Clinical trial NCT06122987: Hemodynamic Response to Angiotensin-II When Used as the Second Vasopressor Agent for Septic Shock
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Septic Shock
Shock
Sepsis
Systemic Inflammatory Response Syndrome
Keywords: Sepsis
Angiotensin II
Hydrocortisone
Lead sponsor: Kingman Regional Medical Center
Sponsor class: OTHER
Collaborators: name: La Jolla Pharmaceutical Company
First posted: 2023-11-08
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 1 hour
Secondary outcomes:
measure: The incidence of hemodynamic response at 3 hours after initiation of angiotensin-II
timeFrame: 3 hours
measure: The incidence of hemodynamic response at 6 hours after initiation of angiotensin-II
timeFrame: 6 hours
measure: 28-day mortality
timeFrame: 28 days
measure: ICU length of stay
timeFrame: 1 year
measure: Need for renal replacement therapy
timeFrame: 1 year
measure: Vasoactive medication duration overall
timeFrame: 1 year
measure: Incidence of adverse reactions
timeFrame: 1 year
Other outcomes:
Locations:
city: Kingman
country: United States
facility: Kingman Regional Medical Center
state: Arizona
Study officials:
affiliation: Kingman Regional Medical Center
name: Tyson Dietrich, PharmD
role: PRINCIPAL_INVESTIGATOR
References: