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Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE July 22, 2014
First Posted Date  ICMJE July 30, 2014
Results First Submitted Date  ICMJE April 4, 2018
Results First Posted Date  ICMJE June 13, 2018
Last Update Posted Date June 13, 2018
Study Start Date  ICMJE August 2014
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2018)
Maximum Heart Rate [ Time Frame: Up to 28 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 28, 2014)
Mean maximum heart rate [ Time Frame: Up to 28 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2018)
  • Number of Participants With Arrhythmia Events [ Time Frame: Up to 28 days ]
  • Total Time in Arrhythmia [ Time Frame: Up to 28 days ]
  • 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
  • Number of Uses of Rate-controlling Agent [ Time Frame: Up to 28 days ]
    includes use of Diltiazem, Esmolol, Metoprolol, Propranolol, Verapamil
  • Number of Times an Anti-arrhythmic Agent is Used [ Time Frame: Up to 28 days ]
  • Use of Corticosteroid [ Time Frame: Up to 28 days ]
    number of days participants received a corticosteroid
  • Number of Direct Current (DC) Cardioversion Events [ Time Frame: Up to 28 days ]
  • Number of Days Mechanical Ventilation Needed [ Time Frame: Up to 28 days ]
  • Number of Days Hemodialysis Needed [ Time Frame: Up to 28 days ]
  • 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
  • Number of Participants Developing Peripheral Limb Ischemia [ Time Frame: Up to 28 days ]
  • Number of Participants With Cardiac Arrest Events [ Time Frame: Up to 28 days ]
  • Number of Days Without Vasopressor Use [ Time Frame: Up to 28 days ]
    Shock free days
  • Number of Days Without Mechanical Ventilation [ Time Frame: Up to 28 days ]
    Mechanical ventilation-free days
  • Days Without Dialysis [ Time Frame: Up to 28 days ]
    Dialysis-free days
  • Hospital Days Not in ICU [ Time Frame: Up to 28 days ]
    ICU free days
  • Days Spent Out of the Hospital [ Time Frame: Up to 28 days ]
    Hospital free days
  • Readmission to ICU [ Time Frame: Up to 28 days ]
  • Number of Participants Rehospitalized After Discharge [ Time Frame: Up to 28 days ]
  • Length of ICU Stay [ Time Frame: Up to 28 days ]
  • Length of Hospital Stay [ Time Frame: Up to 28 days ]
  • 28-day Mortality [ Time Frame: Up to 28 days ]
  • Location of Death [ Time Frame: Up to 28 days ]
  • Cause of Death [ Time Frame: Up to 28 days ]
  • Mean Troponin-I [ Time Frame: Up to 28 days ]
    From chart review (if available)
  • CK-MB [ Time Frame: Up to 28 days ]
    From chart review (if available)
  • Creatinine Kinase (CK) [ Time Frame: Up to 28 days ]
    From chart review (if available)
  • Number of Participants Receiving Non-study Vasopressors [ Time Frame: Up to 28 days ]
  • Amount of Time Non-study Vasopressors Used [ Time Frame: Up to 28 days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2014)
  • Number of arrhythmia events [ Time Frame: Up to 28 days ]
  • Total Time in Arrhythmia [ Time Frame: Up to 28 days ]
  • ST-segment abnormalities on ECG [ Time Frame: Up to 28 days ]
  • Use of rate-controlling agent [ Time Frame: Up to 28 days ]
  • Use of anti-arrhythmic agent [ Time Frame: Up to 28 days ]
  • Use of Corticosteroid [ Time Frame: Up to 28 days ]
  • Number of Direct Current (DC) Cardioversion Events [ Time Frame: Up to 28 days ]
  • Number of Days Mechanical Ventilation Needed [ Time Frame: Up to 28 days ]
  • Number of Days Hemodialysis Needed [ Time Frame: Up to 28 days ]
  • Mean Sequential Organ Failure Assessment score [ Time Frame: Up to 28 days ]
  • Occurrence of peripheral limb ischemia [ Time Frame: Up to 28 days ]
  • Number of cardiac arrest events [ Time Frame: Up to 28 days ]
  • Shock-free days [ Time Frame: Up to 28 days ]
