ShockPhase 4NCT02118467
Vasoactive Drugs in Intensive Care Unit
A Phase 4 study testing Norepinephrine, Epinephrine and Phenylephrine in people with Shock, run by University of Chicago at 1 site in United States.
Trial summary
The investigators hypothesis is that for ICU patients with shock, the use of the vasoactive drugs phenylephrine and vasopressin will reduce tachydysrhythmias when compared to norepinephrine and epinephrine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Shock
- What is being tested?
- Norepinephrine, Epinephrine and Phenylephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 836 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2014to 1 Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- Age greater than or equal to 18 years old
- Requirement for vasoactive drugs via a central venous catheter for the treatment of shock. Shock will be defined as mean arterial pressure less than 70 mmHg or systolic blood pressure less than 100 mmHg despite administration of at least 1000 mL of crystalloid or 500 mL of colloid, unless there is an elevation in the central venous pressure to > 12 mmHg or in the pulmonary artery occlusion pressure to > 14 mmHg coupled with signs of tissue hypoperfusion (e.g. altered mental state, mottled skin, urine output < 0.5 mL/kg body weight for one hour, or a serum lactate level of > 2 mmol per liter).
Who cannot join
- Cardiopulmonary arrest
- Pregnancy
- Severe right heart failure
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Chicago Medical Center
Chicago, Illinois, 60637
John P Kress, MD, 773-702-6404, jkress@medicine.bsd.uchicago.edu
Anne S Pohlman, MSN, 773-702-3804, apohlman@medicine.bsd.uchicago.edu
About this study
Official title: A Randomized Double Blind Trial of Vasoactive Drugs for the Management of Shock in the ICU
The investigators hypothesis is that for ICU patients with shock, the use of the vasoactive drugs phenylephrine and vasopressin will reduce tachydysrhythmias when compared to norepinephrine and epinephrine. To investigate this hypothesis, the investigators are conducting a randomized double blind controlled trial comparing phenylephrine and vasopressin vs. norepinephrine and epinephrine in ICU patients with shock that is not responsive to IV fluids. All patients admitted to the adult intensive care units at the University of Chicago will be screened for eligibility.
Read the detailed description
Shock, defined by inadequate tissue perfusion, is a common problem in critically ill patients. Most patients who have shock have hypotension and this is typically treated initially with intravenous fluid resuscitation in patients who are fluid responsive. If patients remain hypotensive, they are typically treated with vasoactive medications. Four of the commonly used FDA approved vasoactive medications are norepinephrine, phenylephrine, epinephrine, and vasopressin. Apart from a 2010 trial comparing norepinephrine to dopamine, there are no studies to date that have shown one of the four above-mentioned vasoactive medications to be superior to another. Accordingly, choice of vasoactive medication is based upon individual physician preference, without an outcomes-related evidence base.
Two of the four above mentioned vasoactive medications (norepinephrine and epinephrine) have chronotropic effects (i.e. the tendency to increase heart rate), while the other two (phenylephrine and vasopressin) have less of a propensity to chronotropy. The potential benefits of the chronotropic effects in patients with shock (increasing cardiac output) are offset by the potential detriments (predilection to tachydysrhythmias and myocardial ischemia).
Recent evidence suggests that tachydysrhythmias are associated with worse outcomes in ICU patients. One study demonstrated that administration of the beta blocking agent esmolol improved hemodynamic outcomes and survival in patients with septic shock. It is not clear if a vasoactive drug regimen that utilizes phenylephrine and vasopressin will be associated with lower heart rates compared to a regimen that utilizes norepinephrine and epinephrine.
The investigators hypothesis is that for ICU patients with shock, the use of the vasoactive drugs phenylephrine and vasopressin will reduce tachydysrhythmias when compared to norepinephrine and epinephrine. To investigate this hypothesis, we are conducting a randomized double blind controlled trial comparing phenylephrine and vasopressin vs. norepinephrine and epinephrine in ICU patients with shock that is not responsive to IV fluids. All patients admitted to the adult intensive care units at the University of Chicago will be screened for eligibility.
Patients will be randomized to receive either phenylephrine (0.3-3.0 mcg/kg/minute), with the addition of vasopressin (0.1-0.6 milliunits/kg/minute) if a second vasopressor is required, or norepinephrine (0.03 to 0.3 mcg/kg/minute), with the addition of epinephrine (0.03 to 0.3 mcg/kg/minute) if a second vasopressor is required. These drugs will be mixed and blinded by the research pharmacy. Only the research pharmacist will know the identity of the particular vasoactive drug. As per current standard practice, the medical team in charge of the patient will determine the target blood pressure.
