Angiotensin II for Distributive Shock

Overseen By Choy Lewis, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Northwestern University

Must not be taking: Vasopressors

Disqualifiers: Pregnancy, Thromboembolic disease, others

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: Unknown

Duration: 24 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Angiotensin II to determine its effectiveness for patients experiencing distributive shock (a severe drop in blood pressure) shortly after heart transplants or left ventricular assist device (LVAD) placements. The study compares the effects of Angiotensin II with a placebo (an inactive treatment), alongside the usual care these patients receive. Participants will be divided into two groups based on whether they had a heart transplant or LVAD implant. The trial seeks individuals who have experienced distributive shock within 48 hours of these surgeries and are not currently using Angiotensin II as another treatment. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to understand how Angiotensin II 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, it mentions that the study drug must be used as a first line agent for distributive shock, which might affect your current treatment plan.

What is the safety track record for Angiotensin II (Giapreza)?

Research has shown that Angiotensin II, also known as Giapreza, has been studied for its safety in treating distributive shock. In a study with 321 adults, researchers found that the treatment was generally well-tolerated, with most patients not experiencing serious side effects. The study demonstrated that Angiotensin II can help increase blood pressure, which is crucial for patients in shock. While some side effects can occur, they are usually manageable. The treatment is already approved for use in septic shock, indicating a strong safety record. Overall, Angiotensin II appears to be a safe option, making it a promising choice for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Angiotensin II is unique because it targets the renin-angiotensin system to stabilize blood pressure in cases of distributive shock, which is often challenging to manage with standard treatments like norepinephrine or vasopressin. Unlike these common vasopressors, Angiotensin II directly acts on blood vessels to constrict them and increase blood pressure. Researchers are excited about this treatment because it offers a new mechanism of action, providing a potential alternative for patients who do not respond well to other vasopressors. Additionally, its rapid administration and adjustable dosing could make it a flexible and effective option in critical care settings.

What evidence suggests that Angiotensin II might be an effective treatment for distributive shock?

Research has shown that Angiotensin II, which participants in this trial may receive, can effectively raise blood pressure in patients with vasodilatory shock, a condition where blood vessels are too relaxed. One study found it helped patients reach their target blood pressure when other treatments were ineffective. Another study demonstrated that Angiotensin II allowed patients to reduce their use of other blood pressure medications. This suggests it can be an important option to stabilize patients with this type of shock. Although it did not lower the death rate, controlling blood pressure remains crucial for these patients. Overall, Angiotensin II has shown promising results in managing this serious condition. ^{2 6 7 8 9}

Who Is on the Research Team?

Choy Lewis, MD

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for adults who develop distributive shock within 48 hours after a heart transplant or left ventricular assist device (LVAD) placement. They must have specific blood pressure and resistance criteria met, with normal cardiac output. Pregnant or breastfeeding women, those unwilling to consent, patients already on vasopressors before surgery, or with preexisting thromboembolic disease or distributive shock are excluded.

Inclusion Criteria

I experienced shock soon after my heart transplant or VAD placement.

Exclusion Criteria

I have a condition where my blood flow is not normal, leading to low blood pressure.

I am allergic to certain blood pressure medications.

I have not used the study drug as the first treatment for my shock condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive Angiotensin II or placebo as a first-line vasopressor for vasoplegia

24 hours

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of acute kidney injury, stroke, and other secondary outcomes

48 hours

Extended Follow-up

Participants are monitored for long-term outcomes such as ICU and hospital length of stay, 30-day mortality, and allograft rejection

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Angiotensin II
• Placebo

Trial Overview The study tests Angiotensin II (Giapreza) against a placebo in managing low blood pressure due to distributive shock post-heart surgery. It's a small-scale test involving 40 patients split into two groups: one for heart transplants and another for LVAD implants, each further divided equally between the drug and placebo.

How Is the Trial Designed?

Group I: Treatment Active Control 1 Intervention

Angiotensin II administered as an intravenous (IV) infusion will be increased every 5 minutes by 5-10ng/kg/min increments up to 80ng/kg/min

Group II: Control Placebo Group 1 Intervention

Intravenous (IV) infusion (saline)

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?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

La Jolla Pharmaceutical Company

Industry Sponsor

Trials

24

Recruited

2,700+

Citations

1. giapreza.com giapreza.com/efficacy

Efficacy and Trial Design | GIAPREZA® (angiotensin II) GIAPREZA was studied in ATHOS-3, an international, randomized, double-blind, placebo-controlled study of 321 patients with distributive shock.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38888542/

ANGIOTENSIN II IN THE TREATMENT OF DISTRIBUTIVE ... While ATII did not reduce mortality among distributive shock patients, it allowed for significant adjunctive vasopressor reduction at 3 h without an increase ...

3. janesthanalgcritcare.biomedcentral.com janesthanalgcritcare.biomedcentral.com/articles/10.1186/s44158-024-00186-y

The use of angiotensin II for the management of distributive ... Clinical studies evaluating the use of ATII in critically ill patients with distributive shock reported promising results, with improvements ...

4. 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.

5. jmsma.scholasticahq.com jmsma.scholasticahq.com/article/131791-single-center-real-world-observational-analysis-of-angiotensin-ii-salvage-therapy-for-refractory-shock

Single-Center, Real-World Observational Analysis of ... Fourteen (67%) presented with distributive shock. At angiotensin-II initiation, 76% of patients were on at least three other vasopressors at a ...

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/PMC11328364/

The use of angiotensin II for the management of distributive ... ... shock [13]. In addition, ATII therapy appears to have a favorable safety profile, with minimal adverse effects reported in clinical trials.

8. 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 ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6205124/

Angiotensin II Brings More Questions Than Answers - PMC The recent approval of angiotensin II (ATII) gives clinicians a new tool for treating patients with septic shock. The drug is highly effective at improving ...