Trial Outcomes & Findings for Serum Biomarkers to Predict Response to Angiotensin II in Septic Shock (NCT NCT05824767)
NCT ID: NCT05824767
Last Updated: 2026-07-02
Results Overview
BP response will be assessed at 3 hours in both groups and measured using NED. The primary outcome will be ability of baseline renin (obtained at drug initiation or equivalent SOC timepoint) to predict total NED at 3 hours, stratified by treatment arm (AngII vs. SOC) and adjusted for baseline Sequential Organ Failure Assessment (SOFA) scores. Shown are beta-coefficients from linear regression analyses between baseline levels of each biomarker and change in NED at 3 hours, adjusted for baseline SOFA score. NED shown is as defined by Goradia et al. J Crit Care. 2021;61:233-240 and See et al. J Crit Care. 2024;79:154453.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
42 participants
Primary outcome timeframe
3 hours post drug initiation or SOC equivalent
Results posted on
2026-07-02
Participant Flow
Two subjects were excluded after consent and randomization but before study start. See below for details.
Participant milestones
| Measure |
Angiotensin II
For patients randomized to the intervention group, once the dose of background norepinephrine reaches ≥0.10 mcg/kg/min for ≥30 minutes, angiotensin II will be started at a dose of 20 ng/kg/min (recommended starting dose in package insert).Thereafter, angiotensin II and norepinephrine will both be titrated to mean arterial pressure (MAP) goal of \>/= 65 mmHg according to the protocol titration scheme and in accordance with the University of New Mexico Hospital (UNMH) Nursing Department Titration Guideline. Angiotensin II treatment will be capped at 72 hours, at which point (if a second vasopressor is still needed) the patient will be started on an alternative agent.
|
Standard of Care (SOC)
Vasopressor therapy be titrated by the clinical team per usual SOC and UNMH Nursing Department Titration Guideline. using other available vasopressor agents (e.g., higher-dose norepinephrine, vasopressin, epinephrine, phenylephrine, and/or dopamine). To provide a comparator arm, patients in the SOC will have renin and DPP3 levels obtained at equivalent timepoints.
|
|---|---|---|
|
Overall Study
STARTED
|
21
|
21
|
|
Overall Study
COMPLETED
|
20
|
20
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Angiotensin II
For patients randomized to the intervention group, once the dose of background norepinephrine reaches ≥0.10 mcg/kg/min for ≥30 minutes, angiotensin II will be started at a dose of 20 ng/kg/min (recommended starting dose in package insert).Thereafter, angiotensin II and norepinephrine will both be titrated to mean arterial pressure (MAP) goal of \>/= 65 mmHg according to the protocol titration scheme and in accordance with the University of New Mexico Hospital (UNMH) Nursing Department Titration Guideline. Angiotensin II treatment will be capped at 72 hours, at which point (if a second vasopressor is still needed) the patient will be started on an alternative agent.
|
Standard of Care (SOC)
Vasopressor therapy be titrated by the clinical team per usual SOC and UNMH Nursing Department Titration Guideline. using other available vasopressor agents (e.g., higher-dose norepinephrine, vasopressin, epinephrine, phenylephrine, and/or dopamine). To provide a comparator arm, patients in the SOC will have renin and DPP3 levels obtained at equivalent timepoints.
|
|---|---|---|
|
Overall Study
Patient developed chest pain after consent but before study start; excluded for safety.
|
1
|
0
|
|
Overall Study
No longer met inclusion criteria (unanticipated resolution of vasopressor need before study start).
|
0
|
1
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Angiotensin II
n=20 Participants
For patients randomized to the intervention group, once the dose of background norepinephrine reaches ≥0.10 mcg/kg/min for ≥30 minutes, angiotensin II will be started at a dose of 20 ng/kg/min (recommended starting dose in package insert).Thereafter, angiotensin II and norepinephrine will both be titrated to mean arterial pressure (MAP) goal of \>/= 65 mmHg according to the protocol titration scheme and in accordance with the University of New Mexico Hospital (UNMH) Nursing Department Titration Guideline. Angiotensin II treatment will be capped at 72 hours, at which point (if a second vasopressor is still needed) the patient will be started on an alternative agent.
