HypertensionPhase 4NCT03733145
Angiotensin II in General Anesthesia
A Phase 4 study testing Angiotensin II in people with Hypertension, run by Wake Forest University Health Sciences at 1 site in United States.
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)… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Hypertension
- What is being tested?
- Angiotensin II
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Oct 2019to 21 Mar 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- Asthma
- Congestive heart failure
- Chronic obstructive pulmonary disease
- Pregnant patients
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
About this study
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
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.
Read the detailed 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
- Conditions
- Hypertension
- Being tested
- Angiotensin II
- Keywords
- Angiotensin II, Angiotensin Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, Anesthesia-Mediated Hypotension
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin IIDrug
Also called Ang II, Giapreza
Participants in the ACE inhibitors, angiotensin-receptor blockers (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.
| Study group | Role | What they receive |
|---|---|---|
| Participants on ACE inhibitors | Experimental | Participants taking ACE inhibitors (angiotensin-converting enzyme inhibitors)will be placed into this group. Intervention: Drug: Angiotensin II. Receives: Drug: Angiotensin II |
| Participants on ARBs | Experimental | Participants taking ARBs (angiotensin-receptor blockers) will be placed into this group. Intervention: Drug: Angiotensin II. Receives: Drug: Angiotensin II |
| Other Classes of Antihypertensive Agents | Experimental | Participants taking any other class of Antihypertensive Agents will be placed into this group. Intervention: Drug: Angiotensin II. Receives: Drug: Angiotensin II |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Dose Required to Increase the Systolic Blood Pressure (SBP)
The median 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.
Measured: up to 1 hour
Secondary outcomes (14)
Median Serum Level of Bradykinin 1-8
Median serum level of Bradykinin 1-8
Measured: up to 1 hour
Median Serum Level of Bradykinin 1-7
Median serum level of Bradykinin 1-7
Measured: Up to 1 hour
Median Serum Level of Bradykinin 1-5
Median serum level of Bradykinin 1-5
Measured: Up to 1 hour
Median Serum Level of Aldosterone
Median serum level of Aldosterone
Measured: Up to 1 hour
Median Serum Level of Angiotensin I
Median serum level of Angiotensin I
Measured: Up to 1 hour
Median Serum Level of Angiotensin II
Median serum level of Angiotensin II
Measured: up to 1 hour
Median Serum Level of Angiotensin IV
Median serum level of Angiotensin IV
Measured: Up to 1 hour
Median Serum Level of Angiotensin 1-7
Median serum level of Angiotensin 1-7
Measured: Up to 1 hour
Median Serum Level of Angiotensin 1-5
Median serum level of Angiotensin 1-5
Measured: Up to 1 hour
Median Serum Level of Angiotensin 1-9
Median serum level of Angiotensin 1-9
Measured: Up to 1 hour
Median Serum Level of Angiotensin 2-10
Median serum level of Angiotensin 2-10
Measured: Up to 1 hour
Median Serum Level of Angiotensin 2-7
Median serum level of Angiotensin 2-7
Measured: Up to 1 hour
Median Serum Level of Angiotensin 3-7
Median serum level of Angiotensin 3-7
Measured: Up to 1 hour
Median Serum Level of Angiotensin 1-12
Median serum level of Angiotensin 1-12
Measured: Up to 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2018
- Study start3 Oct 2019
- Primary completion21 Mar 2023
- Study completion21 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Rohesh Fernando, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03733145
- Sponsor's protocol ID
- IRB00054661
- Other IDs
- HL-051952, AG070371
- Status last verified
- Apr 2025
- First submitted
- 5 Nov 2018
- Last updated
- 24 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 15728043Singh 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.
PubMed 21636935Khanna 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.
PubMed 28528561Ferreira 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.
PubMed 22319643Chawla 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.
PubMed 25286986Tallarida 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.
PubMed 9416783
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03733145
- Acronym / sponsor ID
- IRB00054661
- Conditions
- Hypertension
- Keywords
- Angiotensin II, Angiotensin Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, Anesthesia-Mediated Hypotension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Institute on Aging (NIA)
- Study start
- 3 Oct 2019 (actual)
- Primary completion
- 21 Mar 2023 (actual)
- Study completion
- 21 Mar 2023 (actual)
- First posted
- 7 Nov 2018 (actual)
- Results
- Posted 24 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Participants on ACE inhibitors | Experimental | Drug: Angiotensin IIParticipants taking ACE inhibitors (angiotensin-converting enzyme inhibitors)will be placed into this group. Intervention: Drug: Angiotensin II. |
| Participants on ARBs | Experimental | Drug: Angiotensin IIParticipants taking ARBs (angiotensin-receptor blockers) will be placed into this group. Intervention: Drug: Angiotensin II. |
| Other Classes of Antihypertensive Agents | Experimental | Drug: Angiotensin IIParticipants taking any other class of Antihypertensive Agents will be placed into this group. Intervention: Drug: Angiotensin II. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (10 listed)
- BMI > 40
- History of deep venous thrombosis / thromboembolic disease
- History of stroke,
- Baseline SBP of ≥ 160 mmHg,
- History of myocardial infarction or cardiac stents
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Angiotensin IIAlso: Ang II, GiaprezaParticipants in the ACE inhibitors, angiotensin-receptor blockers (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. | Drug | Other Classes of Antihypertensive Agents, Participants on ACE inhibitors, Participants on ARBs |
Primary outcome
Median Dose Required to Increase the Systolic Blood Pressure (SBP)
Time frame: up to 1 hour
The median 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.
14 secondary outcomes
Median Serum Level of Bradykinin 1-8
Time frame: up to 1 hour
Median Serum Level of Bradykinin 1-7
Time frame: Up to 1 hour
Median Serum Level of Bradykinin 1-5
Time frame: Up to 1 hour
Median Serum Level of Aldosterone
Time frame: Up to 1 hour
Median Serum Level of Angiotensin I
Time frame: Up to 1 hour
Median Serum Level of Angiotensin II
Time frame: up to 1 hour
Median Serum Level of Angiotensin IV
Time frame: Up to 1 hour
Median Serum Level of Angiotensin 1-7
Time frame: Up to 1 hour
Median Serum Level of Angiotensin 1-5
Time frame: Up to 1 hour
Median Serum Level of Angiotensin 1-9
Time frame: Up to 1 hour
Median Serum Level of Angiotensin 2-10
Time frame: Up to 1 hour
Median Serum Level of Angiotensin 2-7
Time frame: Up to 1 hour
Median Serum Level of Angiotensin 3-7
Time frame: Up to 1 hour
Median Serum Level of Angiotensin 1-12
Time frame: Up to 1 hour
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15728043Comfere 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.
- Background: PubMed 21636935Singh 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.
- Background: PubMed 28528561Khanna 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.
- Background: PubMed 22319643Ferreira 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.
- Background: PubMed 25286986Chawla 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.
- Background: PubMed 9416783Tallarida 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rohesh Fernando, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Angiotensin II in people with Hypertension, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Dose Required to Increase the Systolic Blood Pressure (SBP) (time frame: up to 1 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03733145, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2025.