Septic ShockPhase 4MANTRANCT06746753
Mechanistic Assessment of Norepinephrine Therapy vs. Angiotensin-II in Septic Shock
A Phase 4 study testing Angiotensin II and Norepinephrine in people with Septic Shock, run by Wake Forest University Health Sciences at 2 sites in United States.
Trial summary
Despite best therapy efforts, sepsis and septic shock are associated with mortality rates of up to 40%. This clinical trial will determine the benefit of exogenous Angiotensin II versus norepinephrine (conventional care) treatment in septic shock patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Angiotensin II and Norepinephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2026to 7 Oct 2028
- 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
- The presence of septic shock, defined by sepsis-3 criteria: 1-adult patients (18 years or older) with septic shock, defined by SEPSIS-3 criteria: a) suspected or known infection, b) hypotension requiring vasopressors, and c) lactate >2mmol/L 2-receiving either norepinephrine or phenylephrine with or without additional vasopressor support 3- total norepinephrine equivalent dose (NED) ≥0.1 mcg/kg/min and ≤0.5 mcg/kg/min, to maintain a MAP of at least 65 mmHg, is required for randomization 4-ability to consent and randomize within 24 hrs of first reaching NED threshold and within 48 hrs of hospital arrival
Who cannot join
- Age <18 years
- Prisoners
- Pregnant women
- Patients for whom urgent surgery is anticipated
- Leukocyte count <1,000 cells/μL
- Absolute monocyte count <200 cells/μL
Show all 10Show fewer
- Bone marrow transplant within the past 30 days
- Patients that will be withdrawing aggressive resuscitation, including withdraw of vasopressor support
- transfer from outside ICU
- history of liver cirrhosis with Child-Pugh score ≥6
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites
Massachusetts General Hospital-Harvard
Boston, Massachusetts, 02114
Michael R Filbin, MD, MS, mfilbin@mgh.harvard.edu
Daniel E Leisman, MD, dleisman@mgh.harvard.edu
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, 27157
Ashish Khanna, MD, 513-658-5866, akhanna@wakehealth.edu
Lynnette C Harris, BSN, 336-716-8791, lcharris@wakehealth.edu
About this study
Official title: Mechanistic Assessment of Norepinephrine TheRapy vs. Angiotensin-II in Septic Shock (MANTRA) Grant Submission- Dysfunctional Renin-Angiotensin System in Septic Shock
Despite best therapy efforts, sepsis and septic shock are associated with mortality rates of up to 40%. This clinical trial will determine the benefit of exogenous Angiotensin II versus norepinephrine (conventional care) treatment in septic shock patients. This trial will determine whether there are better predictors of septic shock severity. This approach may inform more appropriate treatment regimens and improve outcomes for these patients.
Read the detailed description
This study will determine whether normalization of renin-angiotensin-aldosterone system (RAAS) signaling in sepsis occurs more rapidly with treatment with Angiotensin II compared with conventional vasopressors. Trial samples will be used to identify the best RAAS biomarker predictor of treatment response via in-depth longitudinal analysis of RAAS component and to determine the extent and mechanisms of Angiotensin II impact on innate immune function during sepsis. Successful accomplishment of our aims will provide the capability to improve endotyping of septic patients by establishing the most precise and robust measurement of renin (and RAAS dysfunction). This work will improve staging and clinical precision and will facilitate the criteria for therapeutic development of targets in septic shock.
- Conditions
- Septic Shock
- Being tested
- Angiotensin II, Norepinephrine
- Keywords
- sepsis, kidney disease, intensive care
- Medical subject headings
- Shock, Septic, Sepsis, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin IIDrug
randomized to receive Angiotensin II continuous infusion for up to 48 hours
NorepinephrineDrug
randomized to receive Norepinephrine continuous infusion for up to 48 hours
| Study group | Role | What they receive |
|---|---|---|
| Angiotensin II | Experimental | Continuous infusion of Angiotensin II for up to 48 hours Receives: Drug: Angiotensin II |
| Norepinephrine | Active comparator | Continuous infusion of Norepinephrine for up to 48 hours Receives: Drug: Norepinephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Renin Level - Hour 24
Mean plasma renin level (PRA) as a measure of renin-angiotensin-aldosterone system restoration. Normal levels of active renin <1.1 pM (40 pg/mL). A level higher than normal can indicate level of shock.