|
Standard of Care (SOC)
n=20 Participants
Vasopressor therapy be titrated by the clinical team per usual SOC and UNMH Nursing Department Titration Guideline. using other available vasopressor agents (e.g., higher-dose norepinephrine, vasopressin, epinephrine, phenylephrine, and/or dopamine). To provide a comparator arm, patients in the SOC will have renin and DPP3 levels obtained at equivalent timepoints.
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70.5 years
n=20 Participants
|
64.5 years
n=20 Participants
|
68.5 years
n=40 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=20 Participants
|
9 Participants
n=20 Participants
|
25 Participants
n=40 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=20 Participants
|
11 Participants
n=20 Participants
|
15 Participants
n=40 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Baseline SOFA score
|
9 units on a scale
n=20 Participants
|
8.5 units on a scale
n=20 Participants
|
9 units on a scale
n=40 Participants
|
PRIMARY outcome
Timeframe: 3 hours post drug initiation or SOC equivalentBP response will be assessed at 3 hours in both groups and measured using NED. The primary outcome will be ability of baseline renin (obtained at drug initiation or equivalent SOC timepoint) to predict total NED at 3 hours, stratified by treatment arm (AngII vs. SOC) and adjusted for baseline Sequential Organ Failure Assessment (SOFA) scores. Shown are beta-coefficients from linear regression analyses between baseline levels of each biomarker and change in NED at 3 hours, adjusted for baseline SOFA score. NED shown is as defined by Goradia et al. J Crit Care. 2021;61:233-240 and See et al. J Crit Care. 2024;79:154453.
Outcome measures
| Measure |
Standard of Care (SOC)
n=20 Participants
Vasopressor therapy be titrated by the clinical team per usual SOC and UNMH Nursing Department Titration Guideline. using other available vasopressor agents (e.g., higher-dose norepinephrine, vasopressin, epinephrine, phenylephrine, and/or dopamine). To provide a comparator arm, patients in the SOC will have renin and DPP3 levels obtained at equivalent timepoints.
|
Angiotensin II
n=20 Participants
For patients randomized to the intervention group, once the dose of background norepinephrine reaches ≥0.10 mcg/kg/min for ≥30 minutes, angiotensin II will be started at a dose of 20 ng/kg/min (recommended starting dose in package insert).Thereafter, angiotensin II and norepinephrine will both be titrated to mean arterial pressure (MAP) goal of \>/= 65 mmHg according to the protocol titration scheme and in accordance with the University of New Mexico Hospital (UNMH) Nursing Department Titration Guideline. Angiotensin II treatment will be capped at 72 hours, at which point (if a second vasopressor is still needed) the patient will be started on an alternative agent.
|
|---|---|---|
|
Ability of Baseline Active Renin to Predict Norepinephrine Equivalent Dose (NED) at 3 Hours
|
0.004 ng/kg/min of NED per pg/mL of renin
Interval -0.05 to 0.06
|
0.14 ng/kg/min of NED per pg/mL of renin
Interval -0.17 to 0.46
|
PRIMARY outcome
Timeframe: 3 hours post drug initiation or SOC equivalentBP response will be assessed at 3 hours in both groups and measured using NED. The primary outcome will be ability of baseline DPP3 (obtained at drug initiation or equivalent SOC timepoint) to predict total NED at 3 hours, stratified by treatment arm (AngII vs. SOC) and adjusted for baseline Sequential Organ Failure Assessment (SOFA) scores. Shown are beta-coefficients from linear regression analyses between baseline levels of each biomarker and change in NED at 3 hours, adjusted for baseline SOFA score. NED shown is as defined by Goradia et al. J Crit Care. 2021;61:233-240 and See et al. J Crit Care. 2024;79:154453.
