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| ID | Type | Description | Link |
|---|---|---|---|
| HL-051952 | Other Grant/Funding Number | National Heart, Lung, and Blood Institute | |
| AG070371 | Other Grant/Funding Number | National Institute on Aging |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| National Institute on Aging (NIA) | NIH |
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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Participants on ACE inhibitors | Experimental | Participants taking ACE inhibitors (angiotensin-converting enzyme inhibitors)will be placed into this group. Intervention: Drug: Angiotensin II. |
|
| Participants on ARBs | Experimental | Participants taking ARBs (angiotensin-receptor blockers) will be placed into this group. Intervention: 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Angiotensin II | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | up to 1 hour |
| Measure | Description | Time Frame |
|---|---|---|
| Median Serum Level of Bradykinin 1-8 | Median serum level of Bradykinin 1-8 | up to 1 hour |
| Median Serum Level of Bradykinin 1-7 | Median serum level of Bradykinin 1-7 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rohesh Fernando, MD | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wake Forest Baptist Medical Center | Winston-Salem | North Carolina | 27157 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15728043 | Background | 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. | |
| 21636935 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Participants on ACE Inhibitors | Participants taking ACE inhibitors (angiotensin-converting enzyme inhibitors)will be placed into this group. Intervention: Drug: Angiotensin II. 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. |
| FG001 | Participants on ARBs | Participants taking ARBs (angiotensin-receptor blockers) will be placed into this group. Intervention: Drug: Angiotensin II. 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. |
| FG002 | Other Classes of Antihypertensive Agents | Participants taking any other class of Antihypertensive Agents will be placed into this group. Intervention: Drug: Angiotensin II. 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Participants on ACE Inhibitors | Participants taking ACE inhibitors (angiotensin-converting enzyme inhibitors)will be placed into this group. Intervention: Drug: Angiotensin II. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | ACE Inhibitor Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol ARB Arm: 2 patients did not reach the treatment goal in this group and were therefore excluded from primary outcome analysis Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | ng/kg/min | up to 1 hour |
|
7 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Participants on ACE Inhibitors | Participants taking ACE inhibitors (angiotensin-converting enzyme inhibitors)will be placed into this group. Intervention: Drug: Angiotensin II. 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leg Swelling | Vascular disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rohesh J. Fernando, MD | Atrium Health Wake Forest Baptist | 336.716.2712 | rfernan@wakehealth.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 20, 2020 | Aug 6, 2025 | Prot_SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 17, 2024 | May 28, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000804 | Angiotensin II |
| C000627694 | Giapreza |
| ID | Term |
|---|---|
| D000809 | Angiotensins |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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|
|
| Up to 1 hour |
| Median Serum Level of Bradykinin 1-5 | Median serum level of Bradykinin 1-5 | Up to 1 hour |
| Median Serum Level of Aldosterone | Median serum level of Aldosterone | Up to 1 hour |
| Median Serum Level of Angiotensin I | Median serum level of Angiotensin I | Up to 1 hour |
| Median Serum Level of Angiotensin II | Median serum level of Angiotensin II | up to 1 hour |
| Median Serum Level of Angiotensin IV | Median serum level of Angiotensin IV | Up to 1 hour |
| Median Serum Level of Angiotensin 1-7 | Median serum level of Angiotensin 1-7 | Up to 1 hour |
| Median Serum Level of Angiotensin 1-5 | Median serum level of Angiotensin 1-5 | Up to 1 hour |
| Median Serum Level of Angiotensin 1-9 | Median serum level of Angiotensin 1-9 | Up to 1 hour |
| Median Serum Level of Angiotensin 2-10 | Median serum level of Angiotensin 2-10 | Up to 1 hour |
| Median Serum Level of Angiotensin 2-7 | Median serum level of Angiotensin 2-7 | Up to 1 hour |
| Median Serum Level of Angiotensin 3-7 | Median serum level of Angiotensin 3-7 | Up to 1 hour |
| Median Serum Level of Angiotensin 1-12 | Median serum level of Angiotensin 1-12 | Up to 1 hour |
| 28528561 | Background | 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. |
| 22319643 | Background | 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. |
| 25286986 | Background | 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. |
| 9416783 | Background | 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. |
| BG001 | Participants on ARBs | Participants taking ARBs (angiotensin-receptor blockers) will be placed into this group. Intervention: Drug: Angiotensin II. 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. |
| BG002 | Other Classes of Antihypertensive Agents | Participants taking any other class of Antihypertensive Agents will be placed into this group. Intervention: Drug: Angiotensin II. 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. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Participants on ARBs | Participants taking ARBs (angiotensin-receptor blockers) will be placed into this group. Intervention: Drug: Angiotensin II. 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. |
| OG002 | Other Classes of Antihypertensive Agents | Participants taking any other class of Antihypertensive Agents will be placed into this group. Intervention: Drug: Angiotensin II. 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. |
|
|
| Secondary | Median Serum Level of Bradykinin 1-8 | Median serum level of Bradykinin 1-8 | ACE Inhibitor Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Bradykinin 1-7 | Median serum level of Bradykinin 1-7 | ACE Inhibitor Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | Up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Bradykinin 1-5 | Median serum level of Bradykinin 1-5 | ACE Inhibitor Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | Up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Aldosterone | Median serum level of Aldosterone | ACE Inhibitor Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | Up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Angiotensin I | Median serum level of Angiotensin I | ACE Inhibitor Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | Up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Angiotensin II | Median serum level of Angiotensin II | ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Angiotensin IV | Median serum level of Angiotensin IV | ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | Up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Angiotensin 1-7 | Median serum level of Angiotensin 1-7 | ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | Up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Angiotensin 1-5 | Median serum level of Angiotensin 1-5 | ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | Up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Angiotensin 1-9 | Median serum level of Angiotensin 1-9 | ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | Up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Angiotensin 2-10 | Median serum level of Angiotensin 2-10 | ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | Up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Angiotensin 2-7 | Median serum level of Angiotensin 2-7 | ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | Up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Angiotensin 3-7 | Median serum level of Angiotensin 3-7 | ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol | Posted | Median | Inter-Quartile Range | pmol/L | Up to 1 hour |
|
|
|
| Secondary | Median Serum Level of Angiotensin 1-12 | Median serum level of Angiotensin 1-12 | ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol, 2 patients unable to get sample. ARBs Arm: 1 patient unable to get sample. Other Classes of Antihypertensive Agents: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol, 2 patients unable to get sample. | Posted | Median | Inter-Quartile Range | pmol/L | Up to 1 hour |
|
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 1 |
| 5 |
| EG001 | Participants on ARBs | Participants taking ARBs (angiotensin-receptor blockers) will be placed into this group. Intervention: Drug: Angiotensin II. 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. | 0 | 8 | 0 | 8 | 2 | 8 |
| EG002 | Other Classes of Antihypertensive Agents | Participants taking any other class of Antihypertensive Agents will be placed into this group. Intervention: Drug: Angiotensin II. 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. | 0 | 7 | 0 | 7 | 0 | 7 |
| Blurred Vision | Eye disorders | Systematic Assessment |
|
| Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | arthritic shoulder and arm pain from surgery positioning |
|
| Shortness of Breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D012898 | Autacoids |
| D018836 | Inflammation Mediators |
| D001685 | Biological Factors |