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Completed

NCT Number: NCT04558359

Renin and Renal Biomarker Response to Angiotensin II

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University of Kentucky HealthCare Chandler Medical Center

Lexington, Kentucky, 40536, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 Acute Kidney Injury

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 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:
  • 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

Treatment and study plan

Standard of care

Other

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

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.

Primary outcomes

  1. Change in Plasma Renin Levels

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

    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 outcomes

  1. Change in Plasma Cystatin C

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

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

  2. Days to Discontinuation of Catecholamines

    Time frame: Until shock resolution, up to 14 days

    Days from enrollment to discontinuation of catecholamines

  3. ICU Length of Stay

    Time frame: From enrollment to ICU discharge, up to 28 days following enrollment

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

  4. Number of Participants With In-hospital Mortality

    Time frame: Up to 3 months following enrollment

    Assessment of all-cause mortality within hospital admission

  5. Renal Replacement Therapy-free Days

    Time frame: Within 28 days of enrollment

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

  6. Number of Participants Experiencing Prespecified Safety Outcomes

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

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

  7. Change in Plasma Neutrophil Gelatinase-associated Lipocalin (NGAL)

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

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

Sponsors and collaborators

Lead sponsor

Alexander Flannery

Other

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2023
Study completion
2023
First posted
Sep 22, 2020
Registry last updated
Sep 4, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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