Septic ShockPhase 4NCT02203630
Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
A Phase 4 study testing Phenylephrine and Norepinephrine in people with Septic Shock and Sepsis, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Sepsis, Shock
- What is being tested?
- Phenylephrine and Norepinephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to Jan 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults 18 years of age or greater
- Intention to treat with vasopressor for diagnosis of septic shock
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: A Randomized Controlled Pilot Trial of Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
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:
Read more
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:
- Decreasing the mean heart rate
- Decreasing the incidence of new tachyarrhythmias
- Decreasing the amount of time spent in tachyarrhythmia for patients who develop new onset and recurrent tachyarrhythmias
- Decreasing the number of cardiac complications
- Conditions
- Septic Shock, Sepsis, Shock, Tachycardia, Arrhythmia
- Being tested
- Phenylephrine, Norepinephrine
- Keywords
- Septic shock, Vasopressor Agents, Phenylephrine, Norepinephrine, Tachycardia, Heart Rate, Arrhythmia, Catecholamine
- Medical subject headings
- Shock, Septic, Sepsis, Shock, Tachycardia, Arrhythmias, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhenylephrineDrug
Also called Neosynephrine
Phenylephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock
NorepinephrineDrug
Also called Levophed
Norepinephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock
| Study group | Role | What they receive |
|---|---|---|
| Phenylephrine | Active comparator | Phenylephrine will be administered as the primary vasopressor for the treatment of septic shock Receives: Drug: Phenylephrine |
| Norepinephrine | Active comparator | Norepinephrine will be administered as the primary vasopressor for the treatment of septic shock Receives: Drug: Norepinephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Heart Rate
Measured: Up to 28 days
Secondary outcomes (29)
Number of Participants With Arrhythmia Events
Measured: Up to 28 days
Total Time in Arrhythmia
Measured: Up to 28 days
Number of Patients With ST-segment Abnormalities on ECG
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
Measured: Up to 28 days
Number of Uses of Rate-controlling Agent
includes use of Diltiazem, Esmolol, Metoprolol, Propranolol, Verapamil
Measured: Up to 28 days
Number of Times an Anti-arrhythmic Agent is Used
Measured: Up to 28 days
Use of Corticosteroid
number of days participants received a corticosteroid
Measured: Up to 28 days
Number of Direct Current (DC) Cardioversion Events
Measured: Up to 28 days
Number of Days Mechanical Ventilation Needed
Measured: Up to 28 days
Number of Days Hemodialysis Needed
Measured: Up to 28 days
Mean Sequential Organ Failure Assessment (SOFA) Score
Predicts ICU mortality based on lab results and clinical data. Range is 0-24 with higher numbers indicating a higher risk of mortality
Measured: Up to 28 days
Number of Participants Developing Peripheral Limb Ischemia
Measured: Up to 28 days
Number of Participants With Cardiac Arrest Events
Measured: Up to 28 days
Number of Days Without Vasopressor Use
Shock free days
Measured: Up to 28 days
Number of Days Without Mechanical Ventilation
Mechanical ventilation-free days
Measured: Up to 28 days
Days Without Dialysis
Dialysis-free days
Measured: Up to 28 days
Hospital Days Not in ICU
ICU free days
Measured: Up to 28 days
Days Spent Out of the Hospital
Hospital free days
Measured: Up to 28 days
Readmission to ICU
Measured: Up to 28 days
Number of Participants Rehospitalized After Discharge
Measured: Up to 28 days
Length of ICU Stay
Measured: Up to 28 days
Length of Hospital Stay
Measured: Up to 28 days
28-day Mortality
Measured: Up to 28 days
Location of Death
Measured: Up to 28 days
Cause of Death
Measured: Up to 28 days
Mean Troponin-I
From chart review (if available)
Measured: Up to 28 days
CK-MB
From chart review (if available)
Measured: Up to 28 days
Creatinine Kinase (CK)
From chart review (if available)
Measured: Up to 28 days
Number of Participants Receiving Non-study Vasopressors
Measured: Up to 28 days
Amount of Time Non-study Vasopressors Used
Measured: Up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2014 (estimated)
- Study startAug 2014
- Primary completionJan 2016
- Study completionJan 2016
Why it stopped: Slow enrollment; Lack of support and equipoise
