Angiotensin-II for Vasodilatory Shock

Enrolling by invitation at 1 trial location

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Todd Sweberg

Must not be taking: Ace inhibitors, Arbs

Disqualifiers: DNR/DNI, Cardiogenic shock, ECMO, 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: 1

Duration: 24 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Angiotensin-II, a drug, to determine its effectiveness in helping children with vasodilatory shock, a condition where blood vessels widen excessively, leading to low blood pressure. Researchers aim to assess whether this drug can safely increase blood pressure and reduce the need for other medications. Children who have received fluids for shock but still experience low blood pressure might be suitable candidates. Participants will receive Angiotensin-II alongside their usual care, and researchers will closely monitor their health for changes. 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 does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using an angiotensin converting enzyme inhibitor or angiotensin receptor blocker.

What is the safety track record for Angiotensin-II?

Research has shown that Angiotensin-II effectively raises blood pressure in patients with vasodilatory shock who don't respond to other treatments. It reduces the need for additional medications, suggesting it is well-tolerated and could lead to fewer side effects from other drugs.

The FDA has approved Angiotensin-II for treating vasodilatory shock in adults, indicating a well-understood safety profile. Although it hasn't been shown to reduce overall death rates, it shows promise in effectively managing blood pressure.

This trial focuses on children, so the safety information from adult studies might not fully apply. However, existing research provides a helpful starting point to understand how Angiotensin-II might work in children. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for vasodilatory shock, which often include catecholamines and vasopressin, Angiotensin-II works by directly activating the angiotensin receptors to constrict blood vessels and increase blood pressure. This unique mechanism can be particularly effective when other treatments fail to stabilize blood pressure. Researchers are excited about Angiotensin-II because it offers a targeted approach that could rapidly improve blood pressure control, especially in patients who don't respond well to existing therapies.

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

Research has shown that Angiotensin-II, the treatment under study in this trial, can effectively raise blood pressure in patients with vasodilatory shock, especially when other treatments fail. In one study, 15 out of 21 patients had their blood pressure return to normal after receiving Angiotensin-II. Another study found that it reduced the need for other blood pressure medications within just three hours. Although it did not lower death rates in patients with distributive shock, it improved blood pressure and reduced the need for additional medications. This suggests Angiotensin-II could be a valuable treatment for managing blood pressure in vasodilatory shock. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for pediatric patients with a condition called vasodilatory shock, who haven't improved after receiving fluids. They should be stable enough to receive an experimental treatment and participate in follow-up assessments.

Inclusion Criteria

Indwelling arterial and central venous lines

Parent or legal guardian is willing and able to provide informed consent and assist the patient in complying with all protocol requirements

I've been on blood pressure meds for 2+ hours but still have very low blood pressure.

Exclusion Criteria

Prisoners

Cannulated to extracorporeal membrane oxygenation

Pre-existing condition confounding outcome determination such as terminal illness

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive Angiotensin-II in addition to standard of care therapy for vasodilatory shock. The study team monitors vital signs, blood work, and potential side effects.

24 hours

Continuous monitoring

Follow-up

A follow-up phone call to check in with the patient will be performed 28 days after enrollment. Monitoring includes changes in renal resistive index, serum cytokine levels, and other parameters.

28 days

1 phone call

What Are the Treatments Tested in This Trial?

Interventions

• Angiotensin-II

Trial Overview The trial tests the safety and effectiveness of Angiotensin-II, added to standard care, in raising blood pressure or reducing the need for other blood pressure medications. Patients' vitals and kidney blood flow will be monitored, followed by a check-in call after 28 days.

How Is the Trial Designed?

Group I: Pediatric patients in vasodilatory shock Experimental Treatment 1 Intervention

Patients enrolled in the study who meet inclusion criteria will receive Angiotensin-II per the titration protocol.

Who Is Running the Clinical Trial?

Todd Sweberg

Lead Sponsor

Innoviva Specialty Therapeutics

Industry Sponsor

Trials

3

Recruited

180+

Citations

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

How Effective is Angiotensin II in Decreasing Mortality of ... Ang-2 is found to be able to normalize blood pressure in 15 patients out of 21 subjects in the previous study.,. This systematic review aims to ...

2. journals.lww.com journals.lww.com/shockjournal/fulltext/2024/08000/angiotensin_ii_in_the_treatment_of_distributive.2.aspx

angiotensin ii in the treatment of distributive shock: a ... Conclusions: While ATII did not reduce mortality among distributive shock patients, it allowed for significant adjunctive vasopressor reduction at 3 h without ...

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. giapreza.com giapreza.com/efficacy

Efficacy and Trial Design | GIAPREZA® (angiotensin II) Primary endpoint2: An increase in MAP at Hour 3 of at least 10 mmHg, or a MAP response of ≥75 mmHg, without an increase in baseline vasopressor dosing.

5. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-023-04446-1

an exploratory post-hoc analysis of the ATHOS-3 clinical trial High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39337869/

Clinical Outcomes of Angiotensin II Therapy in Vasoplegic ... In vasodilatory shock, angiotensin II use demonstrated comparable in-hospital mortality compared to standard therapy.