Interventions for Silent Brain Infarction and Perioperative Neurocognitive Disorders in Cardiovascular Surgery

NCT07048002 | Recruiting DMC

• 1 other identifier: The INSPIRE study
• Study Type: interventional
• Target: 912
• Locations: 1 country
• Sites: 5

Brief Summary

the purpose of the study is to investigate whether a combined anesthetic targets bundle, known as the NeuroFirst strategy, focused on neurological protection, can reduce the incidence of silent brain infarction (SBI) and perioperative neurocognitive disorders (PND) in patients undergoing cardiac surgery. Additionally, the trial will assess the safety of this strategy. The NeuroFirst target bundle incorporates multiple parameters, including mean arterial pressure (MAP), bispectral index (BIS), regional cerebral oxygen saturation (rSO2), and arterial inflow temperature during cardiopulmonary bypass. The primary question this study seeks to answer is: Does the NeuroFirst strategy reduce the incidence of SBI and PND in cardiac surgery? To address this, researchers will compare the NeuroFirst strategy with routine institutional practices based on published guidelines. Participants will be randomly assigned to either the NeuroFirst group or the routine care group. All participants will undergo magnetic resonance imaging (MRI), be assessed using the Confusion Assessment Method (CAM) and the Montreal Cognitive Assessment (MoCA), and be followed for up to one year postoperatively.

Conditions

Silent Brain Infarction; Neurocognitive Disorders; Cardiac Surgery; Neuroprotective

Outcome Measures

Primary Outcomes (1)

• the 7-day incidence of new-onset silent brain infarction (SBI)

  New-onset silent brain infarction refers to newly developed cerebral infarctions detected on MRI, compared with the preoperative MRI, in the absence of any corresponding clinical symptoms of cerebral infarction.

  within 7 days postoperatively

Secondary Outcomes (9)

• Key Secondary Outcome: the 30-day incidence of perioperative neurocognitive disorders (PND)

  within 30 days postoperatively

• the 5-day incidence of postoperative delirium

  within five days postoperatively

• the 30-day incidence of new-onset overt stroke

  within 30 days postoperatively

• the 1-year incidence of new-onset overt stroke

  within 1 year postoperatively

• the 1-year incidence of perioperative neurocognitive disorders (PND)

  within 1 year postoperatively

Other Outcomes (3)

• Length of stay (LOS) in intensive care unit (ICU)

  Perioperative

• Length of stay (LOS) in hospital

  Perioperative

• Hospitalization cost

  Perioperative

Study Arms (2)

NeuroFirst target bundle

EXPERIMENTAL

Management for NeuroFirst target bundle

Other: Managements for NeuroFirst target bundle

Routine Management

ACTIVE COMPARATOR

Management for institutional routine in accordance with published guidelines

Other: Managements for institutional routine

Interventions

Managements for NeuroFirst target bundle OTHER

In the intervention group, patient management aims to achieve the NeuroFirst target bundle, including 1) mean arterial pressure (MAP) 65-90 mmHg, 2) bispectral index (BIS) 40-60, 3) regional cerebral oxygen saturation (rSO2)≥ 60% , and 4) arterial inflow temperature \<37 ℃ and rewarming rate \< 0.5 ℃/min after exceeding 30℃ during CPB. To achieve this target bundle, pharmacologic agents, fluid resuscitation, blood transfusion, and other therapeutic modalities will be utilized. These interventions are guided by comprehensive intraoperative monitoring, including conventional hemodynamic monitoring, invasive or non-invasive cardiac output and vascular resistance assessments.

NeuroFirst target bundle

Managements for institutional routine OTHER

MAP, BIS, cerebral rSO2 and arterial inflow temperature during CPB rewarming, will be managed according to institutional routine in accordance with published guidelines.

Routine Management

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female adult patients aged 60 years or older
• Receiving elective cardiovascular surgery with cardiopulmonary bypass
• Written Informed consent provided

You may not qualify if:

• Contraindication to MRI scanning
• Not suitable for receiving interventions to achieve NeuroFirst target bundle
• Unable to receive neuro-cognitive evaluation due to language, vision, or hearing impairments
• Breastfeeding or pregnancy
• Terminal illness with a life expectancy of less than 3 months
• Mental or legal disability
• current enrollment in other interventional study

Sponsors & Collaborators

• Chinese Academy of Medical Sciences, Fuwai Hospital: lead

Study Sites (5)

Beijing Chaoyang Hospital，Capital Medical University

Beijing, Beijing Municipality, 100020, China

RECRUITING

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College

Beijing, Beijing Municipality, 100037, China

RECRUITING

Xuanwu Hospital,Capital Medical University

Beijing, Beijing Municipality, 100053, China

RECRUITING

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100160, China

RECRUITING

The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430014, China

RECRUITING

Related Publications (11)

• Uysal S, Lin HM, Trinh M, Park CH, Reich DL. Optimizing cerebral oxygenation in cardiac surgery: A randomized controlled trial examining neurocognitive and perioperative outcomes. J Thorac Cardiovasc Surg. 2020 Mar;159(3):943-953.e3. doi: 10.1016/j.jtcvs.2019.03.036. Epub 2019 Mar 29.