Outcome measures
| Measure |
Standard of Care (SOC)
n=20 Participants
Vasopressor therapy be titrated by the clinical team per usual SOC and UNMH Nursing Department Titration Guideline. using other available vasopressor agents (e.g., higher-dose norepinephrine, vasopressin, epinephrine, phenylephrine, and/or dopamine). To provide a comparator arm, patients in the SOC will have renin and DPP3 levels obtained at equivalent timepoints.
|
Angiotensin II
n=20 Participants
For patients randomized to the intervention group, once the dose of background norepinephrine reaches ≥0.10 mcg/kg/min for ≥30 minutes, angiotensin II will be started at a dose of 20 ng/kg/min (recommended starting dose in package insert).Thereafter, angiotensin II and norepinephrine will both be titrated to mean arterial pressure (MAP) goal of \>/= 65 mmHg according to the protocol titration scheme and in accordance with the University of New Mexico Hospital (UNMH) Nursing Department Titration Guideline. Angiotensin II treatment will be capped at 72 hours, at which point (if a second vasopressor is still needed) the patient will be started on an alternative agent.
|
|---|---|---|
|
Ability of Baseline DPP3 to Predict NED at 3 Hours
|
-0.5 NED in mcg/kg/min per ng/mL of DPP3
Interval -1.1 to 0.1
|
2.6 NED in mcg/kg/min per ng/mL of DPP3
Interval 1.0 to 4.1
|
SECONDARY outcome
Timeframe: Until hospital discharge or 28 days post-randomization.Death before hospital discharge. Specified as a key secondary outcome.
Outcome measures
| Measure |
Standard of Care (SOC)
n=20 Participants
Vasopressor therapy be titrated by the clinical team per usual SOC and UNMH Nursing Department Titration Guideline. using other available vasopressor agents (e.g., higher-dose norepinephrine, vasopressin, epinephrine, phenylephrine, and/or dopamine). To provide a comparator arm, patients in the SOC will have renin and DPP3 levels obtained at equivalent timepoints.
|
Angiotensin II
n=20 Participants
For patients randomized to the intervention group, once the dose of background norepinephrine reaches ≥0.10 mcg/kg/min for ≥30 minutes, angiotensin II will be started at a dose of 20 ng/kg/min (recommended starting dose in package insert).Thereafter, angiotensin II and norepinephrine will both be titrated to mean arterial pressure (MAP) goal of \>/= 65 mmHg according to the protocol titration scheme and in accordance with the University of New Mexico Hospital (UNMH) Nursing Department Titration Guideline. Angiotensin II treatment will be capped at 72 hours, at which point (if a second vasopressor is still needed) the patient will be started on an alternative agent.
|
|---|---|---|
|
Hospital Mortality
|
5 Participants
|
3 Participants
|
Adverse Events
Angiotensin II
Serious events: 2 serious events
Other events: 18 other events
Deaths: 3 deaths
Standard of Care (SOC)
Serious events: 1 serious events
Other events: 18 other events
Deaths: 5 deaths
Serious adverse events
| Measure |
Angiotensin II
n=20 participants at risk
For patients randomized to the intervention group, once the dose of background norepinephrine reaches ≥0.10 mcg/kg/min for ≥30 minutes, angiotensin II will be started at a dose of 20 ng/kg/min (recommended starting dose in package insert).Thereafter, angiotensin II and norepinephrine will both be titrated to mean arterial pressure (MAP) goal of \>/= 65 mmHg according to the protocol titration scheme and in accordance with the University of New Mexico Hospital (UNMH) Nursing Department Titration Guideline. Angiotensin II treatment will be capped at 72 hours, at which point (if a second vasopressor is still needed) the patient will be started on an alternative agent.
