Angiotensin II for Low Blood Pressure During Surgery

Overseen By Thomas Templeton, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Wake Forest University Health Sciences

Must be taking: Ace inhibitors, Arbs

Disqualifiers: Obesity, Stroke, Heart failure, 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: 1

Duration: up to 1 hour

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Angiotensin II, a type of medication, can prevent low blood pressure in patients with high blood pressure undergoing surgery. Low blood pressure during surgery can harm vital organs, especially in those taking medications like ACE inhibitors or ARBs. The trial includes different groups based on the type of blood pressure medication participants use. Individuals with high blood pressure who have been on medications such as ACE inhibitors, ARBs, or similar drugs for over two months and are scheduled for surgery may be suitable for this trial. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits 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. However, since it includes patients already on certain blood pressure medications, you might be able to continue them. Please confirm with the trial coordinators.

What is the safety track record for Angiotensin II?

Research has shown that Angiotensin II is generally safe for use during surgery. Studies have found it to be well-tolerated by patients undergoing various surgeries, including those on the kidney, liver, heart, and lungs. Although some patients have experienced irregular heartbeats during surgery, medical teams carefully monitor these occurrences.

The FDA has already approved Angiotensin II for treating certain types of low blood pressure, indicating its safety when used properly. In small studies and reports, patients treated with Angiotensin II have not shown major side effects, suggesting it could be a safe option for managing low blood pressure during surgery. However, discussing any concerns with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Angiotensin II for treating low blood pressure during surgery because it works differently from standard treatments like vasopressors. While traditional options often stimulate adrenergic receptors to raise blood pressure, Angiotensin II directly constricts blood vessels by mimicking a natural hormone in the body responsible for regulating blood pressure. This unique mechanism can offer a more targeted approach, potentially reducing the risk of side effects associated with other medications. Plus, its rapid onset can be particularly beneficial during surgery when quick blood pressure control is crucial.

What is the effectiveness track record for Angiotensin II in treating low blood pressure during surgery?

Research has shown that Angiotensin II effectively treats low blood pressure during surgery. Studies have found that it can quickly raise blood pressure to safe levels. In this trial, participants will be divided into groups based on their current antihypertensive medications, such as ACE inhibitors, ARBs, or other classes, and will receive Angiotensin II. Previous findings suggest that Angiotensin II effectively manages low blood pressure, especially in patients taking medications like ACE inhibitors or ARBs. This treatment supports blood pressure without causing severe side effects. Overall, it has proven to be a reliable option for managing blood pressure issues during surgery. ^{1 3 4 6 7}

Who Is on the Research Team?

Rohesh Fernando, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults with high blood pressure who are undergoing general anesthesia and have been treated with blood pressure medications, including ACE inhibitors or ARBs, for over two months. It's not suitable for individuals with asthma, severe obesity (BMI > 40), pregnant women, those with a history of serious heart or lung conditions, stroke, deep vein thrombosis or difficult airways.

Inclusion Criteria

I will be put to sleep for surgery.

I have been treated for high blood pressure with medication for over 2 months.

Exclusion Criteria

I have chronic obstructive pulmonary disease.

You have a hard time breathing.

I have had a heart attack or have cardiac stents.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous (IV) administration of Angiotensin II to manage hypotension during general anesthesia

up to 1 hour

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Angiotensin II

Trial Overview The study is testing the effectiveness of intravenous Angiotensin II as a treatment for low blood pressure that occurs during general anesthesia in patients who already have high blood pressure and are on certain medications.

How Is the Trial Designed?

Group I: Participants on ARBs Experimental Treatment 1 Intervention

Participants taking ARBs (angiotensin-receptor blockers) will be placed into this group. Intervention: Drug: Angiotensin II.

Group II: Participants on ACE inhibitors Experimental Treatment 1 Intervention

Participants taking ACE inhibitors (angiotensin-converting enzyme inhibitors)will be placed into this group. Intervention: Drug: Angiotensin II.