  PMID: 31056357 BACKGROUND

• Maheshwari A, McCormick PJ, Sessler DI, Reich DL, You J, Mascha EJ, Castillo JG, Levin MA, Duncan AE. Prolonged concurrent hypotension and low bispectral index ('double low') are associated with mortality, serious complications, and prolonged hospitalization after cardiac surgery. Br J Anaesth. 2017 Jul 1;119(1):40-49. doi: 10.1093/bja/aex095.

  PMID: 28974062 BACKGROUND

• Descamps R, Amour J, Besnier E, Bougle A, Charbonneau H, Charvin M, Cholley B, Desebbe O, Fellahi JL, Frasca D, Labaste F, Lena D, Mahjoub Y, Mertes PM, Molliex S, Moury PH, Moussa MD, Oilleau JF, Ouattara A, Provenchere S, Rozec B, Parienti JJ, Fischer MO; OPTIPAM investigators. Perioperative individualized hemodynamic optimization according to baseline mean arterial pressure in cardiac surgery patients: Rationale and design of the OPTIPAM randomized trial. Am Heart J. 2023 Jul;261:10-20. doi: 10.1016/j.ahj.2023.03.005. Epub 2023 Mar 18.

  PMID: 36934980 BACKGROUND

• Gerstenecker A, Norling AM, Jacob A, Lazar RM. Silent Brain Infarction, Delirium, and Cognition in Three Invasive Cardiovascular Procedures: a Systematic Review. Neuropsychol Rev. 2023 Jun;33(2):474-491. doi: 10.1007/s11065-022-09548-1. Epub 2022 Jul 8.

  PMID: 35804216 BACKGROUND

• Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Mark DB, Reves JG, Blumenthal JA; Neurological Outcome Research Group and the Cardiothoracic Anesthesiology Research Endeavors Investigators. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med. 2001 Feb 8;344(6):395-402. doi: 10.1056/NEJM200102083440601.

  PMID: 11172175 BACKGROUND

• Brown CH 4th, Probert J, Healy R, Parish M, Nomura Y, Yamaguchi A, Tian J, Zehr K, Mandal K, Kamath V, Neufeld KJ, Hogue CW. Cognitive Decline after Delirium in Patients Undergoing Cardiac Surgery. Anesthesiology. 2018 Sep;129(3):406-416. doi: 10.1097/ALN.0000000000002253.

  PMID: 29771710 BACKGROUND

• Cheng C, Wan H, Cong P, Huang X, Wu T, He M, Zhang Q, Xiong L, Tian L. Targeting neuroinflammation as a preventive and therapeutic approach for perioperative neurocognitive disorders. J Neuroinflammation. 2022 Dec 12;19(1):297. doi: 10.1186/s12974-022-02656-y.

  PMID: 36503642 BACKGROUND

• Indja B, Woldendorp K, Vallely MP, Grieve SM. Silent Brain Infarcts Following Cardiac Procedures: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2019 May 7;8(9):e010920. doi: 10.1161/JAHA.118.010920.

  PMID: 31017035 BACKGROUND

• Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med. 2003 Mar 27;348(13):1215-22. doi: 10.1056/NEJMoa022066.

  PMID: 12660385 BACKGROUND

• Fanning JP, Wong AA, Fraser JF. The epidemiology of silent brain infarction: a systematic review of population-based cohorts. BMC Med. 2014 Jul 9;12:119. doi: 10.1186/s12916-014-0119-0.

  PMID: 25012298 BACKGROUND

• Sultan I, Bianco V, Kilic A, Jovin T, Jadhav A, Jankowitz B, Aranda-Michel E, D'angelo MP, Navid F, Wang Y, Thoma F, Gleason TG. Predictors and Outcomes of Ischemic Stroke After Cardiac Surgery. Ann Thorac Surg. 2020 Aug;110(2):448-456. doi: 10.1016/j.athoracsur.2020.02.025. Epub 2020 Mar 19.

  PMID: 32199830 BACKGROUND

MeSH Terms

Conditions

Neurocognitive Disorders

Condition Hierarchy (Ancestors)

Mental Disorders

Central Study Contacts

Jia Shi, M.D.

CONTACT

+86 10 88322467; shijia@fuwai.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Chair, Department of Anesthesiology

Study Record Dates

• First Submitted: June 12, 2025
• First Posted: July 2, 2025
• Study Start: July 6, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2028
• Last Updated: November 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)