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Renin and Renal Biomarker Response to Angiotensin II

Primary Purpose

Septic Shock, Acute Kidney Injury

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Standard of Care

Angiotensin II

About this trial

This is an interventional treatment trial for Septic Shock focused on measuring Renin, Angiotensin II, vasopressor, sepsis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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 AKI

Exclusion Criteria:

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 MAP = 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:
3 or more vasopressors required to sustain MAP
Sustained norepinephrine equivalents > 0.5 mcg/kg/min
COVID-19 positive, or high suspicion of COVID-19

Sites / Locations

University of Kentucky HealthCare Chandler Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard of Care Cohort

Angiotensin II Cohort

Arm Description

Patients in this group will receive standard of care treatment.

Patients in this group will receive angiotensin II.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in Renal Biomarkers

Cystatin C, NGAL will be measured from blood collected at baseline, 24 hours, and at shock resolution.

Time to discontinuation of catecholamines

Time from enrollment to discontinuation of catecholamines

ICU Length of Stay

Number of days in the intensive care unit (ICU).

In-hospital mortality

Assessment of all-cause mortality within hospital admission

Renal replacement therapy-free days

Days free of renal replacement therapy from enrollment up to day 28

Safety outcomes

Incidence of venous thromboembolism, arrhythmia, extremity hypoperfusion, delirium, new ischemic event, new infection

Full Information

NCT ID

NCT04558359

First Posted

September 7, 2020

Last Updated

August 8, 2023

Sponsor

Alexander Flannery

1. Study Identification

Unique Protocol Identification Number

NCT04558359

Brief Title

Renin and Renal Biomarker Response to Angiotensin II

Official Title

Renin and Renal Biomarker Response to Angiotensin II Versus Controls in Septic Shock: An Open-Label Study

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

October 19, 2020 (Actual)

Primary Completion Date

July 24, 2023 (Actual)

Study Completion Date

July 30, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Alexander Flannery

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Septic Shock, Acute Kidney Injury

Keywords

Renin, Angiotensin II, vasopressor, sepsis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Standard of Care Cohort

Arm Type

Active Comparator

Arm Description

Patients in this group will receive standard of care treatment.

Arm Title

Angiotensin II Cohort

Arm Type

Experimental

Arm Description

Patients in this group will receive angiotensin II.

Intervention Type

Other

Intervention Name(s)

Standard of Care

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Angiotensin II

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in Plasma Renin Levels

Description

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.

Time Frame

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

Secondary Outcome Measure Information:

Title

Change in Renal Biomarkers

Description

Cystatin C, NGAL will be measured from blood collected at baseline, 24 hours, and at shock resolution.

Time Frame

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

Title

Time to discontinuation of catecholamines

Description

Time from enrollment to discontinuation of catecholamines

Time Frame

Until shock resolution, up to 14 days

Title

ICU Length of Stay

Description

Number of days in the intensive care unit (ICU).

Time Frame

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

Title

In-hospital mortality

Description

Assessment of all-cause mortality within hospital admission

Time Frame

Up to 3 months following enrollment

Title

Renal replacement therapy-free days

Description

Days free of renal replacement therapy from enrollment up to day 28

Time Frame

Within 28 days of enrollment

Title

Safety outcomes

Description

Incidence of venous thromboembolism, arrhythmia, extremity hypoperfusion, delirium, new ischemic event, new infection

Time Frame

Up to 72 hours following shock resolution, no longer than 17 days from enrollment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 AKI Exclusion Criteria: 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 MAP = 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: 3 or more vasopressors required to sustain MAP Sustained norepinephrine equivalents > 0.5 mcg/kg/min COVID-19 positive, or high suspicion of COVID-19

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alexander H Flannery, Pharm.D.

Organizational Affiliation

University of Kentucky

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Kentucky HealthCare Chandler Medical Center

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40536

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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