Prediction and Prevention of Postoperative Mortality and Morbidity

NCT06042413 | Not Yet Recruiting DMC

• 2 other identifiers: STUDY25110125R01AG085115
• Study Type: interventional
• Target: 1,200
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

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

Keywords

MACCE; Cognitive decline; Perioperative brain health; Neurocognitive disorder; Postoperative delirium

Outcome Measures

Primary Outcomes (1)

• Postoperative Delirium (POD)

  Postoperative delirium will be assessed using the Confusion Assessment Method (CAM). Participants will be classified as having delirium or not having delirium based on standard CAM criteria. A positive CAM indicates the presence of delirium.

  At baseline screening, then up to 30 days post-operatively

Secondary Outcomes (8)

• Depression

  at pre-operative baseline screening, and then at post-operative months of 1, 3, 6, and 12.

• Dementia

  Post-operative months 6 and 12.

• Postoperative Cognitive Decline (POCD)

  Post-operative months 1, 3, 6, and 12.

• Postoperative Neurocognitive Disorder (PND)

  Post-operative months 1 and 3.

• 30-day Major Adverse Cardiac and Cerebrovascular Events (MACCE)

  Within 30 days post-surgery.

Study Arms (4)

CPC Preoperative Intervention (Aim 1)

EXPERIMENTAL

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.

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

Preoperative Standard of Care (Aim 1)

ACTIVE COMPARATOR

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.

Procedure: Pre-operative Standard of Care; Procedure: Intra-operative Standard of Care

Proactive Bundled Intraoperative Interventions (Aim 2)

EXPERIMENTAL

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.

Other: Proactive Bundle Interventions; Procedure: Intra-operative Standard of Care

Reactive Intraoperative Standard of Care (Aim 2)

ACTIVE COMPARATOR

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.

Procedure: Intra-operative Standard of Care

Interventions

Pre-operative Standard of Care PROCEDURE

Participants will receive routine preoperative clinical care per institutional standard practice.

Preoperative Standard of Care (Aim 1)

Personalized CPC Prehabilitation OTHER

Patients referred for elective surgery will be scheduled for a preoperative evaluation (3 to 6 weeks prior to surgery) and will receive standardized and personalized assessment and prehabilitation according to UPMC disease specific algorithms

CPC Preoperative Intervention (Aim 1)

Cognitive Training BEHAVIORAL

Participants will be provided with access to the Lumosity (Lumos Labs) software for installation on a home device. They will be trained to navigate the touchscreen tablet and guided through an introductory series of brain exercise games focused on 5 main categories: memory, speed, attention, flexibility, and problem-solving. Patients will be asked to complete a cognitive exercise dosage of a minimum of 20 minutes a day for ≥5 days prior to their date of surgery. Research coordinators and volunteers from UPMC's Hospital Elder Life Program (HELP) will reach out to participants daily for a quick social check-in and to remind them to perform their training. Compliance data will be retrieved from the Lumosity app.

CPC Preoperative Intervention (Aim 1)

Meditation BEHAVIORAL

A single guided meditation session with instructions will be provided using a smart device. The meditation session will last for at least 10 minutes daily starting at least 1-week prior to surgery. If the subject does not own a smart device, one will be provided or meditation will be completed in-person or over the phone.

CPC Preoperative Intervention (Aim 1)

Daily Exercise BEHAVIORAL

Participants in the intervention group will meet with an occupational or physical therapist approximately 1-6 weeks before surgery who will discuss the potential benefits of exercise and give directions for an easy strength training exercise. Participants will then be provided with a video link for a guided exercise and encouraged to walk or perform a seated strength exercise for ≥ 5 minutes each day for at least 1 week before surgery and after surgery. Patient reported frequency, fitness app compliance and exercise duration with REDCap email or mobile link or over telephone will be collected before and after surgery. Patients will be cleared by an occupational or physical therapist to perform the upper-extremity exercises and will confirm the exercises are not contraindicated after surgery. An occupational or physical therapist will see subject again post-surgery to mitigate risk of injury.

