A Phase 4 interventional study of Angiotensin II and Norepinephrine in Septic Shock, sponsored by Wake Forest University Health Sciences. Not yet recruiting at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-24.
Sponsored by Wake Forest University Health Sciences · Phase 4, Interventional, and Treatment
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.
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.
1,078 studies on the registry are indexed under Shock, Septic; 232 are open to participants now.
This study's planned enrollment of 78 is close to the median of 79 across 636 interventional studies indexed under Shock, Septic.
Browse Shock, Septic studies →Wake Forest University Health Sciences is the lead sponsor of 1,351 studies on the registry; 201 are open to participants now.
Of its 332 completed or terminated interventional studies of FDA-regulated products, 251 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
- 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
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Continuous infusion of Angiotensin II for up to 48 hours
Drug: Angiotensin II
Continuous infusion of Norepinephrine for up to 48 hours
Drug: Norepinephrine
randomized to receive Angiotensin II continuous infusion for up to 48 hours
randomized to receive Norepinephrine continuous infusion for up to 48 hours
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.
Time frame: Hour 24
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.
Time frame: 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
Time frame: Day 28
Number of Days of Vasopressor Use
Number of days without vasopressor use
Time frame: Day 28
Number of Days Without Mechanical Ventilation
Number of days without invasive mechanical ventilation
Time frame: Day 28
Number of Hours Vasopressor Free
Number of hours without requiring vasopressors during first 72 hours after randomization
Time frame: Hour 72
Number of Hours Alive
Number of hours alive during first 72 hours after randomization
Time frame: Hour 72
Number of Days Alive
Number of days alive
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Hour 24, Hour 48
Number of Participants with Acute Respiratory Distress Syndrome (ARDS)
Number of participants with ARDS
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48, Hour 72
Plasma renin activity
levels at indicated timepoints
Time frame: baseline, hour 3, hour 12, hour 24, hour 48
Prorenin
levels at indicated timepoints
Time frame: baseline, hour 3, hour 12, hour 24, hour 48
Soluble prorenin receptor (sPRR)
levels at indicated timepoints
Time frame: baseline, hour 24, hour 48
Aldosterone
levels at indicated timepoints
Time frame: baseline, hour 3, hour 12, hour 24, hour 48
Intact Aogen
levels at indicated timepoints
Time frame: baseline, hour 24, hour 48
ANG II
levels at indicated timepoints
Time frame: baseline, hour 3, hour 12, hour 24, hour 48, hour 72
Angiotensin-converting enzyme (ACE)
levels at indicated timepoints
Time frame: baseline, hour 24, hour 48
Angiotensin-converting enzyme-2 (ACE2)
levels at indicated timepoints
Time frame: baseline, hour 24, hour 48
Dipeptidyl peptidase 3 (DPP3)
levels at indicated timepoints
Time frame: baseline, hour 24, hour 48
RNA Paxgene Bulk (Bulk RNA sequencing)
levels at indicated timepoints
Time frame: baseline, hour 24, hour 48
Whole blood cryopreserved (scRNAsesq)
levels at indicated timepoints
Time frame: baseline, hour 24, hour 48
Patients with New Deep Venous Thrombosis
Number of patients with development of new deep venous thrombosis
Time frame: Day 7, Day 28
Patients with New Pulmonary Embolism
Number of patients with development of new pulmonary embolism
Time frame: Day 7, Day 28
Patients with New-Onset Atrial Fibrillation
Number of patients with new-onset atrial fibrillation
Time frame: Hour 72, day 28
Patients with New-Onset Ventricular Arrhythmias
Number of patients with new-onset ventricular arrhythmias
Time frame: Hour 72, Day 7, Day 28
Plan to share: No
No publications or documents are linked to this record.
Start is estimated for Nov 2026; primary completion for Sep 2028, 22 months later.
Of 39 non-industry phase 4 interventional studies under Shock, Septic, half reached primary completion within 24 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 38. This study's planned 22 months is close to that.
Counting every sponsor, half of 40 studies reached it within 24 months; a quarter within 16 and three quarters within 38.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Angiotensin II
Wake Forest University Health Sciences →