  • Mechanical ventilation-free days [ Time Frame: Up to 28 days ]
  • Dialysis-free days [ Time Frame: Up to 28 days ]
  • ICU-free days [ Time Frame: Up to 28 days ]
  • Hospital-free days [ Time Frame: Up to 28 days ]
  • Readmission to ICU [ Time Frame: Up to 28 days ]
  • Rehospitalization [ Time Frame: Up to 28 days ]
  • Length of ICU Stay [ Time Frame: Up to 28 days ]
  • Length of Hospital Stay [ Time Frame: Up to 28 days ]
  • 28-day Mortality [ Time Frame: Up to 28 days ]
  • Location of Death [ Time Frame: Up to 28 days ]
  • Cause of Death [ Time Frame: Up to 28 days ]
  • Mean Troponin-I [ Time Frame: Up to 28 days ]
    From chart review (if available)
  • CK-MB [ Time Frame: Up to 28 days ]
    From chart review (if available)
  • Creatinine Kinase (CK) [ Time Frame: Up to 28 days ]
    From chart review (if available)
  • Non-study vasopressors used [ Time Frame: Up to 28 days ]
  • Amount of Time Non-study Vasopressors Used [ Time Frame: Up to 28 days ]
Current Other Pre-specified Outcome Measures
 (submitted: May 15, 2018)
  • Mean Blood Pressure (Maximum and Minimum) [ Time Frame: Up to 28 days ]
  • Mean Central Venous Pressure [ Time Frame: Up to 28 days ]
  • Mean Metabolic Panel Laboratory Values [ Time Frame: Up to 28 days ]
    From chart review (if available)
  • Mean Central Venous Oxygen Saturation [ Time Frame: Up to 28 days ]
    From chart review (if available)
  • Anti-hypertensive Agents Used [ Time Frame: Up to 28 days ]
  • Diuretic Agents Used [ Time Frame: Up to 28 days ]
  • Inotropes Used [ Time Frame: Up to 28 days ]
Original Other Pre-specified Outcome Measures
 (submitted: July 28, 2014)
  • Mean blood pressure [ Time Frame: Up to 28 days ]
  • Mean Central Venous Pressure [ Time Frame: Up to 28 days ]
  • Mean Metabolic Panel Laboratory Values [ Time Frame: Up to 28 days ]
    From chart review (if available)
  • Mean Central Venous Oxygen Saturation [ Time Frame: Up to 28 days ]
    From chart review (if available)
  • Anti-hypertensive Agents Used [ Time Frame: Up to 28 days ]
  • Diuretic Agents Used [ Time Frame: Up to 28 days ]
  • Inotropes Used [ Time Frame: Up to 28 days ]
 
Descriptive Information
Brief Title  ICMJE Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
Official Title  ICMJE A Randomized Controlled Pilot Trial of Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Septic Shock
  • Sepsis
  • Shock
  • Tachycardia
  • Arrhythmia
Intervention  ICMJE
  • Drug: Phenylephrine
    Phenylephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock
    Other Name: Neosynephrine
  • Drug: Norepinephrine
    Norepinephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock
    Other Name: Levophed
Study Arms  ICMJE
  • Active Comparator: Phenylephrine
    Phenylephrine will be administered as the primary vasopressor for the treatment of septic shock
    Intervention: Drug: Phenylephrine
  • Active Comparator: Norepinephrine
    Norepinephrine will be administered as the primary vasopressor for the treatment of septic shock
    Intervention: Drug: Norepinephrine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 15, 2018)
17
Original Estimated Enrollment  ICMJE
 (submitted: July 28, 2014)
75
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02203630
Other Study ID Numbers  ICMJE IRB 140141
UL1RR024975-01 ( U.S. NIH Grant/Contract )
UL1TR000445-06 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Vanderbilt University Medical Center
Study Sponsor  ICMJE Vanderbilt University Medical Center
Collaborators  ICMJE
  • National Center for Research Resources (NCRR)
  • National Center for Advancing Translational Science (NCATS)
Investigators  ICMJE
Principal Investigator: Raj Keriwala, MD, MPH Vanderbilt University School of Medicine
PRS Account Vanderbilt University Medical Center
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP