Angiotensin II for Septic Shock

(ANGIO-ED Trial)

Overseen By Brett Faine, PharmD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Iowa

Must be taking: Norepinephrine, Antibiotics

Disqualifiers: Acute coronary syndrome, Cardiogenic shock, Mesenteric ischemia, Aortic dissection, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 6 hours

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called angiotensin II (Giapreza) for individuals with septic shock, a serious condition where infection causes dangerously low blood pressure. Researchers aim to determine if administering this treatment early in the emergency department can stabilize patients. It targets those needing ongoing medication to maintain blood pressure despite receiving fluids. Candidates include those receiving antibiotics for infection and requiring strong blood pressure support. As a Phase 4 trial, this research seeks to understand how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are actively taking two vasoactive agents, you would not be eligible to participate.

What is the safety track record for Angiotensin II?

Research has shown that angiotensin II has been tested for safety in people with septic shock. In one study, 321 adults with septic shock received this treatment. The results indicated that angiotensin II is generally safe, with most patients not experiencing serious side effects. Some common side effects included a slight increase in blood pressure and other mild reactions.

The FDA has approved the treatment for raising blood pressure in adults with certain types of shock. This approval indicates its safety for similar conditions. However, since every patient is different, discussing any possible risks with a doctor is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for septic shock, which typically include vasopressors like norepinephrine and vasopressin to stabilize blood pressure, Angiotensin II offers a unique mechanism by directly targeting angiotensin receptors to increase blood pressure. This direct action can help restore blood pressure more effectively in patients who are unresponsive to other vasopressors. Researchers are excited because Angiotensin II may provide a quicker and more efficient option to manage septic shock, potentially improving outcomes for critically ill patients.

What evidence suggests that angiotensin II might be an effective treatment for septic shock?

Studies have shown that angiotensin II, administered as an infusion in this trial, effectively raises blood pressure in patients with vasodilatory shock, even when other treatments have been ineffective. Research indicates that angiotensin II may extend the lives of patients with septic shock, particularly with early treatment. Some evidence suggests it can also reduce hospital stays for patients in shock. Overall, angiotensin II is approved and proven effective for treating vasodilatory shock, suggesting potential benefits for septic shock as well. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for a small group of 20 patients who arrive at the emergency department with septic shock and need immediate support to maintain blood pressure. Participants must be in a condition where they can receive angiotensin II within three hours after starting norepinephrine, a common drug used to treat low blood pressure.

Inclusion Criteria

I need norepinephrine to maintain my blood pressure after receiving enough fluids.

I am currently on IV antibiotics or will be starting them soon.

Can provide written informed consent (or legally authorized representative)

Exclusion Criteria

Expected lifespan of <12 hours

I am currently taking two medications to control my blood pressure.

I have had a condition where my intestines did not get enough blood.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive intravenous angiotensin II infusion for blood pressure support in the emergency department

Up to 6 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 day

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Angiotensin II

Trial Overview The study is testing if giving angiotensin II early on can help treat septic shock in patients who have just arrived at the emergency department. It's a pilot study, which means it's an initial test before larger studies are done.

How Is the Trial Designed?

Group I: Angiotensin II Infusion Experimental Treatment 1 Intervention

Angiotensin II is already approved in United States for the following indications:

Approved in United States as Giapreza for:

• Septic shock
• Vasodilatory shock

Who Is Running the Clinical Trial?

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Brett A Faine

Lead Sponsor

Trials

2

Recruited

60+

Published Research Related to This Trial

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]

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 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]

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 (Giapreza) was successfully used to treat vasodilation caused by a tricyclic overdose, improving hemodynamic parameters in the patient.

This novel application of angiotensin II may allow for lower doses of other vasopressors, potentially enhancing patient outcomes in cases of vasodilatory shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Patient With Tricyclic Antidepressant Overdose With Catecholamine-Resistant Hypotension Rescued With Angiotensin II: A Case Report. Ferdowsali, J., Ferdowsali, K.[2021]

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]

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]

Citations

1. giapreza.com giapreza.com/efficacy

Efficacy and Trial Design | GIAPREZA® (angiotensin II) Survival Data · Increased patient survival at day 28 · Survival benefit was greatest when initiated with lower vasopressor doses · DON'T WAIT—start GIAPREZA sooner ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9830054/

How Effective is Angiotensin II in Decreasing Mortality of ... The average length of stay in non-shock patient is 3–7 days comparing with shock patient is 16.5 days. The use of Ang-2 showed the potential to ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1704154

Angiotensin II for the Treatment of Vasodilatory Shock Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05193370

Angiotensin II vs. Vasopressin in Septic Shock While more studies are needed, preliminary data suggest that the vasopressor angiotensin II (AngII) may improve outcomes in septic shock. This study is a pilot ...

5. annalsofintensivecare.springeropen.com annalsofintensivecare.springeropen.com/articles/10.1186/s13613-025-01522-3

Angiotensin II, conventional vasopressor therapy, and ... Results. Overall 30-day mortality was 56.4%. Groups statistically differed by all baseline variables. In multivariable logistic regression, Ang ...

6. giapreza.com giapreza.com/safety

Safety & Adverse Events | GIAPREZA® (angiotensin II) The safety of GIAPREZA was evaluated in 321 adults with septic or other distributive shock in a randomized, double-blind, placebo-controlled study, ATHOS-3.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10882873/

Angiotensin II therapy in refractory septic shock Promising results have been observed in treating refractory hypotension with angiotensin II, which has been shown to increase mean arterial pressure.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05193370

Angiotensin II vs. Vasopressin in Septic Shock While more studies are needed, preliminary data suggest that the vasopressor angiotensin II (AngII) may improve outcomes in septic shock.

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/209360Orig1s000SumR.pdf

209360Orig1s000 - accessdata.fda.gov The results of ATHOS-3 constitute substantial evidence of the effectiveness of angiotensin II for increasing blood pressure in adults with ...