Angiotensin II in General Anesthesia

Hypertension Clinical Trial

Official title:

A Dose Finding Trial for Angiotensin II in Hypertensive Adults on Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers With Anesthesia-Mediated Hypotension

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03733145
• Other study ID #: IRB00054661
• Status: Recruiting
• Phase: Phase 1
• Start date: October 3, 2019
• Est. completion date: December 2026

Study information

• Verified date: April 2024
• Source: Wake Forest University Health Sciences
• Contact: Rohesh Fernando, MD
• Phone: 3367162712
• Email: rfernan[@]wakehealth.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Hypotension in adult patients undergoing general anesthesia is common. Many of the body's normal mechanisms to maintain adequate blood pressure in the non-anesthetized state are significantly altered by anesthetic agents, which may lead to hypotension. This can lead to hypoperfusion of vital organs, organ damage, and states of increased metabolic duress. In response to this it has become standard of care to attempt to maintain blood pressure levels within 20% of baseline in most patients under anesthesia. Maintaining the baseline blood pressure is important as patients may have pathology such as coronary artery disease, carotid stenosis, and renal artery stenosis, and hypotension may compromise the perfusion of these organs. Vasodilation also plays a key role in hypotension due to general anesthesia. Therefore, the intravenous (IV) administration of Ang II may be an effective treatment of hypotension in this patient population.The objective of this study is to determine the infusion rate of Ang II that is necessary to return systolic blood pressure (SBP) to within 5% of baseline or greater in patients with essential hypertension taking ACE inhibitors, ARBs, or different classes of antihypertensive agents and further to determine the plasma levels of different RAAS components

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of hypertension and treatment with at least one medication including an ACE inhibitor, ARB, and other agents for greater than 2 months
• Patients undergoing general anesthesia

Exclusion Criteria:

• BMI > 40
• History of deep venous thrombosis / thromboembolic disease
• History of stroke,
• Baseline SBP of = 160 mmHg,
• History of myocardial infarction or cardiac stents
• Difficult airway
• Asthma
• Congestive heart failure
• Chronic obstructive pulmonary disease
• Pregnant patients

Related Conditions & MeSH terms

• Hypertension
• Hypotension

Intervention

Drug:
• Angiotensin II
Participants in the ACE inhibitors, ARBs, and Other Classes of Antihypertensive Agents who's systolic blood pressure (SBP) is less than 80% of the baseline reading is detected, will have Ang II initiated at 2 ng/kg/min through a peripheral IV. The infusion will be increased at the discretion of the clinical team based on the response of the patient until a SBP within 5% of the baseline SBP.

Locations

Country	Name	City	State
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

References & Publications (6)

Chawla LS, Busse L, Brasha-Mitchell E, Davison D, Honiq J, Alotaibi Z, Seneff MG. Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Crit Care. 2014 Oct 6;18(5):534. doi: 10.1186/s13054-014-0534-9. — View Citation

Comfere T, Sprung J, Kumar MM, Draper M, Wilson DP, Williams BA, Danielson DR, Liedl L, Warner DO. Angiotensin system inhibitors in a general surgical population. Anesth Analg. 2005 Mar;100(3):636-644. doi: 10.1213/01.ANE.0000146521.68059.A1. — View Citation

Ferreira AJ, Murca TM, Fraga-Silva RA, Castro CH, Raizada MK, Santos RA. New cardiovascular and pulmonary therapeutic strategies based on the Angiotensin-converting enzyme 2/angiotensin-(1-7)/mas receptor axis. Int J Hypertens. 2012;2012:147825. doi: 10.1155/2012/147825. Epub 2012 Jan 26. — View Citation

Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, Busse LW, Altaweel L, Albertson TE, Mackey C, McCurdy MT, Boldt DW, Chock S, Young PJ, Krell K, Wunderink RG, Ostermann M, Murugan R, Gong MN, Panwar R, Hastbacka J, Favory R, Venkatesh B, Thompson BT, Bellomo R, Jensen J, Kroll S, Chawla LS, Tidmarsh GF, Deane AM; ATHOS-3 Investigators. Angiotensin II for the Treatment of Vasodilatory Shock. N Engl J Med. 2017 Aug 3;377(5):419-430. doi: 10.1056/NEJMoa1704154. Epub 2017 May 21. — View Citation

Singh A, Antognini JF. Perioperative hypotension and myocardial ischemia: diagnostic and therapeutic approaches. Ann Card Anaesth. 2011 May-Aug;14(2):127-32. doi: 10.4103/0971-9784.81569. — View Citation

Tallarida RJ, Stone DJ Jr, Raffa RB. Efficient designs for studying synergistic drug combinations. Life Sci. 1997;61(26):PL 417-25. doi: 10.1016/s0024-3205(97)01030-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean dose required to increase the SBP	The mean dose required to increase the SBP in these 3 cohorts with essential hypertension (ACE inhibitor, ARB, or those on another class of hypertensive agents) to within 5% of baseline or higher will be calculated.	up to 1 hour
Secondary	Mean value of Bradykinin	Mean values of Bradykinin 1-8 and Bradykinin 1-7 will be calculated and reported.	up to 1 hour
Secondary	Mean value of Angiontensin	Mean values of Angiotensin I, Angiotensin II, Angiotensin IV, Angiotensin 1-7, Angiotensin 1-5, Angiotensin 1-9, Angiotensin 2-10, Angiotensin 2-7, and Angiotensin 3-7 will be calculated and reported.	up to 1 hour
Secondary	Mean value of Aldosterone	Mean value of Aldosterone will be calculated and reported.	up to 1 hour