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Research Resources (NCRR), National Center for Advancing Translational Sciences (NCATS)
- Responsible party
- Sponsor
- Investigators
- Raj Keriwala, MD, MPH, Principal investigator, Vanderbilt University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02203630
- Sponsor's protocol ID
- IRB 140141
- Other IDs
- UL1RR024975-01, UL1TR000445-06
- Status last verified
- May 2018
- First submitted
- 22 Jul 2014
- Last updated
- 13 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Pilot Trial of Phenylephrine Versus Norepinephrine for Septic Shock in Critically Ill Patients
- ClinicalTrials.gov ID
- NCT02203630
- Acronym / sponsor ID
- IRB 140141
- Conditions
- Septic Shock, Sepsis, Shock, Tachycardia, Arrhythmia
- Keywords
- Septic shock, Vasopressor Agents, Phenylephrine, Norepinephrine, Tachycardia, Heart Rate, Arrhythmia, Catecholamine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment; Lack of support and equipoise
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- National Center for Research Resources (NCRR), National Center for Advancing Translational Sciences (NCATS)
- Study start
- Aug 2014
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 30 Jul 2014 (estimated)
- Results
- Posted 13 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Decreasing the mean heart rate
- Decreasing the incidence of new tachyarrhythmias
- Decreasing the amount of time spent in tachyarrhythmia for patients who develop new onset and recurrent tachyarrhythmias
- Decreasing the number of cardiac complications
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phenylephrine | Active comparator | Drug: PhenylephrinePhenylephrine will be administered as the primary vasopressor for the treatment of septic shock |
| Norepinephrine | Active comparator | Drug: NorepinephrineNorepinephrine will be administered as the primary vasopressor for the treatment of septic shock |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adults 18 years of age or greater
- Intention to treat with vasopressor for diagnosis of septic shock
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PhenylephrineAlso: NeosynephrinePhenylephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock | Drug | Phenylephrine |
| NorepinephrineAlso: LevophedNorepinephrine, in intravenous formulation, will be administered as the primary vasopressor for the treatment of septic shock | Drug | Norepinephrine |
Primary outcome
Maximum Heart Rate
Time frame: Up to 28 days
29 secondary outcomes
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
Number of Uses of Rate-controlling Agent
Time frame: Up to 28 days
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 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
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
Number of Days Without Mechanical Ventilation
Time frame: Up to 28 days
Days Without Dialysis
Time frame: Up to 28 days
Hospital Days Not in ICU
Time frame: Up to 28 days
Days Spent Out of the Hospital
Time frame: Up to 28 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
CK-MB
Time frame: Up to 28 days
Creatinine Kinase (CK)
Time frame: Up to 28 days
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Septic Shock
Not yet recruitingObservational study
Serum GDF-15 and LGALS3BP as Prognostic Biomarkers in Sepsis
Sepsis, Septic Shock
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A Trial of Adjunctive Fludrocortisone (50mcg, 100mcg or Placebo) in Critically Ill Patients With Septic Shock Receiving Hydrocortisone, Evaluating Survival and Functional Recovery and the Influence of Transcriptomic Response
Septic Shock
Recruiting
Veno-arterial Carbon Dioxide Partial Pressure Difference (CO2gap) for Early Resuscitation of Septic Shock
Sepsis - to Reduce Mortality in the Intensive Care Unit, Septic Shock
Not yet recruiting
Hemodynamic Resuscitation Guided by Non-Invasive Mean Systemic Filling Pressure to Prevent Acute Kidney Injury in Septic Shock
Acute Kidney Injury Due to Sepsis
RecruitingObservational study
Clinical Value of EMR3 in Sepsis Diagnosis, Monitoring, and Prognosis: A Multicenter Prospective Observational Study
Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raj Keriwala, MD, MPH principal investigator
Vanderbilt University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Phenylephrine and Norepinephrine in people with Septic Shock and Sepsis, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Heart Rate (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2018.