Measured: Hour 24
Secondary outcomes (69)
Norepinephrine Equivalent Dose Requirement (NEE)
NEE indicates severity of shock and need for vasopressors to support blood pressure. Normal range is 0.0-1.0 mcg/kg/min. Levels above normal indicate shock and need for vasopressors. The higher the level the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48, Hour 72
Number of Days Without Renal Replacement Therapy
Number of days without renal replacement therapy
Measured: Day 28
Number of Days of Vasopressor Use
Number of days without vasopressor use
Measured: Day 28
Number of Days Without Mechanical Ventilation
Number of days without invasive mechanical ventilation
Measured: Day 28
Number of Hours Vasopressor Free
Number of hours without requiring vasopressors during first 72 hours after randomization
Measured: Hour 72
Number of Hours Alive
Number of hours alive during first 72 hours after randomization
Measured: Hour 72
Number of Days Alive
Number of days alive
Measured: Day 28
Mean Renin Level
Mean renin level as a measure of renin-angiotensin-aldosterone system restoration. Normal levels of active renin <1.1 pM (40 pg/mL). A level higher than normal can indicate level of shock.
Measured: Baseline, Hour 3, Hour 12, Hour 48, Hour 72
Sequential Organ Failure Assessment (SOFA) Score
SOFA score indicates the number and severity of failed organs and provides prognostic information on in-hospital survival in patients with severe sepsis and septic shock. Score above 0 indicates organ failure. The higher the score the more failed organs and degree of organ failure.
Measured: Baseline, Hour 24, Hour 48
APACHE-II Score
APACHE-II score assesses severity of illness in critically ill patients and indicates risk of mortality. Score range 0-10 low risk of mortality, 11-20 moderate risk, 21-30 high risk, 31 or above very high risk.
Measured: Baseline, Hour 24, Hour 48
Lactate Level
Lactate is an indicator of sepsis severity. Levels 2.3-20 mmol/L indicate sepsis. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48, Hour 72
Kidney Disease Improving Global Outcomes (KDIGO) Stage
Participant stage of acute kidney injury will be determined as follows Stage 1: Increase in serum creatinine ≥ 0.3 mg/dL in 48 hours or 1.5 to 1.9 multiplied by baseline (in 7 days); Stage 2: 2.0 to 2.9 multiplied by baseline serum creatinine; Stage 3: 3.0 or more multiplied by baseline; increase in serum creatinine ≥ 4.0 mg/dL; or beginning of renal replacement therapy regardless of a previous KDIGO stage. Higher stage indicates higher severity of renal failure.
Measured: Baseline, Hour 24, Hour 48
Creatinine Level
Creatinine level is an indicator of renal disease severity. Normal range for women 0.7-1.3 mg/dL, men 0.6-1.1 mg/dL. Levels higher than normal indicate renal disease. The higher the level the more severe.
Measured: Baseline, Hour 24, Hour 48
BUN Level
BUN level is an indicator of renal disease severity. Levels above 24 mg/dL indicate renal disease. The higher the level the more severe.
Measured: Baseline, Hour 24, Hour 48
Bicarbonate Level
Bicarbonate level is an indicator of acid base disturbance severity. Normal range is 22-29 mEq/L. Levels above or below the normal range indicate acid base disturbance. The higher the score the more severe.
Measured: Baseline, Hour 24, Hour 48
Number of Participants with Acute Respiratory Distress Syndrome (ARDS)
Number of participants with ARDS
Measured: Baseline, Hour 24, Hour 48
SpO2/FiO2 Ratio Level
SpO2/FiO2 ratio level is an indicator of lung injury severity. Mild severity 315-235, moderate severity 148-235, severe <148.
Measured: Baseline, Hour 24, Hour 48
PaO2/FiO2 Ratio Level
PaO2/FiO2 ratio level is an indicator of lung injury severity. Mild severity 201-300 mmHg; moderate severity 101-200 mmHg, severe ≤ 100 mmHg.
