Angiotensin II for Post Cardiac Surgery Vasoplegia (ANGII_V) (ANGII_V)

The goal of this study is to conduct a prospective trial implementing a modified version of the Emory Protocol for administering ANG II to patients with post cardiac bypass vasoplegia. The main questions we aim to answer are: 1.) does administration of improve mortality, 2.) does the administration of Ang II using the modified protocol shorten the time needed to reach optimal MAP, 3.) does the administration of Ang II using the modified protocol shorten length of stay in the ICU and hospital? Researchers will compare outcomes from the interventional group to historical controls who did not receive Ang II using the modified protocol.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiopulmonary Bypass; Vasoplegia; Vasoplegic Shock
• Intervention / Treatment: Drug: Angiotensin II (Giapreza®)

Detailed Description

Giapreza is a synthetic human Ang II treatment which acts as a RAAS pathway regulator to rais MAP in adults. This will be a single center study comparing patients treated with a modified Emory protocol to historical controls who have not received Ang II. We will observe the effects of using a modified version of the Emory protocol, which includes lowering the dosages needed for norepinephrine and vasopressin. Additionally, clinicians will administer Ang II prior to starting methylene blue, a drug that poses more risk to patients than Ang II. Using this modified version of this protocol, patients who have post cardiopulmonary bypass vasoplegia who are already on vasopressin 0.04 units/min, norepinephrine 0.1 mcg/kg/min will have Ang II initiated at 10 to 20 ng/kg/min and titrated by 10 ng/kg/min every 5 minutes to a maximum dose of 80 ng/kg/min. If patients do not achieve their MAP goal of 65mmHg or greater within 3 hours, then they will have ANG II discontinued and will receive a dose of methylene blue at 2 mg/kg. If the patients do not achieve their MAP goal with methylene blue then they will receive a cyanokit.

• Study Type: Interventional
• Enrollment (Estimated): 329
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:

  1. Provision of signed and dated informed consent form
  2. Stated willingness to comply with all study procedures and availability for the duration of the study
  3. Male or female, aged 18 or over
  4. Exhibiting vasoplegia or vasoplegic shock following surgeries involving cardiopulmonary bypass
  5. MAP below results below 65mmHg

Exclusion Criteria:

• An individual who meets any of the following criteria will be excluded from participation in this study:

  1. Current use of angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs)
  2. Presence of treatment with high-dose glucocorticoids
  3. Pregnancy or lactation
  4. Known allergic reactions to components of the Giapreza, <specify components/allergens>
  5. Febrile illness within <specify time frame>
  6. Treatment with another investigational drug or other intervention within <specify time frame>
  7. Current smoker or tobacco use within <specify timeframe>
  8. Currently receiving VA ECMO for cardiogenic shock
  9. Experiencing uncontrolled hemorrhage
  10. Presenting with burns over 20% or more of body, acute coronary syndrome, bronchial spasms, liver failure, mesenteric ischemia, abdominal aortic aneurysm, or an absolute neutrophil count less than 1000 cubic millimeters

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ang II Administration using a modified Emory protocol; Using this modified version of this protocol, patients who have post cardiopulmonary bypass vasoplegia who are already on vasopressin 0.04 units/min, norepinephrine 0.1 mcg/kg/min will have Ang II initiated at 10 to 20 ng/kg/min and titrated by 10 ng/kg/min every 5 minutes to a maximum dose of 80 ng/kg/min. Case report forms (CRF) tracking MAP and dosage of drugs will be completed for each patient for up to 48 hours.	Drug: Angiotensin II (Giapreza®); Patients who have post cardiopulmonary bypass vasoplegia who are already on vasopressin 0.04 units/min, norepinephrine 0.1 mcg/kg/min will have Ang II initiated at 10 to 20 ng/kg/min and titrated by 10 ng/kg/min every 5 minutes to a maximum dose of 80 ng/kg/min.
No Intervention: Evaluating Effectiveness of modified Emory Protocol on outcomes from vasoplegia after bypass; Historical controls will be extracted from EMR and selected based on 1:1 matching with patients in experimental arm. Matching will be based on a number of factors. Descriptive and comparative analyses will be conducted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	in-hospital or post-hospital mortality within 1 year	365 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Arterial Pressure	Changes in Mean Arterial Pressure	Hours 3, 6, 9, 12, 24 and 48,
Length of Stay	ICU	1 year
Length of Stay	In Hospital, post ICU	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Re-admission	Re-admission to hospital for related event	1 year

Collaborators and Investigators

• Sponsor: Methodist Healthcare System of San Antonio

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.
• Busse LW, Barker N, Petersen C. Vasoplegic syndrome following cardiothoracic surgery-review of pathophysiology and update of treatment options. Crit Care. 2020 Feb 4;24(1):36. doi: 10.1186/s13054-020-2743-8.
• Ten Lohuis CC, Burke SC, Jannuzzo CJ, Barker NA, Chen EP, Busse LW. Protocol Compliance Guiding Angiotensin II Use in Post Cardiovascular Surgery Vasoplegia. Crit Care Explor. 2022 May 13;4(5):e0687. doi: 10.1097/CCE.0000000000000687. eCollection 2022 May.

Helpful Links

• Giapreza drug information and package insert
• Giapreza drug information

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): August 1, 2030

Study Registration Dates

• First Submitted: June 22, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 26, 2026

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vasoplegia; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Biological Factors; Autacoids; Inflammation Mediators; Angiotensins; Giapreza; Angiotensin II
• Other Study ID Numbers: ANGIIV01

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 any article, after deidentification (text,tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 9 months after and ending 36 months following any article publication.
• IPD Sharing Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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