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

Sponsor

Kingman Regional Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06122987

Collaborator

La Jolla Pharmaceutical Company (Industry)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Septic Shock Shock Sepsis Systemic Inflammatory Response Syndrome	Drug: Angiotensin II and hydrocortisone sodium succinate	Phase 4

Detailed Description

Objectives:

Primary Objective:

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

Secondary Objectives:

To assess the duration of response to ang-II
To assess overall survival
To assess the amount of time spent in the ICU
To assess the need for renal replacement therapy
To assess the overall duration of vasoactive medication use
To assess toxicity and tolerability

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single Arm Drug: Angiotensin II Other Names: Giapreza	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. Other Names: Giapreza

Arm

Intervention/Treatment

Experimental: Single Arm

Drug: Angiotensin II Other Names: Giapreza

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.

Other Names:

Giapreza

Outcome Measures

Primary Outcome Measures

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 [1 hour]
Defined as a decrease in norepinephrine-equivalent dose with a MAP ≥65 mm Hg at 1 hour after initiation of angiotensin-II.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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