Measured: Baseline, Hour 24, Hour 48
Serum Aspartate Aminotransferases Level
Serum aspartate aminotransferases level is an indicator of liver injury severity. Normal range 8-48 U/L. Levels above normal indicate livery injury. The higher the level the more severe.
Measured: Baseline, Hour 24, Hour 48
Alanine Aminotransferases Level
Alanine aminotransferases level is indicator of liver injury severity. Normal range 7-55 U/L. Levels higher than normal indicate liver injury. The higher the level the more severe.
Measured: Baseline, Hour 24, Hour 48
Alkaline Phosphatase Level
Alkaline phosphatase level is an indicator of liver injury severity. Normal range 40-129 U/L. Levels higher than normal indicate liver injury. The higher the level the more severe.
Measured: Baseline, Hour 24, Hour 48
Bilirubin Level
Bilirubin level is an indicator of liver injury severity. Normal range 0.1-1.2 mg/dL. Levels higher than normal indicate liver injury. The higher the liver the more severe.
Measured: Baseline, Hour 24, Hour 48
Albumin Level
Albumin level is an indicator of liver injury severity. Normal range 3.5-5.0 g/dL. Levels higher than normal indicate liver injury. The higher the level the more severe.
Measured: Baseline, Hour 24, Hour 48
Troponin I Level
Troponin I level is an indicator of cardiac myocyte injury. Normal range 0-0.04 ng/mL. Levels higher than normal indicate cardiac myocyte injury. The higher the level the more severe.
Measured: Baseline, Hour 24, Hour 48
Troponin T Level
Troponin T level is an indicator of cardiac myocyte injury. Normal range 0-0.01 ng/mL. Levels higher than normal indicate cardiac myocyte injury. The higher the level the more severe.
Measured: Baseline, Hour 24, Hour 48
Neutrophil Gelatinase-Associated Lipocalin Serum Level
Neutrophil gelatinase-associated lipocalin serum level indicates risk of kidney injury. Normal serum level is <10 mcg/L. Levels higher than normal indicate risk of kidney injury.
Measured: Baseline, Hour 24, Hour 48
Neutrophil Gelatinase-Associated Lipocalin Urine Level
Neutrophil gelatinase-associated lipocalin urine level indicates risk of kidney injury. Normal urine level is ≤50 ng/ml. Risk of kidney disease: Low risk 51-149 ng/ml, moderate risk 150-299 ng/ml, and high risk ≥300 ng/ml.
Measured: Baseline, Hour 24, Hour 48
Kidney Injury Molecule-I Urine Level
Kidney injury molecule-I urine level is used to detect kidney injury. Normal level is <1 ng/ml. Levels higher than normal indicate ischemic kidney injury.
Measured: Baseline, Hour 24, Hour 48
Kidney Injury Molecule-I Blood Level
Kidney injury molecule-I blood level is used to detect kidney injury. Normal levels 0.42-2.0 ng/ml. Levels higher than normal indicate kidney injury. The higher the level the more severe.
Measured: Baseline, Hour 24, Hour 48
Soluble Receptor for Advanced Glycation End Product Level
Soluble receptor for advanced glycation end product level is a marker of aging, hypertension and diabetes. Normal range is 647-1248 pg/ml. Levels higher than normal indicate risk for hypertension and diabetes.
Measured: Baseline, Hour 24, Hour 48
Angiopoietin-2 Level
Angiopoietin-2 level is a marker of inflammation. Normal range is 1434-4141 pg/mL. Levels higher than normal indicate inflammation.
Measured: Baseline, Hour 24, Hour 48, Hour 72
Syndecan-1 Level
Syndecan-1 level is a marker of disease severity in critically ill patients. Levels >20ng/ml indicate severe disease. The higher the level the more severe.
Measured: Baseline, Hour 24, Hour 48
Protein C Level
Protein C level is an indicator of inflammation and thrombotic state. Normal level is <8 mg/L. Levels higher than normal indicate inflammation and thrombotic state. The higher the level the more severe.
Measured: Baseline, Hour 24, Hour 48
Neuron-Specific Enolase Level
Neuron-specific enolase level is an indicator of brain injury. Normal range is 16-17 ug/L. Levels higher than normal indicate brain injury. The higher the level the more severe.
