NCT03733145

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at below P25 for phase_4 hypertension

Timeline
Completed

Started Oct 2019

Typical duration for phase_4 hypertension

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 5, 2018

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 7, 2018

Completed
11 months until next milestone

Study Start

First participant enrolled

October 3, 2019

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 21, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 21, 2023

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

August 24, 2025

Completed
Last Updated

August 24, 2025

Status Verified

April 1, 2025

Enrollment Period

3.5 years

First QC Date

November 5, 2018

Results QC Date

July 21, 2025

Last Update Submit

August 6, 2025

Conditions

Hypertension

Keywords

Angiotensin IIAngiotensin Converting Enzyme InhibitorsAngiotensin Receptor BlockersAnesthesia-Mediated Hypotension

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (14)

  • Median Serum Level of Bradykinin 1-8

    up to 1 hour

  • Median Serum Level of Bradykinin 1-7

    Up to 1 hour

  • Median Serum Level of Bradykinin 1-5

    Up to 1 hour

  • Median Serum Level of Aldosterone

    Up to 1 hour

  • Median Serum Level of Angiotensin I

    Up to 1 hour

  • +9 more secondary outcomes

Study Arms (3)

Participants on ACE inhibitors

EXPERIMENTAL

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

Drug: Angiotensin II

Participants on ARBs

EXPERIMENTAL

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

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.

Drug: Angiotensin II

Interventions

Angiotensin IIDRUG

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.

Also known as: Ang II, Giapreza
Other Classes of Antihypertensive AgentsParticipants on ACE inhibitorsParticipants on ARBs

Eligibility Criteria

Age40 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (6)

  • 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.

    PMID: 15728043BACKGROUND

  • 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.

    PMID: 21636935BACKGROUND

  • 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.

    PMID: 28528561BACKGROUND

  • 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.

    PMID: 22319643BACKGROUND

  • 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.

    PMID: 25286986BACKGROUND

  • 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.

    PMID: 9416783BACKGROUND

MeSH Terms

Conditions

Hypertension

Interventions

Angiotensin IIGiapreza

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

AngiotensinsPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsNeuropeptidesPeptidesAmino Acids, Peptides, and ProteinsOligopeptidesNerve Tissue ProteinsProteinsAutacoidsInflammation MediatorsBiological Factors

Results Point of Contact

Title
Rohesh J. Fernando, MD
Organization
Atrium Health Wake Forest Baptist
rfernan@wakehealth.edu
336.716.2712

Study Officials

  • Rohesh Fernando, MD

    Wake Forest University Health Sciences

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 5, 2018

First Posted

November 7, 2018

Study Start

October 3, 2019

Primary Completion

March 21, 2023

Study Completion

March 21, 2023

Last Updated

August 24, 2025

Results First Posted

August 24, 2025

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will not share

Locations

US(1)