Blood PressureNCT04884802
The GUARDIAN Trial
A study testing Tight blood pressure management and Routine blood pressure management in people with Blood Pressure, run by The University of Texas Health Science Center, Houston at 20 sites in 6 countries.
Trial summary
An international randomized trial to test the primary hypothesis that perioperative tight blood pressure management reduces 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… Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Blood Pressure
- What is being tested?
- Tight blood pressure management and Routine blood pressure management
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6,254 participants
- Where
- 20 sitesin 6 countries
- Study dates
- 25 Jul 2021to 25 Apr 2027
- Phase
- Interventional
- 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
20 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
20 sites in 6 countries
China9 sites, 9 recruiting
- Recruiting
Beijing Shijitan Hospital, Capital Medical University
Beijing
Yuefu Wang, MD, wangyuefu@hotmail.com
- Recruiting
Peking Union Medical College Hospital
Beijing
Hazel Pei, MD, hazelbeijing@vip.163.com
- Recruiting
Peking University First Hospital
Beijing
Dong-Xin Wang, MD
- Recruiting
West China University Hospital
Chengdu
Xiao Liang, MD
- Recruiting
Prince of Wales Hospital, Chinese University of Hong Kong, Shatin
Hong Kong
Matthew Chan, MD, mtvchan@cuhk.edu.hk
- Recruiting
Renji Hospital, Shanghai Jiaotong University School of Medicine
Shanghai
Peiying Li Li, MD,Phd, peiyingli.md@gmail.com
- Recruiting
Shanghai Chest Hospital
Shanghai
Jingxiang Wu, MD, +86-18930857186, wjx1132@163.com
Jingxiang Wu, MD
- Recruiting
Shanghai Ninth People's Hospital
Shanghai
Hong Jiang, MD, dr_jianghongshjy@163.com
- Recruiting
The Affiliated Lianyungang Hospital of Xuzhou Medical University
Xuzhou
Xiaobao Zhang, MD, zhangxb@njmu.edu.cn
United States6 sites, 2 recruiting
- Recruiting
MetroHealth Medical Center
Cleveland, Ohio, 44109
Luis Tollinche, MD, ltollinche@metrohealth.org
- Completed
Cleveland Clinic Fairview Hospital
Cleveland, Ohio, 44111
- Completed
Cleveland Clinic Main Campus
Cleveland, Ohio, 44195
- Recruiting
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
Valerie Anderson, BS, 713-500-4383, Valerie.L.Anderson@uth.tmc.edu
- Completed
University of Nebraska Medical Center
Omaha, Nebraska, 68198
- Completed
Wake Forest University
Wake Forest, North Carolina, 27106
Turkey (Türkiye)2 sites, 2 recruiting
- Recruiting
Bakirkoy Dr. Sadi Konuk Research and Training Hospital
Bakırköy
Gokhan Sertcakacilar, MD, gokhansertcakacilar@hotmail.com
- Recruiting
Konya City Hospital
Konya
Yasin Tire, MD, dryasintire@hotmail.com
Italy1 site, 1 recruiting
- Recruiting
IRCCS Regina Elena National Cancer Institute
Rome
Marco Covotta, MD, marco.covotta@ifo.it
Japan1 site, 1 recruiting
- Recruiting
National Defense Medical College
Tokyo
Tetsuya Shimada, MD, tetsuyanooheya@gmail.com
About this study
Official title: Tight Perioperative Blood Pressure Management to Reduce Serious Cardiovascular, Renal, and Cognitive Complications: The GUARDIAN Trial
An international randomized trial to test the primary hypothesis that perioperative tight blood pressure management reduces 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.
The treatments will be: 1) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg (tight pressure management); or, 2) routine intraoperative blood pressure management (routine pressure management).
Read the detailed description
Qualifying patients will be randomized 1:1, with random-sized blocks, stratified by site. The treatments will be: 1) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg (tight pressure management); or, 2) routine intraoperative blood pressure management (routine pressure management).