In either group, if two vasoactive drugs are not adequate to raise the blood pressure to the target level, open-label norepinephrine will be added. If three vasoactive drugs are inadequate to raise the blood pressure to the target level, open-label epinephrine will be added.
There will be up to a twelve-hour period from initiation of standard, non-study vasoactive support during which the patient can be consented and enrolled. This will allow the research team to contact the patient and/or family in order to obtain informed consent. Once randomized, all patients will be initiated on study drug vasoactive support at 50 percent of the maximal infusion rate. The study drug will be titrated to maintain blood pressure and the initial non-study drug will be titrated off. The primary team will direct other aspects of patient care.
We plan to examine the following pre-specified sub-groups:
- Patients who received corticosteroids during their ICU stay vs. patients who did not receive corticosteroids during their ICU stay
- Patients with depressed left ventricular ejection fraction (< 40%) vs. patients with normal left ventricular ejection fraction
- Patients with coronary artery disease vs. patients without known coronary artery disease
- Patients with different etiologies of shock (i.e. septic, cardiogenic, hypovolemic)
- Conditions
- Shock
- Being tested
- Norepinephrine, Epinephrine, Phenylephrine, Vasopressin
- Keywords
- Shock, Vasopressor agents, Norepinephrine, Epinephrine, Phenylephrine, Vasopressin, Atrial fibrillation, Tachyarrhythmia
- Medical subject headings
- Shock, Diabetes Insipidus, Atrial Fibrillation, Tachycardia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NorepinephrineDrug
Also called Levophed
Dose range 0.03 to 0.3 mcg/kg/minute, titrated to target blood pressure.
EpinephrineDrug
Dose range 0.03 to 0.3 mcg/kg/minute, titrated to target blood pressure.
PhenylephrineDrug
Also called Neo-Synephrine
Dose range 0.3 to 3.0 mcg/kg/minute, titrated to target blood pressure.
VasopressinDrug
Also called Pitressin
Dose range 0.1 to 0.6 milliunits/kg/minute, titrated to target blood pressure.
| Study group | Role | What they receive |
|---|---|---|
| Norepinephrine and epinephrine | Active comparator | Patients will receive norepinephrine infusion per standard protocol. Dose range will be 0.03-0.3 mcg/kg/minute. Norepinephrine concentration will be 16 mg/250 mL. If a second vasopressor is required, epinephrine will be added. Dose range of epinephrine will be 0.03-0.3 mcg/kg/minute. Epinephrine concentration will be 16 mg/250 mL. The drugs norepinephrine and epinephrine will be mixed and blinded by the research pharmacy. The research pharmacist will list the dose ranges in mL/hr; this will allow the bedside nurse to program the medication per standard protocol.
If the patient's shock is not adequately treated with the highest doses of both norepinephrine and epinephrine, additional, open-label norepinephrine will be added, and titrated to achieve target blood pressure. If the patient's shock is not adequately treated with three vasopressors, additional open-label epinephrine will be added, and titrated to achieve target blood pressure. Receives: Drug: Norepinephrine; Drug: Epinephrine |
| Phenylephrine and vasopressin | Active comparator | Patients will receive phenylephrine infusion per standard protocol. Dose range will be 0.3 to 3.0 mcg/kg/minute. Phenylephrine concentration will be 160 mg/250 mL. If a second vasopressor is required, vasopressin will be added. Dose range of vasopressin will be 0.1 to 0.6 milliunits/kg/minute. Vasopressin concentration will be 40 units/250 mL. The drugs phenylephrine and vasopressin will be mixed and blinded by the research pharmacy. The research pharmacist will list the dose ranges in mL/hr; this will allow the bedside nurse to program the medication per standard protocol.
