Major SurgeryPhase 4NCT04934683
The GUARDIAN Trial - Induction Agent Sub-Study
A Phase 4 study testing Routine Blood Pressure Management, Tight Blood Pressure Management and Etomidate Induction in people with Major Surgery, run by The University of Texas Health Science Center, Houston at 11 sites in 4 countries.
Trial summary
This is a sub-study of the overall GUARDIAN trial (NCT04884802) in which some GUARDIAN trial participants will be additionally randomized to etomidate vs propofol for anesthetic induction. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Major Surgery
- What is being tested?
- Routine Blood Pressure Management, Tight Blood Pressure Management and Etomidate Induction
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6,254 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 25 Jul 2021to 25 Apr 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 45 years old;
- Scheduled for major noncardiac surgery expected to last at least 2 hours;
- Having general anesthesia, neuraxial anesthesia, or the combination;
- Expected to require at least overnight hospitalization (planned ICU admission is acceptable);
- Are designated ASA physical status 2-4 (ranging from mild systemic disease through severe systemic disease that is a constant threat to life);
- Expected to have direct intraoperative blood pressure monitoring with an arterial catheter;
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- Cared for by clinicians willing to follow the GUARDIAN protocol;
- Subject to at least one of the following risk factors:
- Age >65 years;
- History of peripheral arterial disease;
- History of coronary artery disease;
- History of stroke or transient ischemic attack;
- Serum creatinine >175 μmol/L (>2.0 mg/dl) within 6 months;
- Diabetes requiring medication;
- Current smoking or 15 pack-year history of smoking tobacco;
- Scheduled for major vascular surgery;
- Body mass index ≥35 kg/m2;
- Preoperative high-sensitivity troponin T >14 ng/L or troponin I equivalent, defined as ≥15 ng/L (Abbott assay), 19 ng/L (Siemens assay, [Borges, unpublished]), or 25% of the 99% percentile for other assays - all within 6 months;
- B-type natriuretic protein (BNP) >80 ng/L or N-terminal B-type natriuretic protein (NTProBNP) >200 ng/L within six months.
Who cannot join
- Are scheduled for carotid artery surgery;
- Are scheduled for intracranial surgery;
- Are scheduled for partial or complete nephrectomy;
- Are scheduled for pheochromocytoma surgery;
- Are scheduled for liver or kidney transplantation;
- Require preoperative intravenous vasoactive medications;
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- Have a condition that precludes routine or tight blood pressure management such as surgeon request for relative hypotension;
- Require beach-chair positioning;
- Have a documented history of dementia;
- Have language, vision, or hearing impairments that may compromise cognitive assessments;
- Have contraindications to norepinephrine or phenylephrine per clinician judgement;
- Have previously participated in the GUARDIAN trial.
Trial locations and contacts
11 sites in 4 countries. Contact the study team or a site near you to ask about taking part.
11 sites in 4 countries
China5 sites
Beijing Shijitan Hospital, Capital Medical University
Beijing
Peking Union Medical College Hospital
Beijing
Shanghai Ninth People's Hospital
Shanghai, Shanghai Municipality, 200025
Shanghai Chest Hospital
Shanghai
West China Hospital
Sichuan
United States4 sites
MetroHealth Medical Center
Cleveland, Ohio, 44109
Cleveland Clinic Fairview Hospital
Cleveland, Ohio, 44111
Cleveland Clinic Main Campus
Cleveland, Ohio, 44195
University of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
Official title: Tight Perioperative Blood Pressure Management to Reduce Serious Cardiovascular, Renal, and Cognitive Complications: The GUARDIAN Trial (Induction Agent Sub-Study Comparing Etomidate and Propofol)
This is a sub-study of the overall GUARDIAN trial (NCT04884802) in which some GUARDIAN trial participants will be additionally randomized to etomidate vs propofol for anesthetic induction.
Read the detailed description
Participants in the underlying GUARDIAN trial (NCT04884802) will be randomized to: 1) routine intraoperative blood pressure management (routine pressure management); or 2) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg (tight pressure management). Participants in this sub-study will be additionally randomized to etomidate or propofol for induction of anesthesia.
