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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HL130443-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Emory Healthcare | OTHER |
| University of Pennsylvania | OTHER |
| National Institutes of Health (NIH) | NIH |
| Baylor Scott and White Health |
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In this study the investigator will randomize 273 subjects to deep (<20°C), low (20.1°C-24°C), or moderate (24.1°C-28°C) hypothermia during aortic arch surgery with circulatory arrest. The primary purpose of this study is to determine the effect of deep vs low vs moderate hypothermia on neurocognitive function, brain functional connectivity, and leukocyte SUMOylation patterns after surgical circulatory arrest in participants.
Purpose of the Study: Determine the effect of deep vs low vs moderate hypothermia on neurocognitive function, brain functional connectivity, and leukocyte SUMOylation patterns after surgical circulatory arrest.
Hypothesis: Deep hypothermia is superior to moderate hypothermia in reducing postoperative cognitive decline and preserving brain functional connectivity and that low hypothermia is non-inferior to deep hypothermia.
Design and Procedures: 273 informed and consenting patients who are scheduled for elective proximal aortic reconstructive surgery (ascending aorta + aortic valve or root) with concomitant proximal hemi- or total arch replacement via median sternotomy will be randomized to deep (<20°C), low (20.1°C-24°C), or moderate (24.1°C-28°C) hypothermia during circulatory arrest. Cognitive testing using a standard battery will occur preoperatively (baseline), at 4 weeks, and at 1 year after surgery. Neuroimaging procedures before surgery, and at 4 weeks and 1 year after surgery will consist of high-resolution anatomic, resting-state fMRI (rs-fMRI) and magnetic resonance spectroscopy (MRS) sequences. To characterize leukocyte activation, whole blood will be drawn at 5 time points: at baseline (prior to surgery), before circulatory arrest, 10 minutes after reperfusion, 10 minutes after CPB, and 4 hours after CPB.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Deep Hypothermia | Active Comparator | Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature ≤20 degrees Celsius |
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| Low Hypothermia | Active Comparator | Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature 20.1 - 24.0 degrees Celsius |
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| Moderate Hypothermia | Active Comparator | Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature 24.1 - 28 degrees Celsius |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cardiopulmonary bypass machine | Device | Routinely used cardiopulmonary bypass machine (standard of care) will be used to initiate circulatory arrest |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in short-term cognition as measured by continuous cognitive score | To characterize cognitive function over time while minimizing potential redundancy in the cognitive measures, a factor analysis will be performed on the cognitive test scores from baseline. A continuous change score will be calculated by subtracting the baseline cognitive index (the mean of the domain scores from factor analysis) from the follow-up cognitive index at 4 weeks. | From baseline to 4 weeks post-operatively |
| Measure | Description | Time Frame |
|---|---|---|
| Change in SUMO 2/3 levels | Pre-incision, before circulatory arrest, 10 minutes after reperfusion, 10 minutes after cardiopulmonary bypass, 4 hrs after cardiopulmonary bypass | |
| Change in long-term cognition as measured by continuous cognitive score | To characterize cognitive function over time while minimizing potential redundancy in the cognitive measures, a factor analysis will be performed on the cognitive test scores from baseline. A continuous change score will be calculated by subtracting the baseline cognitive index (the mean of the domain scores from factor analysis) from the follow-up cognitive index at 1 year. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joseph P Mathew, MD, MHSc, MBA | Duke Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory Saint Joseph's Hospital | Atlanta | Georgia | 30342 | United States | ||
| Duke University Health System |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38084590 | Derived | Hughes GC, Chen EP, Browndyke JN, Szeto WY, DiMaio JM, Brinkman WT, Gaca JG, Blumenthal JA, Karhausen JA, Bisanar T, James ML, Yanez D, Li YJ, Mathew JP. Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest Trial (GOT ICE): A Randomized Clinical Trial Comparing Outcomes After Aortic Arch Surgery. Circulation. 2024 Feb 27;149(9):658-668. doi: 10.1161/CIRCULATIONAHA.123.067022. Epub 2023 Dec 12. |
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| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D000079690 | Postoperative Cognitive Complications |
| ID | Term |
|---|---|
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
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| OTHER |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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| From baseline to 1 year post-operatively |
| Incidence of delirium | Confusion Assessment Method (CAM) | Up to post-operative day 3 |
| Change in neurological function as measured by NIHSS | Assessed at baseline, post-op day 4, 4 weeks |
| Change in neuronal metabolism | Magnetic resonance spectra (metabolic peaks) of myoinositol, creatine, choline and N-acetyl aspartate | From baseline to 4 weeks |
| Change in resting-state functional connectivity | For the rs-fMRI data, the analyses of primary interest will be the spontaneous, low-frequency fluctuations in the blood oxygen level dependent (BOLD) data of the Default Mode, Salience, and Executive Control Networks. | From baseline to 4 weeks post-operatively |
| Change in Duke Activity Status Index score | From baseline to 4 weeks postoperatively |
| Change in depression score | Measured by the Center for Epidemiological Studies Depression Scale (CES-D). | From baseline to 4 weeks postoperatively |
| Change in anxiety score | Measured by State Trait Anxiety Inventory (STA-I). | From baseline to 4 weeks postoperatively |
| Change in SF-36 score | From baseline to 1 year postoperatively |
| Change in employment status | From baseline to 1 year postoperatively |
| Durham |
| North Carolina |
| 27710 |
| United States |
| Penn Presbyterian Medical Center | Philadelphia | Pennsylvania | 19104 | United States |
| Baylor Scott & White Research Institute | Plano | Texas | 75093 | United States |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D060825 | Cognitive Dysfunction |