Comparison of Angiotensin II to Standard Dose Vasopressors on Change in Arterial Elastance

NCT07568275 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: 24-913
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A study to see whether a medication called Angiotensin II works better than the routinely used medication to raise blood pressure in people with liver disease who are experiencing a serious drop in blood pressure. The investigators want to find out if Angiotensin II can help the heart and blood vessels work together more effectively than standard treatments.

Conditions

Septic Shock; Cirrhosis; Vasodilatory Shock; Acute Kidney Injury

Outcome Measures

Primary Outcomes (2)

• Change in arterial elastance

  Change in arterial elastance will be measure by echocardiography at baseline, 6 hours and 24 hours. Dynamic arterial elastance will be calculated as the ratio between pulse pressure variation and stroke volume variation obtained from arterial line waveform.

  6 hours

• Change in arterial elastance

  Change in arterial elastance will be measure by echocardiography at baseline, 6 hours and 24 hours. Dynamic arterial elastance will be calculated as the ratio between pulse pressure variation and stroke volume variation obtained from arterial line waveform.

  24 hours

Secondary Outcomes (11)

• Change in arterial ventricular coupling

  6 hours

• Change in arterial ventricular coupling

  24 hours

• Change in norepinephrine equivalent dose

  6 hours

• Change in norepinephrine equivalent dose

  24 hours

• Change in renal perfusion index

  6 hours

Study Arms (2)

Angiotensin II

ACTIVE COMPARATOR

Angiotensin II will be continued for 24 hours and then discontinued, and SOC vasopressors resumed according to institutional practices.

Drug: Giapreza

Standard of Care

NO INTERVENTION

Fixed-dose vasopressin and standard of care vasopressors increased as per institutional guidelines according to MAP targets.

Interventions

Giapreza DRUG

2.5 mg/mL

Also known as: Angiotension II

Angiotensin II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at the time of enrollment
• Septic shock as defined by Sepsis-3 criteria (highly suspected or confirmed infection, requiring norepinephrine to maintain a MAP ≥ 65 mmHg, and serum lactate \> 2 mmol/L after adequate fluid resuscitation) within a 48 hour window prior to enrollment
• Confirmed cirrhotic patient (Radiological/Biopsy/Physician confirmed)
• Preserved cardiac function as assessed using point-of-care ultrasonography or a non-invasive hemodynamic monitoring device with either LVOT VTI \> 18 cm or stroke volume \> 50 ml Within 48 hours of onset of shock.
• Standard of care vasopressors are at a norepinephrine equivalent of 15 mcg/min

You may not qualify if:

• Declined consent.
• Pregnancy
• CKD-Stage IV/V
• ESRD on long-term hemodialysis
• On Dialysis or planned dialysis to be initiated within 24 hours of study of enrollment.
• Clinically determined to have primarily hepatorenal syndrome.
• On other vasoactive medication (phenylephrine, Terlipressin, epinephrine, dobutamine, dopamine)
• Hemorrhagic, obstructive, or hypovolemic shock is not the primary cause of shock based on clinical judgement.
• DNR
• Patients declared Brain dead.
• Anticipated death within 48 hours of enrollment
• Echocardiographic windows not available
• Acute mesenteric Ischemia
• Active gastrointestinal bleeding
• Active cardiac ischemic event defined as NSTEMi, STEMI

Sponsors & Collaborators

• The Cleveland Clinic: lead
• Innoviva Specialty Therapeutics: collaborator

Study Sites (1)

The Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Shock, Septic; Fibrosis; Acute Kidney Injury

Interventions

Giapreza; angiotensin II, Phe(4)-

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Siddharth Dugar, M.D.

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: For the angiotensin 2 arm, SOC vasopressors will be continued at fixed dose after initiation of angiotensin 2 (e.g. norepinephrine 12-15 mcg/min). * If MAP \< goal (MAP goal of 65-70 per physician discretion), angiotensin II will be initiated per the following titration schema: • Initial dose 10 ng/kg/min, titrate by 10-15 ng/kg/min every 5-15 min to target MAP goal. Max dose 80 ng/kg/min * Once Angiotensin II is at a max dose of 80 ng/kg/min and MAP \< goal, SOC vasopressor may be increased per institutional guideline. * If MAP \> goal during Angiotensin II therapy, SOC vasopressor should be weaned first until SOC vasopressor at norepinephrine of 15 mcg/min followed by angiotensin 2. Angiotensin II will be continued for 24 hours and then discontinued, and SOC vasopressors resumed according to institutional practices. For the SOC arm, patients will be continued on SOC vasopressors per institutional practices to MAP target.

Study Record Dates

• First Submitted: February 19, 2026
• First Posted: May 5, 2026
• Study Start: November 15, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Starting in January 2029.
• Access Criteria: Researchers can access the information on clinicaltrials.gov.

Locations

US (1)