- Conditions
- Major Surgery
- Being tested
- Routine Blood Pressure Management, Tight Blood Pressure Management, Etomidate Induction, Propofol Induction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Routine Blood Pressure ManagementProcedure or surgery
Routine blood pressure control.
Tight Blood Pressure ManagementProcedure or surgery
Tight blood pressure control.
Etomidate InductionDrug
Anesthetic induction with etomidate.
Propofol InductionDrug
Anesthetic induction with propofol.
| Study group | Role | What they receive |
|---|---|---|
| Routine Blood Pressure Management and Etomidate Induction | Active comparator | Etomidate will be used as the anesthetic induction agent. Receives: Procedure: Routine Blood Pressure Management; Drug: Etomidate Induction |
| Routine Blood Pressure Management and Propofol Induction | Active comparator | Propofol will be used as the anesthetic induction agent. Receives: Procedure: Routine Blood Pressure Management; Drug: Propofol Induction |
| Tight Blood Pressure Management and Etomidate Induction | Active comparator | Etomidate will be used as the anesthetic induction agent. Receives: Procedure: Tight Blood Pressure Management; Drug: Etomidate Induction |
| Tight Blood Pressure Management and Propofol Induction | Active comparator | Propofol will be used as the anesthetic induction agent. Receives: Procedure: Tight Blood Pressure Management; Drug: Propofol Induction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with a Composite of Major Perfusion-Related Complications
The primary outcome is a composite of major perfusion-related complications (myocardial injury, stroke, non-fatal cardiac arrest, Stage 2-3 acute kidney injury, deep or organ-space infection, sepsis, and death) in the 30 days after major non-cardiac surgery.
Measured: During the initial 30 days after major non-cardiac surgery
Secondary outcomes (1)
Number of Participants with Postoperative Delirium
The Postoperative Delirium Three-dimensional Confusion Assessment Method (3D CAM) will be used to assess for the presence of delirium over the initial four postoperative days.
Measured: During the initial 4 postoperative days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2021
- Study start25 Jul 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion25 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major SurgeryStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 6,254 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Texas Health Science Center, Houston
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Sessler, The University of Texas Health Science Center, Houston
- Investigators
- Daniel I Sessler, MD, Principal investigator, The University of Texas Health Science Center, Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04934683
- Sponsor's protocol ID
- HSC-MS-24-1026 (induction)
- Status last verified
- Jul 2025
- First submitted
- 15 Jun 2021
- Last updated
- 29 Aug 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Each center will retain ownership of its own data. Publication of center-specific data will not be allowed until after the Main Trial Report is published, or two years have elapsed since enrollment of the last patient. The Executive Committee welcomes suggestions for sub-studies based on a partial or the full trial dataset. Sub-studies will be allocated based on importance and novelty of the proposals, and priority will be given to high-enrolling centers. However, all multi-center publications will be on a collaborative basis and include appropriate co-authors. The Executive Committee will do its best to be fair and equitable in assigning sub-studies. Data will be shared with external parties on a collaborative basis with approval of the Executive Committee and appropriate data-use agreements.
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tight Perioperative Blood Pressure Management to Reduce Serious Cardiovascular, Renal, and Cognitive Complications: The GUARDIAN Trial (Induction Agent Sub-Study Comparing Etomidate and Propofol)
- ClinicalTrials.gov ID
- NCT04934683
- Acronym / sponsor ID
- HSC-MS-24-1026 (induction)
- Conditions
- Major Surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 6,254 participants (estimated)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Study start
- 25 Jul 2021 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 25 Apr 2027 (estimated)
- First posted
- 22 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a sub-study of the overall GUARDIAN trial (NCT04884802) in which some GUARDIAN trial participants will be additionally randomized to etomidate vs propofol for anesthetic induction.
