Clinical trial NCT06693726: Early Angiotensin II in the Emergency Department
Official title: ANGIOtensin II for Septic Shock in the Emergency Department: ANGIO-ED Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Septic Shock
Keywords: Angiotensin II
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2024-11-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This pilot study will enroll 20 patients with septic shock and require emergent vasopressor support in the emergency department (ED). The primary objective of the study is to determine the feasibility of early peripheral administration of angiotensin II for treatment of septic shock in the ED

Detailed description: Following informed consent, patients will receive intravenous angiotensin II (AT-II) infusion for blood pressure support. The patient will remain on the AT-II infusion for 60 minutes prior to determining patient response which will be determined by recording the concurrent dose of norepinephrine and MAP every 10 minutes from initiation. If a positive response (e.g., norepinephrine dose reduction) is witnessed, the AT-II infusion will be titrated off after a maximum of 6 hours or when infusion is completed, whichever occurs first.

Eligibility criteria: Inclusion Criteria

1. Age ≥18; and
2. Requiring norepinephrine at a dose of 0.05-0.25 mcg/kg/min mcg/kg/minute despite adequate fluid resuscitation; and
3. Receiving intravenous antibiotics or clinician's intention to administer antibiotics at the time of enrollment; and
4. Can provide written informed consent (or legally authorized representative).

Exclusion Criteria

1. Acute coronary syndrome;
2. Cardiogenic shock;
3. Patients with a history of mesenteric ischemia;
4. Patients with a history of having an aortic dissection or abdominal aortic aneurysm;
5. Patients with an expected lifespan of \<12 hours;
6. Patients with hemorrhagic shock (e.g., actively receiving transfusion of packed red blood cells);
7. Active administration of two vasoactive agents before enrollment; and
8. Pre-existing thromboembolic disease or inability to tolerate pharmacologic VTE prophylaxis.

Primary outcomes:
measure: Feasibility of completing all clinical trial activities
timeFrame: From enrollment to the end of treatment up to 6 hours after the angiotensin II infusion is initiated
Secondary outcomes:
measure: Mean arterial pressure response
timeFrame: 60 minutes after the intiation of angiotensin II infusion
measure: Mean norepinephrine dose (during angiotensin II infusion)
timeFrame: 60 minutes after the intiation of angiotensin II infusion
measure: Mean norepinephrine dose (post angiotensin II infusion)
timeFrame: 60 minutes after the completion of the angiotensin II infusion
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
Study officials:
References:
citation: Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hastbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Deane AM; ATHOS-3 Investigators. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Aug 3;377(5):419-430. doi: 10.1056/NEJMoa1704154. Epub 2017 May 21.
citation: Chawla LS, Busse L, Brasha-Mitchell E, Davison D, Honiq J, Alotaibi Z, Seneff MG. Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Crit Care. 2014 Oct 6;18(5):534. doi: 10.1186/s13054-014-0534-9.
citation: Wieruszewski PM, Bellomo R, Busse LW, Ham KR, Zarbock A, Khanna AK, Deane AM, Ostermann M, Wunderink RG, Boldt DW, Kroll S, Greenfeld CR, Hodges T, Chow JH; Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) Investigators. Initiating angiotensin II at lower vasopressor doses in vasodilatory shock: an exploratory post-hoc analysis of the ATHOS-3 clinical trial. Crit Care. 2023 May 5;27(1):175. doi: 10.1186/s13054-023-04446-1.
citation: Avni T, Lador A, Lev S, Leibovici L, Paul M, Grossman A. Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-Analysis. PLoS One. 2015 Aug 3;10(8):e0129305. doi: 10.1371/journal.pone.0129305. eCollection 2015.