Dysfunctional Renin-Angiotensin System in Septic Shock

NCT ID: NCT06746753

Last Updated: 2026-01-27

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-03-31
• Study Completion Date: 2028-08-31

Brief Summary

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.

Detailed 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.

Conditions

Septic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Angiotensin II

Continuous infusion of Angiotensin II for up to 48 hours

Group Type: EXPERIMENTAL

Angiotensin II

Intervention Type: DRUG

randomized to receive Angiotensin II continuous infusion for up to 48 hours

Norepinephrine

Continuous infusion of Norepinephrine for up to 48 hours

Group Type: ACTIVE_COMPARATOR

Norepinephrine

Intervention Type: DRUG

randomized to receive Norepinephrine continuous infusion for up to 48 hours

Interventions

Angiotensin II

randomized to receive Angiotensin II continuous infusion for up to 48 hours

Intervention Type: DRUG

Norepinephrine

randomized to receive Norepinephrine continuous infusion for up to 48 hours

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ashish Khanna, MD

Role: PRINCIPAL_INVESTIGATOR

Atrium Health Wake Forest Baptist

Locations

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, United States

Countries

United States

Central Contacts

Ashish Khanna, MD

Role: CONTACT

akhanna@wakehealth.edu

513-658-5866

Lynnette Harris, RN

Role: CONTACT

lcharris@wakehealth.edu

336-716-8791

Other Identifiers

11773

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00115287

Identifier Type: -

Identifier Source: org_study_id