Prediction and Prevention of Postoperative Mortality and Morbidity

University of Pittsburgh

Status: Not yet enrolling

Conditions: Perioperative Complications; Postoperative Delirium (POD); Postoperative Neurocognitive Disorder; Postoperative Cognitive Decline; Major Adverse Cardiac and Cerebrovascular Events; Dementia

Treatments: Other: Personalized CPC Prehabilitation; Other: Proactive Bundle Interventions; Behavioral: Meditation; Behavioral: Daily Exercise; Procedure: Pre-operative Standard of Care; Behavioral: Cognitive Training; Behavioral: Enhanced Social Support; Procedure: Intra-operative Standard of Care

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06042413

STUDY25110125

R01AG085115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This study will contribute to creating a prospective and automated preoperative risk assessment algorithm for predicting 30-day mortality, major adverse cardiac and cerebrovascular events (MACCE), and postoperative neurocognitive outcomes following elective cardiac and vascular surgery in older adults. It will evaluate associations between perioperative factors and longer-term neurocognitive outcomes, including postoperative neurocognitive disorder and dementia. In addition, this study will assess scalable, multimodal preoperative and intraoperative interventions to improve perioperative outcomes.

This study will explore two main hypotheses:

1. Preoperative personalized prehabilitation with proactive cognitive and behavioral interventions will improve postoperative cognitive outcomes, morbidity, and mortality in high-risk elderly surgical patients.
2. Proactive bundled intraoperative interventions are superior to reactive standard of care in reducing postoperative cognitive outcomes, MACCE, and mortality.

Expected Outcome: Improved EHR algorithm will have higher predictive accuracy for MACCE and mortality while predicting postoperative cognitive outcomes.

Full description

This study will cover the following two specific aims:

Aim 1. A pragmatic, non-randomized study to assess the effectiveness of preoperative personalized prehabilitation with proactive cognitive and behavioral interventions versus standard of care on reducing postoperative cognitive outcomes (including postoperative delirium within 30 days, postoperative cognitive decline, and dementia), MACCE, and mortality in high-risk surgical elderly patients (≥65 years). Our Electronic Health Record (EHR)-based automated machine-learning risk prediction algorithm for postoperative mortality and MACCE has been developed using >1.25 million surgical patients' data and implemented with superior performance to comparators. This EHR algorithm will identify approximately 1,000 patients at high risk for 30-day mortality and MACCE who proceed to surgery for Aim 1. Participants will receive either standard of care (n=500) or CPC-guided personalized preoperative prehabilitation with proactive cognitive or behavioral interventions (physical exercise, cognitive training, enhanced social support, and depression support) (n=500), based on real-world clinical referral practices rather than randomization. Cognitive assessments will be performed at baseline, discharge, and at 1, 3, 6, and 12 months.

Aim 2 Hypothesis: Proactive bundled intraoperative interventions are superior to standard intraoperative care in reducing postoperative cognitive outcomes, MACCE, and mortality.

Expected Outcome: The refined EHR-based risk prediction algorithm will demonstrate improved accuracy for predicting MACCE, mortality, and postoperative cognitive outcomes.

Enrollment: 1,200 estimated patients

Sex: All

Ages: 65+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Part I Inclusion Criteria:

• 65 years of age and older
• Identified as higher risk (≥2.5%) for 30-day mortality and MACCE based on the UPMC's Perioperative Model (EHR risk prediction algorithm)
• Scheduled for major cardiac surgeries including coronary artery bypass and valvular repair and/or vascular surgeries including carotid endarterectomy, aortic aneurysm repair, and major vascular surgeries
• RAI score ≥ 30
• Informed consent
• English speaking patients

Part II Inclusion Criteria:

• Enrolled in Aim 1 / Part I Preoperative Intervention Trial
• Scheduled for high-risk, cardiac or vascular surgery requiring intraoperative neurophysiological monitoring (IONM)
• Moderate and high risk for mortality based on Society of Thoracic Surgery score (score >4)

Part I Exclusion Criteria:

• Children (<18 years)
• Patients unable to provide consent
• Participants undergoing same day procedures or operations (discharged same day)
• Patients with severe preoperative medical diseases such as blindness or significant visual impairment, unresolved motor weakness, or any other perioperative events or complications that would have a bearing on the patient's ability to perform study tasks, neuropsychological tests, and proposed interventions

Part II Exclusion Criteria:

• Pregnant women
• Patients do not provide consent.
• Patients are unable to participate in cognitive and other behavioral assessment due to physical limitations
• Patients refuse any blood transfusions during surgery

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,200 participants in 4 patient groups

CPC Preoperative Intervention (Aim 1)

Experimental group

Description:

Participants referred to the Center for Perioperative Care (CPC) by their surgical team will receive preoperative prehabilitation and proactive cognitive and behavioral interventions prior to surgery. Assignment to this group is not randomized and reflects real world clinical practice. Participants will receive standard intraoperative monitoring during surgery.

Treatment:

Behavioral: Cognitive Training

Procedure: Intra-operative Standard of Care

Behavioral: Enhanced Social Support

Behavioral: Daily Exercise

Behavioral: Meditation

Other: Personalized CPC Prehabilitation

Preoperative Standard of Care (Aim 1)

Active Comparator group

Description:

Participants who do not receive CPC referral will receive standard preoperative care prior to surgery. Assignment to this group is not randomized. Participants will receive standard intraoperative monitoring during surgery.

Treatment:

Procedure: Intra-operative Standard of Care

Procedure: Pre-operative Standard of Care

Proactive Bundled Intraoperative Interventions (Aim 2)

Experimental group

Description:

Participants in Aim 2 are drawn from Aim 1 participants who meet IONM eligibility. Participants requiring intraoperative neurophysiological monitoring will be randomized on the day of surgery to receive proactive bundled intraoperative interventions in addition to standard intraoperative monitoring.

Treatment:

Other: Proactive Bundle Interventions

Procedure: Intra-operative Standard of Care

Reactive Intraoperative Standard of Care (Aim 2)

Active Comparator group

Description:

Participants in Aim 2 are drawn from Aim 1 participants who meet IONM eligibility. Participants requiring intraoperative neurophysiological monitoring will be randomized on the day of surgery to receive reactive standard of care intraoperative management with routine SSEP and EEG monitoring.

Treatment:

Procedure: Intra-operative Standard of Care