Clinical trial NCT06952387: PeRsonalized Blood prEssure Management on Postoperative Complications and Mortality in hIgh-risk Patients Undergoing Major Non-cardiac Surgery (PREMIUM)
Official title: Effect of Personalized Blood Pressure Management on Postoperative Complications and Mortality in High-risk Patients Undergoing Major Non-cardiac Surgery: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Hypotension
Keywords: Blood Pressure
Postoperative complications
Mortality
Non-cardiac surgery
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2025-04-30
Enrollment: 1624
Sex: ALL
Minimum age (years): 65
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: High-risk populations, particularly elderly individuals and patients with cardiovascular comorbidities, exhibit markedly elevated incidences of postoperative myocardial injury (MINS), acute kidney injury (AKI), and mortality.

Intraoperative hypotension (IOH), a pervasive clinical phenomenon affecting 40%-90% of surgical cases, Substantial observational evidence links IOH severity/duration to ischemic organ injuries (MINS, AKI) and long-term morbidity.Nevertheless, inherent limitations of observational designs-particularly residual confounding-preclude definitive causal inferences. Notably, randomized controlled trials (RCTs) investigating goal-directed hemodynamic interventions demonstrate inconsistent clinical benefits, underscoring the imperative to clarify causal mechanisms between IOH and organ injury. This causal ambiguity arises from two unresolved scientific questions:

(1) Threshold personalization deficit; (2) Therapeutic strategy limitations. In light of current evidence, perioperative hypotension management demands personalized strategies, the investigators propose a multicenter randomized controlled trial (RCT) that aims to clarify the clinical benefits of individualized blood pressure management.

Detailed description: Anesthesia- and surgery-related complications and mortality constitute a critical global public health burden. Annually, over 300 million surgical procedures are performed worldwide, with postoperative complications and mortality standing as predominant contributors to adverse outcomes. High-risk populations, particularly elderly individuals and patients with cardiovascular comorbidities, exhibit markedly elevated incidences of postoperative myocardial injury (MINS), acute kidney injury (AKI), and mortality. Refinement of perioperative management protocols-especially precision-guided hemodynamic control-has emerged as a pivotal strategy for optimizing patient prognosis.

Intraoperative hypotension (IOH), a pervasive clinical phenomenon affecting 40%-90% of surgical cases, is conventionally defined through either absolute thresholds (e.g., systolic blood pressure (SBP) \<90 mmHg or mean arterial pressure (MAP) \<65 mmHg) or relative reductions from baseline values (\>20% decline). Its high prevalence and association with end-organ hypoperfusion have positioned IOH as a central concern in perioperative care. Substantial observational evidence links IOH severity/duration to ischemic organ injuries (MINS, AKI) and long-term morbidity. Nevertheless, inherent limitations of observational designs-particularly residual confounding-preclude definitive causal inferences. Notably, randomized controlled trials (RCTs) investigating goal-directed hemodynamic interventions demonstrate inconsistent clinical benefits, underscoring the imperative to clarify causal mechanisms between IOH and organ injury.

This causal ambiguity arises from two unresolved scientific questions:

1. Threshold personalization deficit: Current paradigms predominantly apply population-based fixed thresholds (e.g., MAP ≥75-80 mmHg vs. ≥60 mmHg), disregarding interindividual hemodynamic variability. Although The Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) study used personalized blood pressure targets, its approach of measuring baseline blood pressure during a single clinic visit conflicts with current evidence. Research shows that 24-hour ambulatory monitoring is the most reliable method to capture an individual's true baseline blood pressure and daily fluctuations.
2. Therapeutic strategy limitations: Conventional protocols emphasizing aggressive vasopressor use to achieve arbitrary pressure targets may inadvertently increase complications like anastomotic leakage and AKI. Furthermore, the multifactorial etiology of IOH-encompassing hypovolemia, vasoplegia, and impaired cardiac contractility-demands etiology-specific management algorithms rather than universal interventions.

In light of current evidence, perioperative hypotension management demands personalized strategies. To address this need, the investigators propose a multicenter randomized controlled trial (RCT) that pioneers the integration of ambulatory blood pressure monitoring (ABPM) with etiology-specific intervention protocols. This study aims to clarify the clinical benefits of individualized blood pressure management and establish high-quality evidence to advance precision anesthesia practices in perioperative care.

Eligibility criteria: Inclusion Criteria:

* Aged 65-90 yr;
* Scheduled to undergo elective non-cardiac major surgery under general anesthesia (with an estimated surgery duration of ≥ 2 hours and an anticipated postoperative hospital stay of ≥ 2 days);
* Patients with high cardiovascular risk, meeting at least one of the following conditions:

  1. History of stroke;
  2. History of coronary artery disease;
  3. History of congestive heart failure;
  4. History of peripheral arterial disease;
  5. Preoperative brain natriuretic peptide (BNP) ≥ 92 mg/L or N-terminal pro-brain natriuretic peptide (NT-proBNP) ≥ 300 ng/L;
  6. Preoperative cardiac troponin (cTn) or high-sensitivity cardiac troponin (hs-cTn) \> upper reference limit;
  7. Hypertension requiring medication treatment;
  8. Diabetes requiring medication treatment;
  9. History of chronic kidney disease;
  10. Continuous smoking for 2 years or more, with interruptions of less than one month before the current hospital admission;
  11. Hypercholesterolemia;
  12. History of transient ischemic attack.