If the patient's shock is not adequately treated with the highest doses of both phenylephrine and vasopressin, additional, open-label norepinephrine will be added, and titrated to achieve target blood pressure. If the patient's shock is not adequately treated with three vasopressors, additional open-label epinephrine will be added, and titrated to achieve target blood pressure. Receives: Drug: Phenylephrine; Drug: Vasopressin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hospital mortality
Measured: Six months
Secondary outcomes (2)
Heart rate
Measured: Six months
Incidence of tachydysrhythmia
Including both atrial arrhythmias (i.e. atrial fibrillation, atrial flutter) as well as ventricular dysrhythmias
Measured: SIx months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2014 (estimated)
- Study start15 May 2014
- Primary completion1 Oct 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ShockStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 836 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John P Kress, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02118467
- Sponsor's protocol ID
- 14-0047
- Status last verified
- Dec 2025
- First submitted
- 21 Mar 2014
- Last updated
- 13 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double Blind Trial of Vasoactive Drugs for the Management of Shock in the ICU
- ClinicalTrials.gov ID
- NCT02118467
- Acronym / sponsor ID
- 14-0047
- Conditions
- Shock
- Keywords
- Shock, Vasopressor agents, Norepinephrine, Epinephrine, Phenylephrine, Vasopressin, Atrial fibrillation, Tachyarrhythmia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 836 participants (estimated)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 15 May 2014 (actual)
- Primary completion
- 1 Oct 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 21 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesis is that for ICU patients with shock, the use of the vasoactive drugs phenylephrine and vasopressin will reduce tachydysrhythmias when compared to norepinephrine and epinephrine. To investigate this hypothesis, the investigators are conducting a randomized double blind controlled trial comparing phenylephrine and vasopressin vs. norepinephrine and epinephrine in ICU patients with shock that is not responsive to IV fluids. All patients admitted to the adult intensive care units at the University of Chicago will be screened for eligibility.
Detailed description
Shock, defined by inadequate tissue perfusion, is a common problem in critically ill patients. Most patients who have shock have hypotension and this is typically treated initially with intravenous fluid resuscitation in patients who are fluid responsive. If patients remain hypotensive, they are typically treated with vasoactive medications. Four of the commonly used FDA approved vasoactive medications are norepinephrine, phenylephrine, epinephrine, and vasopressin. Apart from a 2010 trial comparing norepinephrine to dopamine, there are no studies to date that have shown one of the four above-mentioned vasoactive medications to be superior to another. Accordingly, choice of vasoactive medication is based upon individual physician preference, without an outcomes-related evidence base.
Two of the four above mentioned vasoactive medications (norepinephrine and epinephrine) have chronotropic effects (i.e. the tendency to increase heart rate), while the other two (phenylephrine and vasopressin) have less of a propensity to chronotropy. The potential benefits of the chronotropic effects in patients with shock (increasing cardiac output) are offset by the potential detriments (predilection to tachydysrhythmias and myocardial ischemia).
Recent evidence suggests that tachydysrhythmias are associated with worse outcomes in ICU patients. One study demonstrated that administration of the beta blocking agent esmolol improved hemodynamic outcomes and survival in patients with septic shock. It is not clear if a vasoactive drug regimen that utilizes phenylephrine and vasopressin will be associated with lower heart rates compared to a regimen that utilizes norepinephrine and epinephrine.
The investigators hypothesis is that for ICU patients with shock, the use of the vasoactive drugs phenylephrine and vasopressin will reduce tachydysrhythmias when compared to norepinephrine and epinephrine. To investigate this hypothesis, we are conducting a randomized double blind controlled trial comparing phenylephrine and vasopressin vs. norepinephrine and epinephrine in ICU patients with shock that is not responsive to IV fluids. All patients admitted to the adult intensive care units at the University of Chicago will be screened for eligibility.
Patients will be randomized to receive either phenylephrine (0.3-3.0 mcg/kg/minute), with the addition of vasopressin (0.1-0.6 milliunits/kg/minute) if a second vasopressor is required, or norepinephrine (0.03 to 0.3 mcg/kg/minute), with the addition of epinephrine (0.03 to 0.3 mcg/kg/minute) if a second vasopressor is required. These drugs will be mixed and blinded by the research pharmacy. Only the research pharmacist will know the identity of the particular vasoactive drug. As per current standard practice, the medical team in charge of the patient will determine the target blood pressure.
In either group, if two vasoactive drugs are not adequate to raise the blood pressure to the target level, open-label norepinephrine will be added. If three vasoactive drugs are inadequate to raise the blood pressure to the target level, open-label epinephrine will be added.
There will be up to a twelve-hour period from initiation of standard, non-study vasoactive support during which the patient can be consented and enrolled. This will allow the research team to contact the patient and/or family in order to obtain informed consent. Once randomized, all patients will be initiated on study drug vasoactive support at 50 percent of the maximal infusion rate. The study drug will be titrated to maintain blood pressure and the initial non-study drug will be titrated off. The primary team will direct other aspects of patient care.
