Dysfunctional Renin-Angiotensin System in Septic Shock

Wake Forest University (WFU)

Status and phase: Begins enrollment this month; Phase 4

Conditions: Septic Shock

Treatments: Drug: Angiotensin II; Drug: Norepinephrine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06746753

11773 (Registry Identifier)

IRB00115287

Details and patient eligibility

About

Despite best therapy efforts, sepsis and septic shock are associated with mortality rates of up to 40%. This clinical trial will determine the benefit of exogenous Angiotensin II versus norepinephrine (conventional care) treatment in septic shock patients. This trial will determine whether there are better predictors of septic shock severity. This approach may inform more appropriate treatment regimens and improve outcomes for these patients.

Full description

This study will determine whether normalization of renin-angiotensin-aldosterone system (RAAS) signaling in sepsis occurs more rapidly with treatment with Angiotensin II compared with conventional vasopressors. Trial samples will be used to identify the best RAAS biomarker predictor of treatment response via in-depth longitudinal analysis of RAAS component and to determine the extent and mechanisms of Angiotensin II impact on innate immune function during sepsis. Successful accomplishment of our aims will provide the capability to improve endotyping of septic patients by establishing the most precise and robust measurement of renin (and RAAS dysfunction). This work will improve staging and clinical precision and will facilitate the criteria for therapeutic development of targets in septic shock.

Enrollment: 78 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• The presence of septic shock, defined by sepsis-3 criteria
• The requirement for Norepinephrine of at least 10 micrograms/minute up to 35 micrograms/minute for at least 1 hour, with or without Vasopressin, to maintain a mean arterial pressure of 65 mmHg
• Clinical suspicion or proven evidence of infection

Exclusion criteria

• Age <18 years
• Prisoners
• Pregnant women
• Patients for whom urgent surgery is anticipated
• Leukocyte count <1,000 cells/μL
• Absolute monocyte count <200 cells/μL
• Bone marrow transplant within the past 30 days
• Patients that will be withdrawing aggressive resuscitation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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78 participants in 2 patient groups

Angiotensin II

Experimental group

Description:

Continuous infusion of Angiotensin II for up to 48 hours

Treatment:

Drug: Angiotensin II

Norepinephrine

Active Comparator group

Description:

Continuous infusion of Norepinephrine for up to 48 hours

Treatment:

Drug: Norepinephrine