Exclusion Criteria:

* Refuse to participate this trial;
* Inability to communicate in the preoperative period because of coma, profound dementia, or language barrier;
* Severe uncontrolled hypertension before surgery (systolic blood pressure ≥ 180 mmHg, diastolic blood pressure ≥ 110 mmHg);
* Severe hepatic dysfunction (Child-Pugh Class C); or severe renal dysfunction required preoperative dialysis; or American Society of Anesthesiologists (ASA) physical status ≥ V; or expectation lifespan ≤ 24h;
* Unstable cardiovascular conditions: acute coronary syndrome, decompensated heart failure, severe arrhythmias, severe valvular heart disease;
* Scheduled to undergo neurosurgical procedures, transplantation, vascular surgery;
* Urgent surgery;
* Diagnosed with sepsis or sepsis shock before surgery.
* Requiring vasopressor treatment before surgery.
* Unable to finish 24-hour automated blood pressure monitor;
* Current participation in another interventional study.
* Any condition deemed ineligible for participation by clinicians.

Primary outcomes:
measure: A composite of postoperative complications and mortality within 30 days after surgery
timeFrame: Up to 30 days after surgery
Secondary outcomes:
measure: The individual components of the primary composite outcome within 30 days after surgery
timeFrame: Up to 30 days after surgery
measure: Proportion of ICU admission after surgery
timeFrame: Up to 30 days after surgery
measure: Length of stay in ICU after surgery
timeFrame: Up to 30 days after surgery
measure: Length of stay in the hospital after surgery
timeFrame: Up to 30 days after surgery
measure: Other major postoperative complications within 30 days after surgery
timeFrame: Up to 30 days after surgery
measure: Time to first oral intake after surgery
timeFrame: Up to 30 days after surgery
measure: Time to first flatus passage after surgery
timeFrame: Up to 30 days after surgery
Other outcomes:
measure: Overall survival after surgery
timeFrame: Up to 1 year after surgery
measure: Disability at 6 months after surgery
timeFrame: At 6 months after surgery
measure: Disability at 1 year after surgery
timeFrame: At 1 year after surgery
measure: Quality of life at 6 months after surgery
timeFrame: At 6 months after surgery
measure: Quality of life at 1 year after surgery
timeFrame: At 1 year after surgery
Locations:
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The Affiliated Panyu Central Hospital of Guangzhou Medical University
state: Guangdong
city: Shenzhen
country: China
facility: The Third People's Hospital of Shenzhen
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital
state: Zhejiang
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Ke-Xuan Liu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wesselink EM, Kappen TH, Torn HM, Slooter AJC, van Klei WA. Intraoperative hypotension and the risk of postoperative adverse outcomes: a systematic review. Br J Anaesth. 2018 Oct;121(4):706-721. doi: 10.1016/j.bja.2018.04.036. Epub 2018 Jun 20.
citation: Saugel B, Fletcher N, Gan TJ, Grocott MPW, Myles PS, Sessler DI; PeriOperative Quality Initiative XI (POQI XI) Workgroup Members. PeriOperative Quality Initiative (POQI) international consensus statement on perioperative arterial pressure management. Br J Anaesth. 2024 Aug;133(2):264-276. doi: 10.1016/j.bja.2024.04.046. Epub 2024 Jun 4.
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citation: Marcucci M, Painter TW, Conen D, Lomivorotov V, Sessler DI, Chan MTV, Borges FK, Leslie K, Duceppe E, Martinez-Zapata MJ, Wang CY, Xavier D, Ofori SN, Wang MK, Efremov S, Landoni G, Kleinlugtenbelt YV, Szczeklik W, Schmartz D, Garg AX, Short TG, Wittmann M, Meyhoff CS, Amir M, Torres D, Patel A, Ruetzler K, Parlow JL, Tandon V, Fleischmann E, Polanczyk CA, Lamy A, Jayaram R, Astrakov SV, Wu WKK, Cheong CC, Ayad S, Kirov M, de Nadal M, Likhvantsev VV, Paniagua P, Aguado HJ, Maheshwari K, Whitlock RP, McGillion MH, Vincent J, Copland I, Balasubramanian K, Biccard BM, Srinathan S, Ismoilov S, Pettit S, Stillo D, Kurz A, Belley-Cote EP, Spence J, McIntyre WF, Bangdiwala SI, Guyatt G, Yusuf S, Devereaux PJ; POISE-3 Trial Investigators and Study Groups. Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial. Ann Intern Med. 2023 May;176(5):605-614. doi: 10.7326/M22-3157. Epub 2023 Apr 25.
citation: Futier E, Lefrant JY, Guinot PG, Godet T, Lorne E, Cuvillon P, Bertran S, Leone M, Pastene B, Piriou V, Molliex S, Albanese J, Julia JM, Tavernier B, Imhoff E, Bazin JE, Constantin JM, Pereira B, Jaber S; INPRESS Study Group. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1346-1357. doi: 10.1001/jama.2017.14172.
citation: Nicklas JY, Bergholz A, Dake F, Pham HHD, Rabe MC, Schlichting H, Skrovanek S, Flick M, Kouz K, Fischer M, Olotu C, Izbicki JR, Mann O, Fisch M, Schmalfeldt B, Frosch KH, Renne T, Krause L, Zollner C, Saugel B. Personalised blood pressure management during major noncardiac surgery and postoperative neurocognitive disorders: a randomised trial. BJA Open. 2024 Jul 1;11:100294. doi: 10.1016/j.bjao.2024.100294. eCollection 2024 Sep.
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