Renin and Renal Biomarker Response to Angiotensin II

NCT04558359 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 57411
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Septic shock continues to exert a large economic burden around the world. Several developments have occurred that lead to the current study. First, angiotensin II is the newest FDA approved vasopressor agent indicated for use in vasodilatory shock. Several subgroups from the approval trial have indicated that angiotensin II may confer a survival benefit in certain conditions, including those patients requiring continuous renal replacement therapy, those with altered angiotensin I: angiotensin II ratios, and most recently, those with elevated renin levels (which may serve as a surrogate for dysfunctional angiotensin 1: angiotensin II ratios). This open-label, sequential period pilot study will evaluate angiotensin II and biomarker response (renin) in the treatment of septic shock.

Conditions

Septic Shock; Acute Kidney Injury

Keywords

Renin; Angiotensin II; vasopressor; sepsis

Outcome Measures

Primary Outcomes (1)

• Change in Plasma Renin Levels

  Plasma renin levels will be measured from blood collected at baseline, 24 hours, and at shock resolution. Additionally, a 3-hour measurement will be included in the angiotensin II arm.

  Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)

Secondary Outcomes (7)

• Change in Plasma Cystatin C

  Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)

• Days to Discontinuation of Catecholamines

  Until shock resolution, up to 14 days

• ICU Length of Stay

  From enrollment to ICU discharge, up to 28 days following enrollment

• Number of Participants With In-hospital Mortality

  Up to 3 months following enrollment

• Renal Replacement Therapy-free Days

  Within 28 days of enrollment

Study Arms (2)

Standard of Care Cohort

ACTIVE COMPARATOR

Patients in this group will receive standard of care treatment.

Other: Standard of Care

Angiotensin II Cohort

EXPERIMENTAL

Patients in this group will receive angiotensin II.

Drug: Angiotensin II

Interventions

Standard of Care OTHER

These patients will receive standard of care treatment. Plasma renin levels and biomarkers of renal function will be measured.

Standard of Care Cohort

Angiotensin II DRUG

These patients will receive angiotensin II in addition to standard of care treatment. Plasma renin levels and biomarkers of renal function will be measured.

Angiotensin II Cohort

Eligibility Criteria

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

You may qualify if:

• Medical ICU admission
• Septic shock
• Norepinephrine requirement = 0.15 mcg/kg/min for = 30 minutes (if cirrhosis, norepinephrine requirement = 0.1 mcg/kg/min for = 30 minutes)
• Kidney Disease Improving Global Outcomes stage 1 or greater Acute Kidney Injury

You may not qualify if:

• Prisoner
• Pregnancy
• Acute occlusive coronary syndrome requiring intervention or acute myocardial infarction of any degree
• Purely cardiogenic shock (no distributive component)
• Mesenteric ischemia
• Acute ischemic stroke
• Hemorrhagic shock
• Active treatment of hepatorenal syndrome targeting a Mean Arterial Pressure = 65 mm Hg
• Planned withdrawal of care within next 24 hours or no escalation of care
• Patient enrolled in an interventional study
• High likelihood of medical futility in using this drug:
• or more vasopressors required to sustain MAP
• Sustained norepinephrine equivalents \> 0.5 mcg/kg/min
• COVID-19 positive, or high suspicion of COVID-19

Sponsors & Collaborators

• Alexander Flannery: lead

Study Sites (1)

University of Kentucky HealthCare Chandler Medical Center

Lexington, Kentucky, 40536, United States

Location

MeSH Terms

Conditions

Shock, Septic; Acute Kidney Injury; Sepsis

Interventions

Standard of Care; Angiotensin II

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; 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

Results Point of Contact

• Title: Alexander Flannery, PharmD, PhD
• Organization: University of Kentucky

alexander.flannery@gmail.com

859-562-2766

Study Officials

• Alexander H Flannery, Pharm.D.

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 7, 2020
• First Posted: September 22, 2020
• Study Start: October 19, 2020
• Primary Completion: July 24, 2023
• Study Completion: July 30, 2023
• Last Updated: September 4, 2024
• Results First Posted: September 4, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)