxymetazoline; Norepinephrine; Cardiotonic Agents; Mydriatics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Sympathomimetics; Vasoconstrictor Agents; Nasal Decongestants; Respiratory System Agents; Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action