We plan to examine the following pre-specified sub-groups:
- Patients who received corticosteroids during their ICU stay vs. patients who did not receive corticosteroids during their ICU stay
- Patients with depressed left ventricular ejection fraction (< 40%) vs. patients with normal left ventricular ejection fraction
- Patients with coronary artery disease vs. patients without known coronary artery disease
- Patients with different etiologies of shock (i.e. septic, cardiogenic, hypovolemic)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Norepinephrine and epinephrine | Active comparator | Drug: Norepinephrine, Drug: EpinephrinePatients will receive norepinephrine infusion per standard protocol. Dose range will be 0.03-0.3 mcg/kg/minute. Norepinephrine concentration will be 16 mg/250 mL. If a second vasopressor is required, epinephrine will be added. Dose range of epinephrine will be 0.03-0.3 mcg/kg/minute. Epinephrine concentration will be 16 mg/250 mL. The drugs norepinephrine and epinephrine will be mixed and blinded by the research pharmacy. The research pharmacist will list the dose ranges in mL/hr; this will allow the bedside nurse to program the medication per standard protocol. If the patient's shock is not adequately treated with the highest doses of both norepinephrine and epinephrine, additional, open-label norepinephrine will be added, and titrated to achieve target blood pressure. If the patient's shock is not adequately treated with three vasopressors, additional open-label epinephrine will be added, and titrated to achieve target blood pressure. |
| Phenylephrine and vasopressin | Active comparator | Drug: Phenylephrine, Drug: VasopressinPatients will receive phenylephrine infusion per standard protocol. Dose range will be 0.3 to 3.0 mcg/kg/minute. Phenylephrine concentration will be 160 mg/250 mL. If a second vasopressor is required, vasopressin will be added. Dose range of vasopressin will be 0.1 to 0.6 milliunits/kg/minute. Vasopressin concentration will be 40 units/250 mL. The drugs phenylephrine and vasopressin will be mixed and blinded by the research pharmacy. The research pharmacist will list the dose ranges in mL/hr; this will allow the bedside nurse to program the medication per standard protocol. If the patient's shock is not adequately treated with the highest doses of both phenylephrine and vasopressin, additional, open-label norepinephrine will be added, and titrated to achieve target blood pressure. If the patient's shock is not adequately treated with three vasopressors, additional open-label epinephrine will be added, and titrated to achieve target blood pressure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age greater than or equal to 18 years old
- Requirement for vasoactive drugs via a central venous catheter for the treatment of shock. Shock will be defined as mean arterial pressure less than 70 mmHg or systolic blood pressure less than 100 mmHg despite administration of at least 1000 mL of crystalloid or 500 mL of colloid, unless there is an elevation in the central venous pressure to > 12 mmHg or in the pulmonary artery occlusion pressure to > 14 mmHg coupled with signs of tissue hypoperfusion (e.g. altered mental state, mottled skin, urine output < 0.5 mL/kg body weight for one hour, or a serum lactate level of > 2 mmol per liter).
Key exclusion criteria (3 listed)
- Cardiopulmonary arrest
- Pregnancy
- Severe right heart failure
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 |
|---|---|---|
| NorepinephrineAlso: LevophedDose range 0.03 to 0.3 mcg/kg/minute, titrated to target blood pressure. | Drug | Norepinephrine and epinephrine |
| EpinephrineDose range 0.03 to 0.3 mcg/kg/minute, titrated to target blood pressure. | Drug | Norepinephrine and epinephrine |
| PhenylephrineAlso: Neo-SynephrineDose range 0.3 to 3.0 mcg/kg/minute, titrated to target blood pressure. | Drug | Phenylephrine and vasopressin |
| VasopressinAlso: PitressinDose range 0.1 to 0.6 milliunits/kg/minute, titrated to target blood pressure. | Drug | Phenylephrine and vasopressin |
Primary outcome
Hospital mortality
Time frame: Six months
2 secondary outcomes
Heart rate
Time frame: Six months
Incidence of tachydysrhythmia
Time frame: SIx months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2026.
- Individual participant dataSharing planned: Undecided
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CAlcium and VAsopressin Following Injury Early Resuscitation (CAVALIER) Trial
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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.
John P Kress, MD principal investigator
University of Chicago
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 Norepinephrine, Epinephrine and Phenylephrine in people with Shock, run by University of Chicago 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 3 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: looking for participants now, as of the sponsor's last update on 13 Jan 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact John P Kress, MD (773-702-6404, jkress@medicine.bsd.uchicago.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hospital mortality (time frame: Six months). 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 Jan 2026.