Hemodynamic Response to Angiotensin-II When Used as the Second Vasopressor Agent for Septic Shock

Sepsis Clinical Trial

Official title:

An Open-label, Single-arm, Single-center Study Evaluating the Hemodynamic Response to Angiotensin-II When Used as the Second Vasopressor Agent for Septic Shock

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06122987
• Other study ID #: KRMC 0284
• Status: Recruiting
• Phase: Phase 4
• Start date: December 4, 2023
• Est. completion date: January 2025

Study information

• Verified date: May 2024
• Source: Kingman Regional Medical Center
• Contact: Tyson Dietrich, PharmD
• Phone: 928-263-3933
• Email: TDietrich[@]azkrmc.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Norepinephrine is a catecholamine that is the first-line vasopressor for septic shock. The addition of non-catecholamine vasopressors, including vasopressin and angiotensin-II may be used in adults with septic shock that have inadequate mean arterial pressure while on norepinephrine. Uncertainty exists regarding the timing of initiation of these agents and there is a lack of data comparing their safety and efficacy.

The current literature suggests that earlier initiation of angiotensin-II will have a more significant reduction on norepinephrine-equivalent dose compared to later initiation. In addition, approximately half of patients initiated on vasopressin do not have an early hemodynamic response 6 hours after initiation. The purpose of this study is to evaluate the efficacy of angiotensin-II when used as the second vasopressor agent for septic shock.

Description:

Objectives:

Primary Objective:

1. To evaluate the efficacy of ang-II when used as the second vasopressor agent for septic shock

Secondary Objectives:

1. To assess the duration of response to ang-II

2. To assess overall survival

3. To assess the amount of time spent in the ICU

4. To assess the need for renal replacement therapy

5. To assess the overall duration of vasoactive medication use

6. To assess toxicity and tolerability

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients admitted to the ICU within 12 hours of presentation to the emergency department for septic shock requiring 15-25 mcg/min of norepinephrine. Septic shock will be defined as having a known or presumed infection with two or more criteria of systemic inflammatory response syndrome, a mean arterial pressure <65 mm Hg despite fluid resuscitation requiring vasopressor support, and a serum lactate >2 mmol/L. Criteria of systemic inflammatory response syndrome include a temperature >100.4°F or <96.8°F; heart rate >90/min; respiratory rate >20/min and a white blood cell count >12,000/mm3 or <4,000/mm3.

Exclusion Criteria:

• Age <18 years

• Pregnancy or lactation

• Known allergic reactions to angiotensin-II or hydrocortisone sodium succinate

• Requiring >25 mcg/min of norepinephrine or on any vasopressor other than norepinephrine at study enrollment

• Clinically significant bleeding precluding the use of chemical prophylaxis for venous thromboembolism

• Treatment with another investigational drug or other intervention during study timeframe

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Shock
• Shock, Septic
• Systemic Inflammatory Response Syndrome

Intervention

Drug:
• Angiotensin II and hydrocortisone sodium succinate
Intravenous infusion angiotensin II (titrated for each individual patient by effect) and hydrocortisone 50 mg intravenous bolus every 6 hours.

Locations

Country	Name	City	State
United States	Kingman Regional Medical Center	Kingman	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Kingman Regional Medical Center	La Jolla Pharmaceutical Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of hemodynamic response, defined as a decrease in norepinephrine-equivalent dose with a MAP =65 mm Hg at 1 hour after initiation of angiotensin-II	Defined as a decrease in norepinephrine-equivalent dose with a MAP =65 mm Hg at 1 hour after initiation of angiotensin-II.	1 hour
Secondary	The incidence of hemodynamic response at 3 hours after initiation of angiotensin-II	Defined as a decrease in norepinephrine-equivalent dose with a MAP =65 mm Hg at 3 hours after initiation of angiotensin-II.	3 hours
Secondary	The incidence of hemodynamic response at 6 hours after initiation of angiotensin-II	Defined as a decrease in norepinephrine-equivalent dose with a MAP =65 mm Hg at 6 hours after initiation of angiotensin-II.	6 hours
Secondary	28-day mortality	Defined as all cause mortality up to 28 days from study enrollment.	28 days
Secondary	ICU length of stay	Defined as the time spent within the ICU until discharge to a step down unit.	1 year
Secondary	Need for renal replacement therapy	Defined as patients started on either continuous renal replacement therapy (CRRT) or intermittent hemodialysis (IHD) during the study period.	1 year
Secondary	Vasoactive medication duration overall	Defined as the duration (hours) of vasoactive medication use during the study period.	1 year
Secondary	Incidence of adverse reactions	Define as an unexpected or unintended effect suspected to be caused by a medicine.	1 year