Angiotensin II for Low Blood Pressure During Surgery

Recruiting in Palo Alto (17 mi)

Overseen by Rohesh Fernando, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Wake Forest University Health Sciences

Must be taking: Ace inhibitors, Arbs

Disqualifiers: Obesity, Stroke, Heart failure, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

Hypotension in adult patients undergoing general anesthesia is common. This can lead to hypoperfusion of vital organs, organ damage, and states of increased metabolic duress. This may be worse in patients with underlying essential hypertension and worse in patients taking Angiotensin Converting Enzyme Inhibitors (ACE) and Angiotensin Receptor Blockers (ARBs). Intravenous (IV) administration of Ang II may be an effective treatment of hypotension in this patient population.

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 data supports the effectiveness of the drug Angiotensin II (Giapreza) for treating low blood pressure during surgery?

A case report showed that Angiotensin II (Giapreza) improved blood pressure in a patient with severe low blood pressure due to a drug overdose, suggesting it can help manage low blood pressure in challenging situations. ^{1 2 3 4 5}

Is Angiotensin II safe for use in humans during surgery?

There is limited safety data specifically for Angiotensin II during surgery, but related drugs acting on the renin-angiotensin system have been associated with low blood pressure during surgery. Some guidelines suggest stopping these drugs before surgery to avoid this risk, but the evidence is not definitive. ^{1 5 6 7 8}

How is the drug Angiotensin II (Giapreza) different from other treatments for low blood pressure during surgery?

Angiotensin II (Giapreza) is unique because it is a novel vasopressor (a drug that raises blood pressure) that can be used when other standard vasopressors are not effective, particularly in cases of vasodilatory shock. It works by directly constricting blood vessels, which can help improve blood pressure and reduce the need for other medications. ^{1 2 9 10 11}

Research Team

Rohesh Fernando, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

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.

I have had a heart attack or have cardiac stents.

You have a hard time breathing.

Trial Timeline

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

Treatment Details

Interventions

• Angiotensin II (Vasoconstrictor)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Dr. L. Ebony Boulware

Wake Forest University Health Sciences

Chief Medical Officer since 2022

MD from Duke University School of Medicine, MPH from Johns Hopkins Bloomberg School of Public Health

Dr. Julie Ann Freischlag

Wake Forest University Health Sciences

Chief Executive Officer since 2020

BS from University of Illinois, MD from Rush University

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Association of renin angiotensin antagonists with adverse perioperative events in patients undergoing elective orthopaedic surgery: a case-control study. [2018]

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Acute response to captopril as a predictive test for surgery in renovascular hypertension. [2018]

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

Prospective Randomized Evaluation of Preoperative Angiotensin-Converting Enzyme Inhibition (PREOP-ACEI). [2019]

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

Acute Bradykinin Receptor Blockade During Hemorrhagic Shock in Mice Prevents the Worsening Hypotensive Effect of Angiotensin-Converting Enzyme Inhibitor. [2018]

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

The hemodynamic effects of anesthetic induction in vascular surgical patients chronically treated with angiotensin II receptor antagonists. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Inhibition of vasoconstriction by angiotensin receptor antagonist GR117289C in arterial grafts. [2019]

8. Italy pubmed.ncbi.nlm.nih.gov

Chronic utilization of agents acting on the renin-angiotensin system and intraoperative arterial pressure. [2013]

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

Intraoperative cardiac arrest: was it the ACE inhibitor? [2014]

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

Treating anesthesia-induced hypotension by angiotensin II in patients chronically treated with angiotensin-converting enzyme inhibitors. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Use of Angiotensin II for Post Cardiopulmonary Bypass Vasoplegic Syndrome. [2019]