CPC Preoperative Intervention (Aim 1)

Enhanced Social Support BEHAVIORAL

Research coordinators and volunteers from the Hospital Elder Life Program (HELP) will contact participants prior to surgery to discuss concerns, provide regular social support, and remind participants to complete assigned cognitive exercises. The role of family members and caregivers in supporting the participant will also be discussed, and their involvement will be encouraged when appropriate. Participants in the CPC preoperative intervention group may receive preoperative interventions to address depressive symptoms as part of CPC-guided prehabilitation, when clinically indicated.

CPC Preoperative Intervention (Aim 1)

Proactive Bundle Interventions OTHER

Participants randomized to the proactive bundled intervention group (Group D) will receive routine intraoperative SSEP and EEG monitoring and proactive optimization of intraoperative physiology, including maintaining mean arterial pressure ≥65 mmHg, adequate oxygenation, opioid sparing analgesia, and avoidance of deep anesthesia and benzodiazepines. If persistent focal changes in SSEP and EEG (i.e., changes in one hemisphere) occur, reactive measures will be implemented to increase cerebral perfusion, including ensuring hematocrit \>30, maintaining anesthetic BIS \>50-60, and initiating stroke management and thrombectomy if clinically indicated

Proactive Bundled Intraoperative Interventions (Aim 2)

Intra-operative Standard of Care PROCEDURE

This includes routine intraoperative SSEP and EEG monitoring. Physician oversight and interpretation of real-time neuromonitoring data will be performed using a combined on-site and remote model at UPMC. In the event that changes in EEG or SSEP are considered significant by the oversight neurophysiologists, the surgical team will be immediately informed so that immediate appropriate action can be taken to reverse the change.

CPC Preoperative Intervention (Aim 1); Preoperative Standard of Care (Aim 1); Proactive Bundled Intraoperative Interventions (Aim 2); Reactive Intraoperative Standard of Care (Aim 2)

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute on Aging (NIA): collaborator

Study Sites (5)

UPMC Montefiore Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Shadyside Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Mercy Hospital

Pittsburgh, Pennsylvania, 15219, United States

Location

UPMC Passavant Hospital

Pittsburgh, Pennsylvania, 15237, United States

Location

MeSH Terms

Conditions

Dementia; Emergence Delirium; Postoperative Cognitive Complications; Cognitive Dysfunction; Neurocognitive Disorders

Interventions

Cognitive Training; Meditation

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Cognition Disorders

Intervention Hierarchy (Ancestors)

Neurological Rehabilitation; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services; Mind-Body Therapies; Complementary Therapies; Spiritual Therapies; Relaxation Therapy; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Senthilkumar Sadhasivam, MD, MPH, MBA

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Amy Monroe, MPH, MBA

  University of Pittsburgh

  STUDY DIRECTOR

Central Study Contacts

Alisha Maslanka, BS, CCRC

CONTACT

4128646779; maslankaaa@upmc.edu

Dayana Alsamsam, BSPS, MSc

CONTACT

412-623-4147; alsamsamd@upmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Participants are not blinded in Aim 1, however in the intraoperative intervention trial (Aim 2), participants and family members are blinded to the intervention assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Up to 1,200 participants aged 65 years and older scheduled for elective cardiac or vascular surgery will be screened. Approximately 1,000 higher-risk participants (≥2.5% predicted risk of 30-day mortality or MACCE) who proceed to surgery will be included in Aim 1. Aim 1 is a pragmatic, non-randomized comparison in which approximately 500 participants receive CPC-guided preoperative prehabilitation and cognitive or behavioral interventions (Group A), and approximately 500 participants receive preoperative standard of care without CPC referral (Group B). Assignment is based on real-world clinical referral practices. Participants from Aim 1 who require intraoperative neurophysiological monitoring will be screened for Aim 2. Eligible participants (approximately 500) will be stratified by Aim 1 group and randomized 1:1 to reactive standard-of-care intraoperative management (Group C, n=250) or proactive bundled intraoperative interventions (Group D, n=250).

Study Record Dates

• First Submitted: September 6, 2023
• First Posted: September 18, 2023
• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)