Detailed description
Participants in the underlying GUARDIAN trial (NCT04884802) will be randomized to: 1) routine intraoperative blood pressure management (routine pressure management); or 2) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg (tight pressure management). Participants in this sub-study will be additionally randomized to etomidate or propofol for induction of anesthesia.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Routine Blood Pressure Management and Etomidate Induction | Active comparator | Procedure: Routine Blood Pressure Management, Drug: Etomidate InductionEtomidate will be used as the anesthetic induction agent. |
| Routine Blood Pressure Management and Propofol Induction | Active comparator | Procedure: Routine Blood Pressure Management, Drug: Propofol InductionPropofol will be used as the anesthetic induction agent. |
| Tight Blood Pressure Management and Etomidate Induction | Active comparator | Procedure: Tight Blood Pressure Management, Drug: Etomidate InductionEtomidate will be used as the anesthetic induction agent. |
| Tight Blood Pressure Management and Propofol Induction | Active comparator | Procedure: Tight Blood Pressure Management, Drug: Propofol InductionPropofol will be used as the anesthetic induction agent. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- At least 45 years old;
- Scheduled for major noncardiac surgery expected to last at least 2 hours;
- Having general anesthesia, neuraxial anesthesia, or the combination;
- Expected to require at least overnight hospitalization (planned ICU admission is acceptable);
- Are designated ASA physical status 2-4 (ranging from mild systemic disease through severe systemic disease that is a constant threat to life);
Key exclusion criteria (12 listed)
- Are scheduled for carotid artery surgery;
- Are scheduled for intracranial surgery;
- Are scheduled for partial or complete nephrectomy;
- Are scheduled for pheochromocytoma surgery;
- Are scheduled for liver or kidney transplantation;
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 |
|---|---|---|
| Routine Blood Pressure ManagementRoutine blood pressure control. | Procedure or surgery | Routine Blood Pressure Management and Etomidate Induction, Routine Blood Pressure Management and Propofol Induction |
| Tight Blood Pressure ManagementTight blood pressure control. | Procedure or surgery | Tight Blood Pressure Management and Etomidate Induction, Tight Blood Pressure Management and Propofol Induction |
| Etomidate InductionAnesthetic induction with etomidate. | Drug | Routine Blood Pressure Management and Etomidate Induction, Tight Blood Pressure Management and Etomidate Induction |
| Propofol InductionAnesthetic induction with propofol. | Drug | Routine Blood Pressure Management and Propofol Induction, Tight Blood Pressure Management and Propofol Induction |
Primary outcome
Number of Participants with a Composite of Major Perfusion-Related Complications
Time frame: During the initial 30 days after major non-cardiac surgery
The primary outcome is a composite of major perfusion-related complications (myocardial injury, stroke, non-fatal cardiac arrest, Stage 2-3 acute kidney injury, deep or organ-space infection, sepsis, and death) in the 30 days after major non-cardiac surgery.
1 secondary outcome
Number of Participants with Postoperative Delirium
Time frame: During the initial 4 postoperative days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2025.
- Individual participant dataSharing planned: Yes. Each center will retain ownership of its own data. Publication of center-specific data will not be allowed until after the Main Trial Report is published, or two years have elapsed since enrollment of the last patient. The Executive Committee welcomes suggestions for sub-studies based on a partial or the full trial dataset. Sub-studies will be allocated based on importance and novelty of the proposals, and priority will be given to high-enrolling centers. However, all multi-center publications will be on a collaborative basis and include appropriate co-authors. The Executive Committee will do its best to be fair and equitable in assigning sub-studies. Data will be shared with external parties on a collaborative basis with approval of the Executive Committee and appropriate data-use agreements.
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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.
Daniel I Sessler, MD principal investigator
The University of Texas Health Science Center, Houston
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Routine Blood Pressure Management, Tight Blood Pressure Management and Etomidate Induction in people with Major Surgery, run by The University of Texas Health Science Center, Houston at 11 sites in 4 countries.
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 19 inclusion and 12 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: enrolling by invitation, as of the sponsor's last update on 29 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 11 sites in China, United States, Greece, Japan. 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?
This study is still under way. Results are not available in the source record yet.
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?
Number of Participants with a Composite of Major Perfusion-Related Complications (time frame: During the initial 30 days after major non-cardiac surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Aug 2025.