Septic ShockPhase 4NCT04558359
Renin and Renal Biomarker Response to Angiotensin II
A Phase 4 study testing Angiotensin II in people with Septic Shock and Acute Kidney Injury, run by Alexander Flannery at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock, Acute Kidney Injury
- What is being tested?
- Angiotensin II
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Oct 2020to 30 Jul 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kentucky HealthCare Chandler Medical Center
Lexington, Kentucky, 40536
About this study
Official title: Renin and Renal Biomarker Response to Angiotensin II Versus Controls in Septic Shock: An Open-Label Study
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
- Being tested
- Standard of Care, Angiotensin II
- Keywords
- Renin, Angiotensin II, vasopressor, sepsis
- Medical subject headings
- Shock, Septic, Acute Kidney Injury, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of CareOther
These patients will receive standard of care treatment. Plasma renin levels and biomarkers of renal function will be measured.
Angiotensin IIDrug
These patients will receive angiotensin II in addition to standard of care treatment. Plasma renin levels and biomarkers of renal function will be measured.
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care Cohort | Active comparator | Patients in this group will receive standard of care treatment. Receives: Other: Standard of Care |
| Angiotensin II Cohort | Experimental | Patients in this group will receive angiotensin II. Receives: Drug: Angiotensin II |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Cystatin C will be measured from blood collected at baseline, 24 hours, and at shock resolution.
Measured: 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
Days from enrollment to discontinuation of catecholamines
Measured: Until shock resolution, up to 14 days
ICU Length of Stay
Number of days in the intensive care unit (ICU).
Measured: From enrollment to ICU discharge, up to 28 days following enrollment
Number of Participants With In-hospital Mortality
Assessment of all-cause mortality within hospital admission
Measured: Up to 3 months following enrollment
Renal Replacement Therapy-free Days
Days free of renal replacement therapy from enrollment up to day 28
Measured: Within 28 days of enrollment
Number of Participants Experiencing Prespecified Safety Outcomes
Incidence of venous thromboembolism, arrhythmia, extremity hypoperfusion, delirium, new ischemic event, new infection
Measured: Up to 72 hours following shock resolution, no longer than 17 days from enrollment
Change in Plasma Neutrophil Gelatinase-associated Lipocalin (NGAL)
NGAL will be measured from blood collected at baseline, 24 hours, and at shock resolution.
Measured: Until shock resolution, up to 14 days (at baseline, 3 hours, 24 hours, and shock resolution, up to 14 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2020
- Study start19 Oct 2020
- Primary completion24 Jul 2023
- Study completion30 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexander Flannery
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Alexander Flannery, University of Kentucky
- Investigators
- Alexander H Flannery, Pharm.D., Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04558359
- Sponsor's protocol ID
- 57411
- Status last verified
- Aug 2024
- First submitted
- 7 Sep 2020
- Last updated
- 4 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renin and Renal Biomarker Response to Angiotensin II Versus Controls in Septic Shock: An Open-Label Study
- ClinicalTrials.gov ID
- NCT04558359
- Acronym / sponsor ID
- 57411
- Conditions
- Septic Shock, Acute Kidney Injury
- Keywords
- Renin, Angiotensin II, vasopressor, sepsis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Alexander FlanneryUniversity, hospital or other
- Study start
- 19 Oct 2020 (actual)
- Primary completion
- 24 Jul 2023 (actual)
- Study completion
- 30 Jul 2023 (actual)
- First posted
- 22 Sep 2020 (actual)
- Results
- Posted 4 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care Cohort | Active comparator | Other: Standard of CarePatients in this group will receive standard of care treatment. |
| Angiotensin II Cohort | Experimental | Drug: Angiotensin IIPatients in this group will receive angiotensin II. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (14 listed)
- Prisoner
- Pregnancy
- Acute occlusive coronary syndrome requiring intervention or acute myocardial infarction of any degree
- Purely cardiogenic shock (no distributive component)
- Mesenteric ischemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard of CareThese patients will receive standard of care treatment. Plasma renin levels and biomarkers of renal function will be measured. | Other | Standard of Care Cohort |
| Angiotensin IIThese patients will receive angiotensin II in addition to standard of care treatment. Plasma renin levels and biomarkers of renal function will be measured. | Drug | Angiotensin II Cohort |
Primary outcome
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.
7 secondary outcomes
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)
Days to Discontinuation of Catecholamines
Time frame: Until shock resolution, up to 14 days
ICU Length of Stay
Time frame: From enrollment to ICU discharge, up to 28 days following enrollment
Number of Participants With In-hospital Mortality
Time frame: Up to 3 months following enrollment
Renal Replacement Therapy-free Days
Time frame: Within 28 days of enrollment
Number of Participants Experiencing Prespecified Safety Outcomes
Time frame: Up to 72 hours following shock resolution, no longer than 17 days from enrollment
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexander H Flannery, Pharm.D. principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Angiotensin II in people with Septic Shock and Acute Kidney Injury, run by Alexander Flannery at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2024.