Early Angiotensin II in the Emergency Department (ANGIO-ED)

ANGIOtensin II for Septic Shock in the Emergency Department: ANGIO-ED Study

This pilot study will enroll 20 patients with septic shock and require emergent vasopressor support in the emergency department (ED). The primary objective of the study is to determine the feasibility of early peripheral administration of angiotensin II for treatment of septic shock in the ED

Study Overview

• Status: Recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Angiotensin II Infusion

Detailed Description

Following informed consent, patients will receive intravenous angiotensin II (AT-II) infusion for blood pressure support. The patient will remain on the AT-II infusion for 60 minutes prior to determining patient response which will be determined by recording the concurrent dose of norepinephrine and MAP every 10 minutes from initiation. If a positive response (e.g., norepinephrine dose reduction) is witnessed, the AT-II infusion will be titrated off after a maximum of 6 hours or when infusion is completed, whichever occurs first.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Brett Faine, PharmD; Phone Number: +1 319 356 2577; Email: brett-faine@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals and Clinics
      • Contact: Brett Faine; Phone Number: 3193108067; Email: brett-faine@uiowa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age ≥18; and
2. Requiring norepinephrine at a dose of 0.05-0.25 mcg/kg/min mcg/kg/minute despite adequate fluid resuscitation; and
3. Receiving intravenous antibiotics or clinician's intention to administer antibiotics at the time of enrollment; and
4. Can provide written informed consent (or legally authorized representative).

Exclusion Criteria

1. Acute coronary syndrome;
2. Cardiogenic shock;
3. Patients with a history of mesenteric ischemia;
4. Patients with a history of having an aortic dissection or abdominal aortic aneurysm;
5. Patients with an expected lifespan of <12 hours;
6. Patients with hemorrhagic shock (e.g., actively receiving transfusion of packed red blood cells);
7. Active administration of two vasoactive agents before enrollment; and
8. Pre-existing thromboembolic disease or inability to tolerate pharmacologic VTE prophylaxis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Angiotensin II Infusion	Drug: Angiotensin II Infusion; Angiotensin II continuous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of completing all clinical trial activities	Percentage of patients who provide informed consent and receive angiotensin II infusion in the emergency department	From enrollment to the end of treatment up to 6 hours after the angiotensin II infusion is initiated

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean arterial pressure response	Change in mean arterial pressure	60 minutes after the intiation of angiotensin II infusion
Mean norepinephrine dose (during angiotensin II infusion)	Change in norepinephrine dose (mcg/kg/minute) after the initiation of angiotensin II infusion	60 minutes after the intiation of angiotensin II infusion
Mean norepinephrine dose (post angiotensin II infusion)	Mean norepinephrine dose (mcg/kg/minute) after the completion of the angiotensin II infusion	60 minutes after the completion of the angiotensin II infusion

Collaborators and Investigators

• Sponsor: Brett A Faine

Publications and helpful links

General Publications

• Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hastbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Deane AM; ATHOS-3 Investigators. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Aug 3;377(5):419-430. doi: 10.1056/NEJMoa1704154. Epub 2017 May 21.
• Chawla LS, Busse L, Brasha-Mitchell E, Davison D, Honiq J, Alotaibi Z, Seneff MG. Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Crit Care. 2014 Oct 6;18(5):534. doi: 10.1186/s13054-014-0534-9.
• Wieruszewski PM, Bellomo R, Busse LW, Ham KR, Zarbock A, Khanna AK, Deane AM, Ostermann M, Wunderink RG, Boldt DW, Kroll S, Greenfeld CR, Hodges T, Chow JH; Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) Investigators. Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial. Crit Care. 2023 May 5;27(1):175. doi: 10.1186/s13054-023-04446-1.
• Avni T, Lador A, Lev S, Leibovici L, Paul M, Grossman A. Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-Analysis. PLoS One. 2015 Aug 3;10(8):e0129305. doi: 10.1371/journal.pone.0129305. eCollection 2015.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: November 14, 2024
• First Posted (Actual): November 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Angiotensin II
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Shock, Septic; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Serine Proteinase Inhibitors; Vasoconstrictor Agents; Giapreza; Angiotensin II; Angiotensinogen
• Other Study ID Numbers: 202406277

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in the manuscript, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Immediately following publication. No end date.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No