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Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients

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ClinicalTrials.gov Identifier: NCT02203630
Recruitment Status : Terminated (Slow enrollment; Lack of support and equipoise)
First Posted : July 30, 2014
Results First Posted : June 13, 2018
Last Update Posted : June 13, 2018
Sponsor:
Collaborators:
National Center for Research Resources (NCRR)
National Center for Advancing Translational Science (NCATS)
Information provided by (Responsible Party):
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

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

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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

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




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 ]


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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02203630


Locations
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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
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Principal Investigator: Raj Keriwala, MD, MPH Vanderbilt University School of Medicine
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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    Key Record Dates
Results First Posted: June 13, 2018
Last Update Posted: June 13, 2018
Last Verified: May 2018

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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:
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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