Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients

NCT02203630 | Terminated Phase 4 Results FDA Drug

• 3 other identifiers: IRB 140141UL1RR024975-01UL1TR000445-06
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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. 1.Decreasing the mean heart rate
2. 2.Decreasing the incidence of new tachyarrhythmias
3. 3.Decreasing the amount of time spent in tachyarrhythmia for patients who develop new onset and recurrent tachyarrhythmias
4. 4.Decreasing the number of cardiac complications

Conditions

Septic Shock; Sepsis; Shock; Tachycardia; Arrhythmia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum Heart Rate

  Up to 28 days

Secondary Outcomes (29)

• Number of Participants With Arrhythmia Events

  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

• Number of Uses of Rate-controlling Agent

  Up to 28 days

• Number of Times an Anti-arrhythmic Agent is Used

  Up to 28 days

Other Outcomes (7)

• Mean Blood Pressure (Maximum and Minimum)

  Up to 28 days

• Mean Central Venous Pressure

  Up to 28 days

• Mean Metabolic Panel Laboratory Values

  Up to 28 days

Study Arms (2)

Phenylephrine

ACTIVE COMPARATOR

Phenylephrine will be administered as the primary vasopressor for the treatment of septic shock

Drug: Phenylephrine

Norepinephrine

ACTIVE COMPARATOR

Norepinephrine will be administered as the primary vasopressor for the treatment of septic shock

Drug: Norepinephrine

Interventions

Phenylephrine DRUG

Phenylephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock

Also known as: Neosynephrine

Phenylephrine

Norepinephrine DRUG

Norepinephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock

Also known as: Levophed

Norepinephrine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults 18 years of age or greater
• Intention to treat with vasopressor for diagnosis of septic shock

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Center for Research Resources (NCRR): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Shock, Septic; Sepsis; Shock; Tachycardia; Arrhythmias, Cardiac

Interventions

Phenylephrine; Norepinephrine

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Limitations and Caveats

Study was terminated early due to slow enrollment, lack of support and equipoise. PI left Vanderbilt and the record was completed with data recorded in REDCap.

Results Point of Contact

• Title: Raj Keriwala
• Organization: Vanderbilt University Medical Center

615-322-3412

Study Officials

• Raj Keriwala, MD, MPH

  Vanderbilt University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2014
• First Posted: July 30, 2014
• Study Start: August 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: June 13, 2018
• Results First Posted: June 13, 2018

Record last verified: 2018-05

Locations

US (1)