Measured: Baseline, Hour 24, Hour 48
S-100β Level
S-100β level is indicator of brain injury. Normal range is 0.02-0.05 μg/dL. Levels higher than normal indicate brain injury. The higher the number the more severe.
Measured: Baseline, Hour 24, Hour 48
TNFα Level
TNFα level is an indicator of systemic inflammation. Normal levels are 75 +/- 15 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
sTNFR1 Level
sTNFR1 level is an indicator of systemic inflammation. Normal levels are <2.4 ng/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
IL-6 Level
IL-6 level is an indicator of systemic inflammation. Normal range is 0-43.5 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
sIL-6R Level
sIL-6R level is an indicator of systemic inflammation. Normal range is 14-46 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
IL-8 Level
IL-8 level is an indicator of systemic inflammation. Normal range is 0-66.1 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
IL-1β Level
IL-1β level is an indicator of systemic inflammation. Normal range is 0.5-12 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
Interferon Gamma Level
IFN-ɣ level is an indicator of systemic inflammation. Normal range is 0-8.6 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
IL12p70 Level
IL12p70 level is an indicator of systemic inflammation. Normal range is 0-1.9 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
IL-17 Level
IL-17 level is an indicator of systemic inflammation. Normal range is 0-1.4 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
MIP1-alpha Level
MIP1-αlpha level is an indicator of systemic inflammation. Normal range is 0-208 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
MIP1-beta Level
MIP1-beta level is an indicator of systemic inflammation. Normal range is 59-647 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
IP-10 Level
IP-10 level is an indicator of systemic inflammation. Normal range is 4.8-9.8 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
IL-10 Level
IL-10 level is an indicator of systemic inflammation. Normal range is 4.8-9.8 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
IL-1RA Level
IL-1RA level is an indicator of systemic inflammation. Normal range is 100-300 ng/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
IL-12p40 Level
IL-12p40 level is an indicator of systemic inflammation. Normal range is 0.064-1000 pg/ml. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
C reactive protein (CRP) Level
CRP level is an indicator of systemic inflammation. Normal range is 0-10 mg/dl. Levels higher than normal indicate inflammation. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
Procalcitonin Level
Procalcitonin level is an indicator of systemic inflammation. Levels >0.25 mg/ml indicate inflammation and infection. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
Platelet Level
Platelet level is an indicator of systemic inflammation and thrombocytosis. Normal range is 150000-450000 platelets per microliter. Levels higher than normal indicate inflammation and thrombocytosis. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
Absolute Neutrophil Count Level
Absolute neutrophil count level is an indicator of inflammation and infection/sepsis. Normal range is 2500-7000 neutrophils per microliter. Levels higher than normal indicate inflammation, infection/sepsis. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
Absolute Granulocyte Count Level
Absolute granulocyte count level is an indicator of inflammation and infection/sepsis. Normal range is 1500-8500 granulocytes per microliter. Levels higher than normal indicate inflammation, infection/sepsis. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
Absolute Lymphocytes Count Level
Absolute lymphocyte count level is an indicator of inflammation and infection/sepsis. Normal range is 1000-4800 granulocytes per microliter. Levels higher than normal indicate inflammation, infection/sepsis. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
Neutrophil-Lymphocyte Ratio Level
Neutrophil-lymphocyte ratio level is an indicator of inflammation and infection/sepsis or marrow malignancy. Normal range is 1-2. Levels higher than normal indicate inflammation, infection/sepsis, marrow malignancy. The higher the score the more severe.