Group III: Other Classes of Antihypertensive Agents Experimental Treatment 1 Intervention

Participants taking any other class of Antihypertensive Agents will be placed into this group. Intervention: Drug: Angiotensin II.

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?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

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]

A single oral dose of captopril significantly reduced blood pressure in 26 patients with renovascular disease, indicating its effectiveness as an acute angiotensin-converting enzyme (ACE) inhibitor.

The blood pressure response to captopril was predictive of postoperative outcomes, with a strong correlation between preoperative captopril-induced blood pressure changes and postoperative blood pressure levels, suggesting it could be a useful tool for anticipating surgical results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute response to captopril as a predictive test for surgery in renovascular hypertension. Salvetti, A., Arzilli, F., Nuccorini, A., et al.[2018]

Acute blockade of B2 receptors using icatibant significantly prevents blood pressure drops in mice treated with angiotensin-converting enzyme inhibitors during hemorrhagic shock, indicating a potential protective mechanism.

The study shows that B2 receptor blockade can rapidly and effectively mitigate the harmful hemodynamic effects associated with angiotensin-converting enzyme inhibitor treatment, which could be beneficial for patients undergoing emergency anesthesia or resuscitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Bradykinin Receptor Blockade During Hemorrhagic Shock in Mice Prevents the Worsening Hypotensive Effect of Angiotensin-Converting Enzyme Inhibitor. Charbonneau, H., Buléon, M., Minville, V., et al.[2018]

Angiotensin II, a newly approved vasopressor, was successfully used to treat a patient with post-cardiopulmonary bypass vasoplegic syndrome who did not respond to standard vasopressors and other treatments.

The patient showed significant improvement, being extubated within 24 hours and meeting important recovery metrics, highlighting the efficacy of Angiotensin II in severe cases of vasodilatory shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Angiotensin II for Post Cardiopulmonary Bypass Vasoplegic Syndrome. Evans, A., McCurdy, MT., Weiner, M., et al.[2019]

Patients receiving renin angiotensin antagonists (RAA) during elective surgeries had a significantly higher incidence of intraoperative hypotension (76.0% vs 45.9%) and acute kidney injury (11.6% vs 1.6%) compared to those not on RAA, indicating potential safety concerns.

The study also found that RAA use was associated with a higher rate of major adverse cardiac or cerebrovascular events (6.2% vs 0%), suggesting that RAA may increase the risk of serious complications during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of renin angiotensin antagonists with adverse perioperative events in patients undergoing elective orthopaedic surgery: a case-control study. Zainudheen, A., Scott, IA., Caney, X.[2018]

In a study of 14 patients with severe hypotension during anesthetic induction, an intravenous bolus of 2.5 micrograms of angiotensin II effectively increased systolic arterial pressure from 78 mm Hg to 152 mm Hg within 60 seconds.

While angiotensin II successfully restored blood pressure, it also caused a temporary impairment in left ventricular function, indicated by changes in heart metrics such as end-diastolic area and fiber-shortening velocity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating anesthesia-induced hypotension by angiotensin II in patients chronically treated with angiotensin-converting enzyme inhibitors. Eyraud, D., Mouren, S., Teugels, K., et al.[2019]

The study involving 208 isolated human internal mammary artery rings from 64 patients showed that the angiotensin receptor antagonist GR117289C can induce significant relaxation in arteries precontracted by angiotensin II, suggesting its potential to alleviate graft spasm during coronary artery bypass surgery.

GR117289C demonstrated a noncompetitive blockade of the AT1 receptor and also showed significant relaxation effects on arteries contracted by U46619, indicating it may also affect the thromboxane A2 receptor, making it a promising alternative treatment for graft spasm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of vasoconstriction by angiotensin receptor antagonist GR117289C in arterial grafts. Liu, MH., Floten, HS., Furnary, AP., et al.[2019]

Patients treated with angiotensin II receptor antagonists (ARA) experienced significantly higher rates of hypotension after anesthesia induction compared to those treated with beta-blockers/calcium channel blockers (BB/CB) or angiotensin-converting enzyme inhibitors (ACEI), with all 12 ARA patients experiencing hypotension.

