Clinical trial NCT06746753: Dysfunctional Renin-Angiotensin System in Septic Shock
Official title: Dysfunctional Renin-Angiotensin System in Septic Shock
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Septic Shock
Keywords: sepsis
kidney disease
intensive care
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2024-12-24
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean Renin Level - Hour 24
timeFrame: Hour 24
Secondary outcomes:
measure: Norepinephrine Equivalent Dose Requirement (NEE)
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: Number of Days Without Renal Replacement Therapy
timeFrame: Day 28
measure: Number of Days of Vasopressor Use
timeFrame: Day 28
measure: Number of Days Without Mechanical Ventilation
timeFrame: Day 28
measure: Number of Hours Vasopressor Free
timeFrame: Hour 72
measure: Number of Hours Alive
timeFrame: Hour 72
measure: Number of Days Alive
timeFrame: Day 28
measure: Mean Renin Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 48
measure: Sequential Organ Failure Assessment (SOFA) Score
timeFrame: Baseline, Hour 24, Hour 48
measure: APACHE-II Score
timeFrame: Baseline, Hour 24, Hour 48
measure: Lactate Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 48
measure: Kidney Disease Improving Global Outcomes (KDIGO) Stage
timeFrame: Baseline, Hour 24, Hour 48
measure: Creatinine Level
timeFrame: Baseline, Hour 24, Hour 48
measure: BUN Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Bicarbonate Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Number of Participants with Acute Respiratory Distress Syndrome (ARDS)
timeFrame: Baseline, Hour 24, Hour 48
measure: SpO2/FiO2 Ratio Level
timeFrame: Baseline, Hour 24, Hour 48
measure: PaO2/FiO2 Ratio Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Serum Aspartate Aminotransferases Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Alanine Aminotransferases Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Alkaline Phosphatase Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Bilirubin Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Albumin Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Troponin I Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Troponin T Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Neutrophil Gelatinase-Associated Lipocalin Serum Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Neutrophil Gelatinase-Associated Lipocalin Urine Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Kidney Injury Molecule-I Urine Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Kidney Injury Molecule-I Blood Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Soluble Receptor for Advanced Glycation End Product Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Angiopoietin-2 Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Syndecan-1 Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Protein C Level
timeFrame: Baseline, Hour 24, Hour 48
measure: Neuron-Specific Enolase Level
timeFrame: Baseline, Hour 24, Hour 48
measure: S-100β Level
timeFrame: Baseline, Hour 24, Hour 48
measure: TNFα Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: sTNFR1 Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: IL-6 Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: sIL-6R Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: IL-8 Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: IL-1β Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: Interferon Gamma Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: IL12p70 Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: IL-17 Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: MIP1-alpha Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: MIP1-beta Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: IP-10 Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: IL-10 Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: IL-1RA Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: IL-12p40 Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: C reactive protein (CRP) Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: Procalcitonin Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: Platelet Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: Absolute Neutrophil Count Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: Absolute Granulocyte Count Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: Absolute Lymphocytes Count Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
measure: Neutrophil-Lymphocyte Ratio Level
timeFrame: Baseline, Hour 3, Hour 12, Hour 24, Hour 48
Other outcomes:
measure: Patients with New Deep Venous Thrombosis
timeFrame: Day 28
measure: Patients with New Pulmonary Embolism
timeFrame: Day 28
measure: Patients with New-Onset Atrial Fibrillation
timeFrame: Hour 72
measure: Patients with New-Onset Ventricular Arrhythmias
timeFrame: Hour 72
Locations:
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist
state: North Carolina
Study officials:
affiliation: Atrium Health Wake Forest Baptist
name: Ashish Khanna, MD
role: PRINCIPAL_INVESTIGATOR
References: