Angiotensin II for Septic Shock

Overseen By Lynnette Harris, RN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Wake Forest University Health Sciences

Must be taking: Norepinephrine

Disqualifiers: Age <18, Pregnant, Surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 28

Duration: 2 days

78 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Angiotensin II for treating septic shock?

Angiotensin II has been shown to increase blood pressure in patients with septic shock, which is a critical need in this condition. It is approved by the FDA for use in adults with septic shock to help reduce the need for other blood pressure-raising drugs. ^{1 2 3 4 5}

Is Angiotensin II safe for use in humans?

Angiotensin II was approved by the FDA in 2017 for increasing blood pressure in adults with septic or other types of shock. While it is used to help with low blood pressure, more research is needed to fully understand its effects on the lungs, brain, and risk of blood clots. ^{1 3 4 5 6}

How is the drug Angiotensin II different from other treatments for septic shock?

Angiotensin II is unique because it is a vasopressor (a drug that raises blood pressure) that works by mimicking a natural hormone in the body, and it is used alongside other vasopressors to reduce the need for high doses of catecholamines, which can have serious side effects. It was approved by the FDA in 2017 specifically for increasing blood pressure in septic shock, offering a novel mechanism compared to traditional vasopressors like norepinephrine. ^{1 3 4 5 7}

Research Team

Ashish Khanna, MD

Principal Investigator

Atrium Health Wake Forest Baptist

Eligibility Criteria

This trial is for patients with septic shock, a severe infection causing dangerously low blood pressure. Participants must have confirmed sepsis and require vasopressors to maintain blood pressure. Specific inclusion or exclusion criteria are not provided but typically would involve health status and prior treatments.

Inclusion Criteria

I am currently experiencing severe sepsis with low blood pressure.

I might have or have been diagnosed with an infection.

I need Norepinephrine to keep my blood pressure at 65 mmHg.

Exclusion Criteria

I am expected to undergo urgent surgery soon.

Prisoners

Leukocyte count <1,000 cells/μL

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive continuous infusion of Angiotensin II or Norepinephrine for up to 48 hours

2 days

Continuous monitoring during treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Regular assessments at Day 28

Treatment Details

Interventions

• Angiotensin II
• Norepinephrine

Trial Overview The study is testing the effectiveness of Angiotensin II compared to norepinephrine in treating septic shock. It aims to find out if Angiotensin II can better predict the severity of septic shock and improve patient outcomes than the conventional treatment.

Participant Groups

Group I: Angiotensin II Experimental Treatment 1 Intervention

Continuous infusion of Angiotensin II for up to 48 hours

Group II: Norepinephrine Active Control 1 Intervention

Continuous infusion of Norepinephrine for up to 48 hours

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Findings from Research

In a study of 147 adult patients in the ICU requiring multiple vasopressors for septic shock, those treated with angiotensin II (ATII) had higher mortality rates compared to those receiving other vasopressors, although the difference was not statistically significant after adjusting for other factors.

Despite ATII's approval for increasing blood pressure in shock, the study found no significant improvement in hemodynamic response or mortality when used as a third-line treatment, with only 37.5% of ATII patients responding positively compared to 45.1% in the non-ATII group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Angiotensin II for Catecholamine Refractory Septic or Distributive Shock on Mortality: A Propensity Score Weighted Analysis of Real-World Experience in the Medical ICU. Quan, M., Cho, N., Bushell, T., et al.[2022]

In septic patients, lower levels of angiotensin II and AT-1 receptors are associated with septic shock and non-survivors, indicating their potential role as biomarkers for prognosis.

Angiotensin II and AT-2 levels show high sensitivity and specificity for identifying shock in septic patients, while the AT-1/AT-2 ratio may help predict mortality risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin II and angiotensin II receptor 2 levels can predict shock and mortality in septic patients. Ozer, AB., Bicakcioglu, M., Baykan, S., et al.[2022]

Angiotensin II (AT-II) was approved by the FDA in December 2017 for increasing blood pressure in adults experiencing septic or distributive shock, showing a significant response rate compared to placebo in a phase 3 study.

While AT-II effectively raised mean arterial pressure in patients already on norepinephrine, it did not significantly reduce mortality by day 28, indicating the need for further research on its safety and optimal use in shock therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Blast From the Past: Revival of Angiotensin II for Vasodilatory Shock. Bissell, BD., Browder, K., McKenzie, M., et al.[2019]

Angiotensin II (AT-II) has been recently approved by the FDA as a vasopressor to be used alongside other medications for treating refractory septic shock, which is a severe condition characterized by persistent low blood pressure despite fluid resuscitation.

Current literature suggests that while AT-II can help reduce the need for high doses of catecholamines in septic shock, further large-scale studies are needed to fully understand its effects on various body systems and potential risks, such as venous thromboembolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin II in septic shock. Jadhav, AP., Sadaka, FG.[2020]

In an animal study involving conscious ewes with induced hyperdynamic sepsis, angiotensin II infusion successfully restored arterial pressure but reduced renal blood flow significantly.

Despite the decrease in renal blood flow, angiotensin II infusion led to a remarkable increase in urine output (7-fold) and improved creatinine clearance by 70%, indicating its potential efficacy in managing renal function during hypotensive hyperdynamic sepsis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin II in experimental hyperdynamic sepsis. Wan, L., Langenberg, C., Bellomo, R., et al.[2021]

Angiotensin II (AT2) significantly improved mean arterial pressure (MAP) in patients with vasodilatory shock, achieving a response in 69.9% of those treated compared to only 23.4% in the placebo group, based on a Phase III trial with 321 participants.

While AT2 showed promise in increasing blood pressure, it did not significantly affect overall mortality rates, and its safety profile remains uncertain due to high rates of serious adverse events in both treatment and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of angiotensin II in treatment of refractory distributive shock. Rodriguez, R., Fernandez, EM.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of Angiotensin II for Catecholamine Refractory Septic or Distributive Shock on Mortality: A Propensity Score Weighted Analysis of Real-World Experience in the Medical ICU. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

Angiotensin II and angiotensin II receptor 2 levels can predict shock and mortality in septic patients. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A Blast From the Past: Revival of Angiotensin II for Vasodilatory Shock. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Angiotensin II in septic shock. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Angiotensin II in experimental hyperdynamic sepsis. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Role of angiotensin II in treatment of refractory distributive shock. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Myocardial effects of angiotensin II compared to norepinephrine in an animal model of septic shock. [2023]