The ARA group required more ephedrine to manage hypotension and had cases of refractory hypotension that were successfully treated with a vasopressin system agonist, highlighting the need for careful management of blood pressure in these patients during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The hemodynamic effects of anesthetic induction in vascular surgical patients chronically treated with angiotensin II receptor antagonists. Brabant, SM., Bertrand, M., Eyraud, D., et al.[2022]

In a study of 756 surgical patients, chronic use of agents acting on the renin-angiotensin system (ARAS) was not linked to increased episodes of intraoperative hypotension, suggesting that continuing ARAS medication may be safe during surgery.

The study found that while intraoperative hypertension was more common in patients taking ARAS, there was no significant difference in hypotension episodes between those who stopped ARAS before surgery and those who continued it, indicating that the current recommendation for transient discontinuation may need reevaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic utilization of agents acting on the renin-angiotensin system and intraoperative arterial pressure. Castanheira, L., de Lurdes Castro, M., Calheiros, J.[2013]

Omitting the final preoperative dose of angiotensin-converting enzyme inhibitors (ACEIs) significantly reduced the occurrence of intraoperative hypotension in patients undergoing noncardiac, nonvascular surgeries, with a decrease from 69% in the continuation group to 55% in the omission group.

While the omission of ACEIs led to fewer intraoperative hypotensive events, it also resulted in a higher incidence of postoperative hypertensive episodes, indicating a need for careful management of blood pressure after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Randomized Evaluation of Preoperative Angiotensin-Converting Enzyme Inhibition (PREOP-ACEI). Shiffermiller, JF., Monson, BJ., Vokoun, CW., et al.[2019]

Continuing angiotensin-converting enzyme (ACE) inhibitor therapy on the day of surgery can lead to significant intraoperative hypotension, as demonstrated by a case where a patient experienced cardiac arrest after taking her medication before surgery.

In a subsequent surgery with the same anesthetic management, withholding blood pressure medications on the day of surgery prevented hypotension, highlighting the importance of managing these medications to ensure patient safety during surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative cardiac arrest: was it the ACE inhibitor? Bjerregaard, J., Jaffe, RA.[2014]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12190507/

Angiotensin Receptor Blockade Does Not Decrease ... Hypotension during the perioperative KT period was defined according to our institutional protocol as an SBP < 120 mmHg. Our kidney transplant ...

2. bjanaesthesia.org.uk bjanaesthesia.org.uk/article/S0007-0912(24)00312-X/fulltext

Angiotensin II treatment of hypotension in noncardiac surgery Ang II was titrated every minute until SBP was within 5% of baseline. The infusion rate was not increased by more than 15 ng kg−1 min−1 at a ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04529005?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(GIAPREZA))&rank=3

Study Details | Angiotensin II in the Perioperative ... Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex ...

4. mdpi.com mdpi.com/2227-9059/12/8/1817

Angiotensin II as a Vasopressor for Perioperative ... Safety outcomes include incidence of thromboembolism within 48 h of the end of surgery and severe hypertension.

5. journals.lww.com journals.lww.com/ccejournal/fulltext/2022/05000/protocol_compliance_guiding_angiotensin_ii_use_in.11.aspx

Protocol Compliance Guiding Angiotensin II Use in Post... The Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) study demonstrated that administration of Ang II supports low blood pressure and reduces ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/05/NCT04529005/Prot_SAP_000.pdf

Angiotensin II in the Perioperative Management of ... The safety endpoints that will be captured will include: incidence of intraoperative arrhythmias for those who receive study drug ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S095281802400028X

Effect of continuing angiotensin-converting enzyme ... Intraoperative hypotension during non-cardiac surgery has been linked to elevated risks of adverse outcomes and mortality [9,10]. Specifically, myocardial ...