Mechanistic Assessment of Norepinephrine Therapy vs. Angiotensin-II in Septic Shock

NCT06746753 | Not Yet Recruiting Phase 4 FDA Drug

• 2 other identifiers: IRB00115287R01HL177834
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 2

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.

Conditions

Septic Shock

Keywords

sepsis; kidney disease; intensive care

Outcome Measures

Primary Outcomes (1)

• Mean Renin Level - Hour 24

  Mean plasma renin level (PRA) as a measure of renin-angiotensin-aldosterone system restoration. Normal levels of active renin \<1.1 pM (40 pg/mL). A level higher than normal can indicate level of shock.

  Hour 24

Secondary Outcomes (69)

• Norepinephrine Equivalent Dose Requirement (NEE)

  Baseline, Hour 3, Hour 12, Hour 24, Hour 48, Hour 72

• Number of Days Without Renal Replacement Therapy

  Day 28

• Number of Days of Vasopressor Use

  Day 28

• Number of Days Without Mechanical Ventilation

  Day 28

• Number of Hours Vasopressor Free

  Hour 72

Other Outcomes (4)

• Patients with New Deep Venous Thrombosis

  Day 7, Day 28

• Patients with New Pulmonary Embolism

  Day 7, Day 28

• Patients with New-Onset Atrial Fibrillation

  Hour 72, day 28

Study Arms (2)

Angiotensin II

EXPERIMENTAL

Continuous infusion of Angiotensin II for up to 48 hours

Drug: Angiotensin II

Norepinephrine

ACTIVE COMPARATOR

Continuous infusion of Norepinephrine for up to 48 hours

Drug: Norepinephrine

Interventions

Angiotensin II DRUG

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

Angiotensin II

Norepinephrine DRUG

randomized to receive Norepinephrine continuous infusion for up to 48 hours

Norepinephrine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- The presence of septic shock, defined by sepsis-3 criteria: 1-adult patients (18 years or older) with septic shock, defined by SEPSIS-3 criteria: a) suspected or known infection, b) hypotension requiring vasopressors, and c) lactate \>2mmol/L 2-receiving either norepinephrine or phenylephrine with or without additional vasopressor support 3- total norepinephrine equivalent dose (NED) ≥0.1 mcg/kg/min and ≤0.5 mcg/kg/min, to maintain a MAP of at least 65 mmHg, is required for randomization 4-ability to consent and randomize within 24 hrs of first reaching NED threshold and within 48 hrs of hospital arrival

You may not qualify if:

• 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, including withdraw of vasopressor support
• transfer from outside ICU
• history of liver cirrhosis with Child-Pugh score ≥6

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

Massachusetts General Hospital-Harvard

Boston, Massachusetts, 02114, United States

Location

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Shock, Septic; Sepsis; Kidney Diseases

Interventions

Angiotensin II; Norepinephrine

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Angiotensins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Autacoids; Inflammation Mediators; Biological Factors; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Ashish Khanna, MD

  Atrium Health Wake Forest Baptist

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ashish Khanna, MD

CONTACT

513-658-5866; ashish.khanna@wfusm.edu

Lynnette Harris, RN

CONTACT

336-716-8791; lynnette.harris@advocatehealth.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2024
• First Posted: December 24, 2024
• Study Start: May 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)