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

Phase 4

Recruiting

• Conditions: Septic Shock; Shock; Sepsis; Systemic Inflammatory Response Syndrome
• Interventions: Drug: Angiotensin II and hydrocortisone sodium succinate

• Registration Number: NCT06122987
• Lead Sponsor: Kingman Regional Medical Center

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.

Detailed 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

Study Timeline

• Study First Submitted: 2023-11-03
• Study First Submitted QC: 2023-11-03
• Study First Posted: 2023-11-08
• Study Start: 2023-12-04
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-21
• Last Update Posted: 2024-05-23
• Primary Completion: 2024-12
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Arm	Angiotensin II and hydrocortisone sodium succinate	Drug: Angiotensin II Other Names: Giapreza

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
Vasoactive medication duration overall	1 year	Defined as the duration (hours) of vasoactive medication use during the study period.
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.
Incidence of adverse reactions	1 year	Define as an unexpected or unintended effect suspected to be caused by a medicine.

Trial Locations

Locations (1)

Kingman Regional Medical Center; 🇺🇸 Kingman, Arizona, United States