Tight pressure management: In patients assigned to tight pressure management, angiotensin converting enzyme inhibitors and angiotensin receptor blockers will not be given the morning of surgery. Other chronic antihypertensives will only be given as necessary to treat hypertension. General anesthesia will be induced with propofol or etomidate which will be given in repeated small boluses or target-controlled infusion in an effort to keep mean arterial pressure ≥85 mmHg. Simultaneously, the vasopressor infusion will be adjusted with the same goal. Anesthetic dose, fluid administration, and vasopressor administration will be adjusted with the goal of maintaining the individual designated baseline mean arterial pressure. Invasive or non-invasive advanced hemodynamic monitoring is not required, but should be used when practical. Clinicians should use available information to optimize vascular volume, afterload, and inotropy.
Routine pressure management: In patients assigned to routine pressure management, ACEIs, ARBs, and/or calcium channel blockers can be given the morning of surgery if deemed appropriate by the attending anesthesiologist. General anesthesia will be induced and maintained per routine.
In both groups, other aspects of anesthetic management will be at the discretion of the responsible anesthesiologist, including the types and volumes of various fluids. Volatile or intravenous anesthesia is permitted. There will be no limitation on ancillary vasoactive, chronotropic, and inotropic drugs. Clinicians will be free to use advanced hemodynamic monitoring (e.g., pulse-wave analysis, esophageal Doppler, etc.). Blood products will be given per routine. Similarly, postoperative analgesic management will be per routine and clinician preference. Neuraxial and peripheral nerve blocks are permitted, but epidural catheters should not be activated until surgery is nearly finished.
In all cases, good judgement will predominate.
- Conditions
- Blood Pressure
- Being tested
- Tight blood pressure management, Routine blood pressure management
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tight blood pressure managementProcedure or surgery
Norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg.
Routine blood pressure managementProcedure or surgery
ACEIs, ARBs, and/or calcium channel blockers can be given the morning of surgery if deemed appropriate by the attending anesthesiologist. Intraoperative blood pressure will be managed per clinical routine.
| Study group | Role | What they receive |
|---|---|---|
| Tight blood pressure management | Experimental | In patients assigned to tight blood pressure control, angiotensin converting enzyme inhibitors and angiotensin receptor blockers will not be given the morning of surgery. Other chronic antihypertensives will only be given as necessary to treat hypertension. Norepinephrine or phenylephrine infusion will be infused at a rate sufficient to maintain intraoperative MAP ≥ 85 mmHg. Receives: Procedure: Tight blood pressure management |
| Routine blood pressure management | Other | ACEIs, ARBs, and/or calcium channel blockers can be given the morning of surgery if deemed appropriate by the attending anesthesiologist. Intraoperative blood pressure will be managed per clinical routine. Receives: Procedure: Routine blood pressure management |
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 3-Minute Diagnostic Interview for the Confusion Assessment Method (3D CAM) will be used twice daily to assess for the presence of delirium.
Measured: 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 posted13 May 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Blood PressureStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 6,254 participants (estimated)
Sponsor and investigators
- 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
- NCT04884802
- Sponsor's protocol ID
- HSC-MS-24-1026
- Status last verified
- Jul 2025
- First submitted
- 5 Apr 2021
- Last updated
- 29 Aug 2025
- Results posted
- No
- FDA-regulated drug
- No
- 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.
Publications
Chen NP, Li YW, Cao SJ, Zhang Y, Li CJ, Zhou WJ, Li M, Du YT, Zhang YX, Xing MW, Ma JH, Mu DL, Wang DX. Intraoperative hypotension is associated with decreased long-term survival in older patients after major noncardiac surgery: Secondary analysis of three randomized trials. J Clin Anesth. 2024 Oct;97:111520. doi: 10.1016/j.jclinane.2024.111520. Epub 2024 Jul 1.
PubMed 38954871
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
- ClinicalTrials.gov ID
- NCT04884802
- Acronym / sponsor ID
- HSC-MS-24-1026
- Conditions
- Blood Pressure
- Study type
- Interventional
- Recruitment status
- Recruiting
- 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
- 13 May 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.
An international randomized trial to test the primary hypothesis that perioperative tight blood pressure management reduces 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.