Angiotensin II: Angiotensin II (Giapreza) is a pharmacologic version of a naturally occurring peptide hormone of the same name which is a component of the renin-angiotensin-aldosterone system (RAAS). Angiotensin II (Giapreza) was FDA-approved in 2017 as a vasoconstrictive agent in the treatment of vasodilatory shock.
|
Standard of Care (SOC)
n=20 participants at risk
Vasopressor therapy be titrated by the clinical team per usual SOC and UNMH Nursing Department Titration Guideline. using other available vasopressor agents (e.g., higher-dose norepinephrine, vasopressin, epinephrine, phenylephrine, and/or dopamine). To provide a comparator arm, patients in the SOC will have renin and DPP3 levels obtained at equivalent timepoints.
|
|---|---|---|
|
Nervous system disorders
subarachnoid hemorrhage
|
0.00%
0/20 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
5.0%
1/20 • Number of events 1 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
|
Cardiac disorders
cardiac arrest
|
5.0%
1/20 • Number of events 2 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
0.00%
0/20 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
|
Vascular disorders
digital ischemia
|
0.00%
0/20 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
5.0%
1/20 • Number of events 1 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
|
General disorders
transfusion reaction with hypotension
|
0.00%
0/20 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
5.0%
1/20 • Number of events 1 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
|
General disorders
worsening septic shock
|
5.0%
1/20 • Number of events 1 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
0.00%
0/20 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
Other adverse events
| Measure |
Angiotensin II
n=20 participants at risk
For patients randomized to the intervention group, once the dose of background norepinephrine reaches ≥0.10 mcg/kg/min for ≥30 minutes, angiotensin II will be started at a dose of 20 ng/kg/min (recommended starting dose in package insert).Thereafter, angiotensin II and norepinephrine will both be titrated to mean arterial pressure (MAP) goal of \>/= 65 mmHg according to the protocol titration scheme and in accordance with the University of New Mexico Hospital (UNMH) Nursing Department Titration Guideline. Angiotensin II treatment will be capped at 72 hours, at which point (if a second vasopressor is still needed) the patient will be started on an alternative agent.
Angiotensin II: Angiotensin II (Giapreza) is a pharmacologic version of a naturally occurring peptide hormone of the same name which is a component of the renin-angiotensin-aldosterone system (RAAS). Angiotensin II (Giapreza) was FDA-approved in 2017 as a vasoconstrictive agent in the treatment of vasodilatory shock.
|
Standard of Care (SOC)
n=20 participants at risk
Vasopressor therapy be titrated by the clinical team per usual SOC and UNMH Nursing Department Titration Guideline. using other available vasopressor agents (e.g., higher-dose norepinephrine, vasopressin, epinephrine, phenylephrine, and/or dopamine). To provide a comparator arm, patients in the SOC will have renin and DPP3 levels obtained at equivalent timepoints.
|
|---|---|---|
|
Vascular disorders
deep vein thrombosis
|
5.0%
1/20 • Number of events 1 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
10.0%
2/20 • Number of events 2 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary embolism
|
0.00%
0/20 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
5.0%
1/20 • Number of events 1 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
|
Cardiac disorders
atrial fibrillation
|
5.0%
1/20 • Number of events 1 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
25.0%
5/20 • Number of events 5 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
|
Cardiac disorders
tachycardia
|
60.0%
12/20 • Number of events 12 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
70.0%
14/20 • Number of events 14 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
|
Endocrine disorders
hyperglycemia
|
10.0%
2/20 • Number of events 2 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
35.0%
7/20 • Number of events 7 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
|
Blood and lymphatic system disorders
thrombocytopenia
|
65.0%
13/20 • Number of events 13 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
45.0%
9/20 • Number of events 9 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
|
General disorders
lactic acidosis
|
0.00%
0/20 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
25.0%
5/20 • Number of events 5 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
|
Infections and infestations
infection
|
25.0%
5/20 • Number of events 5 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
45.0%
9/20 • Number of events 9 • 28 days
Evaluation for AEs was daily during initial 4 days of study and then weekly thereafter.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place