Real-world and Innovative Multimodal Prediction and Prevention of Postoperative Mortality and Multi-morbidities
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- University of Pittsburgh
- Enrollment
- 1,200
- Locations
- 5
- Primary Endpoint
- Postoperative Delirium (POD)
Study Overview
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:
- Preoperative personalized prehabilitation with proactive cognitive and behavioral interventions will improve postoperative cognitive outcomes, morbidity, and mortality in high-risk elderly surgical patients.
- 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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Masking Description
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.
Eligibility Criteria
- Ages
- 65 Years to — (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Part I Inclusion Criteria:
- •65 years of age and older
- •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
- •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)
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
Arms & Interventions
CPC Preoperative Intervention (Aim 1)
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.
Intervention: Enhanced Social Support (Behavioral)
CPC Preoperative Intervention (Aim 1)
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.
Intervention: Cognitive Training (Behavioral)
CPC Preoperative Intervention (Aim 1)
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.
Intervention: Daily Exercise (Behavioral)
CPC Preoperative Intervention (Aim 1)
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.
Intervention: Intra-operative Standard of Care (Procedure)
Preoperative Standard of Care (Aim 1)
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.
Intervention: Pre-operative Standard of Care (Procedure)
Preoperative Standard of Care (Aim 1)
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.
Intervention: Intra-operative Standard of Care (Procedure)
Proactive Bundled Intraoperative Interventions (Aim 2)
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.
Intervention: Proactive Bundle Interventions (Other)
Proactive Bundled Intraoperative Interventions (Aim 2)
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.
Intervention: Intra-operative Standard of Care (Procedure)
Reactive Intraoperative Standard of Care (Aim 2)
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.
Intervention: Intra-operative Standard of Care (Procedure)
CPC Preoperative Intervention (Aim 1)
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.
Intervention: Meditation (Behavioral)
CPC Preoperative Intervention (Aim 1)
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.
Intervention: Personalized CPC Prehabilitation (Other)
Outcomes
Primary Outcomes
Postoperative Delirium (POD)
Time Frame: At baseline screening, then up to 30 days post-operatively
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.
Secondary Outcomes
- Depression(at discharge and then at post-operative months of 1, 3, 6, and 12.)
- Acute Kidney Injury (AKI)(within 48 hours)
- 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.)
- Acute Kidney Injury (AKI)(During index hospitalization, up to 30 days post-operatively.)
- Major Adverse Limb Events (MALE)(Post-operative months 1, 3, 6, and 12.)
- Postoperative Stroke(Within 30 days post-surgery.)
Investigators
Senthil Sadhasivam
Professor
University of Pittsburgh