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
Angiotensin (1-7)
Angiotensin (1-7) level as a measure of the renin-angiotensin-aldosterone system
Measured: Baseline, Hour 3, Hour 12, Hour 24, Hour 48, Hour 72
Plasma renin activity
levels at indicated timepoints
Measured: baseline, hour 3, hour 12, hour 24, hour 48
Prorenin
levels at indicated timepoints
Measured: baseline, hour 3, hour 12, hour 24, hour 48
Soluble prorenin receptor (sPRR)
levels at indicated timepoints
Measured: baseline, hour 24, hour 48
Aldosterone
levels at indicated timepoints
Measured: baseline, hour 3, hour 12, hour 24, hour 48
Intact Aogen
levels at indicated timepoints
Measured: baseline, hour 24, hour 48
ANG II
levels at indicated timepoints
Measured: baseline, hour 3, hour 12, hour 24, hour 48, hour 72
Angiotensin-converting enzyme (ACE)
levels at indicated timepoints
Measured: baseline, hour 24, hour 48
Angiotensin-converting enzyme-2 (ACE2)
levels at indicated timepoints
Measured: baseline, hour 24, hour 48
Dipeptidyl peptidase 3 (DPP3)
levels at indicated timepoints
Measured: baseline, hour 24, hour 48
RNA Paxgene Bulk (Bulk RNA sequencing)
levels at indicated timepoints
Measured: baseline, hour 24, hour 48
Whole blood cryopreserved (scRNAsesq)
levels at indicated timepoints
Measured: baseline, hour 24, hour 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2024
- Study startNov 2026 (estimated)
- Primary completion30 Sep 2028 (estimated)
- Study completion7 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe 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
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Ashish Khanna, MD, Principal investigator, Atrium Health Wake Forest Baptist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06746753
- Sponsor's protocol ID
- IRB00115287
- Other IDs
- R01HL177834
- Acronym
- MANTRA
- Status last verified
- Jun 2026
- First submitted
- 18 Dec 2024
- Last updated
- 24 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Assessment of Norepinephrine TheRapy vs. Angiotensin-II in Septic Shock (MANTRA) Grant Submission- Dysfunctional Renin-Angiotensin System in Septic Shock
- ClinicalTrials.gov ID
- NCT06746753
- Acronym / sponsor ID
- MANTRA / IRB00115287
- Conditions
- Septic Shock
- Keywords
- sepsis, kidney disease, intensive care
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Nov 2026 (estimated)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 7 Oct 2028 (estimated)
- First posted
- 24 Dec 2024 (actual)
- 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.
Despite best therapy efforts, sepsis and septic shock are associated with mortality rates of up to 40%. This clinical trial will determine the benefit of exogenous Angiotensin II versus norepinephrine (conventional care) treatment in septic shock patients. This trial will determine whether there are better predictors of septic shock severity. This approach may inform more appropriate treatment regimens and improve outcomes for these patients.
Detailed description
This study will determine whether normalization of renin-angiotensin-aldosterone system (RAAS) signaling in sepsis occurs more rapidly with treatment with Angiotensin II compared with conventional vasopressors. Trial samples will be used to identify the best RAAS biomarker predictor of treatment response via in-depth longitudinal analysis of RAAS component and to determine the extent and mechanisms of Angiotensin II impact on innate immune function during sepsis. Successful accomplishment of our aims will provide the capability to improve endotyping of septic patients by establishing the most precise and robust measurement of renin (and RAAS dysfunction). This work will improve staging and clinical precision and will facilitate the criteria for therapeutic development of targets in septic shock.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Angiotensin II | Experimental | Drug: Angiotensin IIContinuous infusion of Angiotensin II for up to 48 hours |
| Norepinephrine | Active comparator | Drug: NorepinephrineContinuous infusion of Norepinephrine for up to 48 hours |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- The presence of septic shock, defined by sepsis-3 criteria: 1-adult patients (18 years or older) with septic shock, defined by SEPSIS-3 criteria: a) suspected or known infection, b) hypotension requiring vasopressors, and c) lactate >2mmol/L 2-receiving either norepinephrine or phenylephrine with or without additional vasopressor support 3- total norepinephrine equivalent dose (NED) ≥0.1 mcg/kg/min and ≤0.5 mcg/kg/min, to maintain a MAP of at least 65 mmHg, is required for randomization 4-ability to consent and randomize within 24 hrs of first reaching NED threshold and within 48 hrs of hospital arrival
Key exclusion criteria (10 listed)
- Age <18 years
- Prisoners
- Pregnant women
- Patients for whom urgent surgery is anticipated
- Leukocyte count <1,000 cells/μL
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 |
|---|---|---|
| Angiotensin IIrandomized to receive Angiotensin II continuous infusion for up to 48 hours | Drug | Angiotensin II |
| Norepinephrinerandomized to receive Norepinephrine continuous infusion for up to 48 hours | Drug | Norepinephrine |
Primary outcome
Mean Renin Level - Hour 24
Time frame: Hour 24
Mean plasma renin level (PRA) as a measure of renin-angiotensin-aldosterone system restoration. Normal levels of active renin <1.1 pM (40 pg/mL). A level higher than normal can indicate level of shock.