The treatments will be: 1) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg (tight pressure management); or, 2) routine intraoperative blood pressure management (routine pressure management).
Detailed description
Qualifying patients will be randomized 1:1, with random-sized blocks, stratified by site. The treatments will be: 1) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg (tight pressure management); or, 2) routine intraoperative blood pressure management (routine pressure management).
Tight pressure management: In patients assigned to tight pressure management, angiotensin converting enzyme inhibitors and angiotensin receptor blockers will not be given the morning of surgery. Other chronic antihypertensives will only be given as necessary to treat hypertension. General anesthesia will be induced with propofol or etomidate which will be given in repeated small boluses or target-controlled infusion in an effort to keep mean arterial pressure ≥85 mmHg. Simultaneously, the vasopressor infusion will be adjusted with the same goal. Anesthetic dose, fluid administration, and vasopressor administration will be adjusted with the goal of maintaining the individual designated baseline mean arterial pressure. Invasive or non-invasive advanced hemodynamic monitoring is not required, but should be used when practical. Clinicians should use available information to optimize vascular volume, afterload, and inotropy.
Routine pressure management: In patients assigned to routine pressure management, ACEIs, ARBs, and/or calcium channel blockers can be given the morning of surgery if deemed appropriate by the attending anesthesiologist. General anesthesia will be induced and maintained per routine.
In both groups, other aspects of anesthetic management will be at the discretion of the responsible anesthesiologist, including the types and volumes of various fluids. Volatile or intravenous anesthesia is permitted. There will be no limitation on ancillary vasoactive, chronotropic, and inotropic drugs. Clinicians will be free to use advanced hemodynamic monitoring (e.g., pulse-wave analysis, esophageal Doppler, etc.). Blood products will be given per routine. Similarly, postoperative analgesic management will be per routine and clinician preference. Neuraxial and peripheral nerve blocks are permitted, but epidural catheters should not be activated until surgery is nearly finished.
In all cases, good judgement will predominate.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tight blood pressure management | Experimental | Procedure: Tight blood pressure managementIn patients assigned to tight blood pressure control, angiotensin converting enzyme inhibitors and angiotensin receptor blockers will not be given the morning of surgery. Other chronic antihypertensives will only be given as necessary to treat hypertension. Norepinephrine or phenylephrine infusion will be infused at a rate sufficient to maintain intraoperative MAP ≥ 85 mmHg. |
| Routine blood pressure management | Other | Procedure: Routine blood pressure managementACEIs, ARBs, and/or calcium channel blockers can be given the morning of surgery if deemed appropriate by the attending anesthesiologist. Intraoperative blood pressure will be managed per clinical routine. |
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 |
|---|---|---|
| Tight blood pressure managementNorepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg. | Procedure or surgery | Tight blood pressure management |
| Routine blood pressure managementACEIs, ARBs, and/or calcium channel blockers can be given the morning of surgery if deemed appropriate by the attending anesthesiologist. Intraoperative blood pressure will be managed per clinical routine. | Procedure or surgery | Routine blood pressure management |
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: 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.
- Derived from this study: PubMed 38954871Chen NP, Li YW, Cao SJ, Zhang Y, Li CJ, Zhou WJ, Li M, Du YT, Zhang YX, Xing MW, Ma JH, Mu DL, Wang DX. Intraoperative hypotension is associated with decreased long-term survival in older patients after major noncardiac surgery: Secondary analysis of three randomized trials. J Clin Anesth. 2024 Oct;97:111520. doi: 10.1016/j.jclinane.2024.111520. Epub 2024 Jul 1.
- 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
20 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tight blood pressure management and Routine blood pressure management in people with Blood Pressure, run by The University of Texas Health Science Center, Houston at 20 sites in 6 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: looking for participants now, 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 20 sites in China, United States, Turkey (Türkiye), Greece, Italy and 1 more country. 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.
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?
Contact Valerie L. Anderson, BS ((713) 500-4383, Valerie.L.Anderson@uth.tmc.edu), or a site near the patient. 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?
On the ClinicalTrials.gov record for NCT04884802, which also lists 1 linked publication.
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.