69 secondary outcomes
Norepinephrine Equivalent Dose Requirement (NEE)
Time frame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48, Hour 72
Number of Days Without Renal Replacement Therapy
Time frame: Day 28
Number of Days of Vasopressor Use
Time frame: Day 28
Number of Days Without Mechanical Ventilation
Time frame: Day 28
Number of Hours Vasopressor Free
Time frame: Hour 72
Number of Hours Alive
Time frame: Hour 72
Number of Days Alive
Time frame: Day 28
Mean Renin Level
Time frame: Baseline, Hour 3, Hour 12, Hour 48, Hour 72
Sequential Organ Failure Assessment (SOFA) Score
Time frame: Baseline, Hour 24, Hour 48
APACHE-II Score
Time frame: Baseline, Hour 24, Hour 48
Lactate Level
Time frame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48, Hour 72
Kidney Disease Improving Global Outcomes (KDIGO) Stage
Time frame: Baseline, Hour 24, Hour 48
Creatinine Level
Time frame: Baseline, Hour 24, Hour 48
BUN Level
Time frame: Baseline, Hour 24, Hour 48
Bicarbonate Level
Time frame: Baseline, Hour 24, Hour 48
Number of Participants with Acute Respiratory Distress Syndrome (ARDS)
Time frame: Baseline, Hour 24, Hour 48
SpO2/FiO2 Ratio Level
Time frame: Baseline, Hour 24, Hour 48
PaO2/FiO2 Ratio Level
Time frame: Baseline, Hour 24, Hour 48
Serum Aspartate Aminotransferases Level
Time frame: Baseline, Hour 24, Hour 48
Alanine Aminotransferases Level
Time frame: Baseline, Hour 24, Hour 48
Alkaline Phosphatase Level
Time frame: Baseline, Hour 24, Hour 48
Bilirubin Level
Time frame: Baseline, Hour 24, Hour 48
Albumin Level
Time frame: Baseline, Hour 24, Hour 48
Troponin I Level
Time frame: Baseline, Hour 24, Hour 48
Troponin T Level
Time frame: Baseline, Hour 24, Hour 48
Neutrophil Gelatinase-Associated Lipocalin Serum Level
Time frame: Baseline, Hour 24, Hour 48
Neutrophil Gelatinase-Associated Lipocalin Urine Level
Time frame: Baseline, Hour 24, Hour 48
Kidney Injury Molecule-I Urine Level
Time frame: Baseline, Hour 24, Hour 48
Kidney Injury Molecule-I Blood Level
Time frame: Baseline, Hour 24, Hour 48
Soluble Receptor for Advanced Glycation End Product Level
Time frame: Baseline, Hour 24, Hour 48
Angiopoietin-2 Level
Time frame: Baseline, Hour 24, Hour 48, Hour 72
Syndecan-1 Level
Time frame: Baseline, Hour 24, Hour 48
Protein C Level
Time frame: Baseline, Hour 24, Hour 48
Neuron-Specific Enolase Level
Time frame: Baseline, Hour 24, Hour 48
S-100β Level
Time frame: Baseline, Hour 24, Hour 48
TNFα Level
Time frame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
sTNFR1 Level
Time frame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
IL-6 Level
Time frame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
sIL-6R Level
Time frame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
IL-8 Level
Time frame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
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 24 Sep 2026.
- Individual participant dataSharing planned: No
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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.
Ashish Khanna, MD principal investigator
Atrium Health Wake Forest Baptist
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Angiotensin II and Norepinephrine in people with Septic Shock, run by Wake Forest University Health Sciences at 2 sites 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 1 inclusion and 10 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: opening soon, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 Ashish Khanna, MD (513-658-5866, ashish.khanna@wfusm.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Renin Level - Hour 24 (time frame: Hour 24). 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 24 Sep 2026.