Cardiac SurgeryPhase 2NCT03947671
Active Temperature Management After Cardiac Surgery and Its Effect on Postoperative Cognitive Dysfunction
A Phase 2 study testing Rapr Rounds Hyper/Hypothermia Wraps and Acetaminophen in people with Cardiac Surgery and Post-operative Cognitive Dysfunction, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
This study will assess the effect of active postoperative temperature management and its effect on the cognitive function in patients following coronary artery bypass graft (CABG) surgery to determine if active postoperative temperature management to maintain normothermia reduces postoperative cognitive dysfunction… Read more about this study
- Who is it for?
- Ages 20 to 89 years
- Conditions the study is for
- Cardiac Surgery, Post-operative Cognitive Dysfunction, Fever
- What is being tested?
- Rapr Rounds Hyper/Hypothermia Wraps and Acetaminophen
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jan 2020to Oct 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- scheduled coronary artery bypass graft surgery patients, with or without valve surgery
- patients able to give informed consent
Who cannot join
- age < 20 years or > 89 years
- patients with unscheduled CABG +/- valve surgery (i.e. emergency surgery)
- deformity or skin condition of chest or thighs that would interfere with the successful placement of Rapr Round® vest and leg wraps
- patients presenting to the ICU postoperatively with a fever ≥ 38.3
- patients with planned intraoperative circulatory arrest
- prisoners
- pregnant patients
- patients with symptomatic cerebrovascular disease, specifically residual motor deficits, expressive or receptive aphasia from prior stroke or cerebrovascular accident
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
This study will assess the effect of active postoperative temperature management and its effect on the cognitive function in patients following coronary artery bypass graft (CABG) surgery to determine if active postoperative temperature management to maintain normothermia reduces postoperative cognitive dysfunction (POCD) in this population. Additionally, the investigators will explore differences in temperature control variability by using temperature management wraps combined with acetaminophen vs. acetaminophen alone in a pilot arm.
Read the detailed description
As one of the more common hospital-based major interventional procedures, 180,476 CABG surgeries were performed in the United States in 2016, according to the Society of Thoracic Surgeons Adult Cardiac Surgery Database (STS ACSD). Of these, 23,545 operations also involved aortic or mitral valve repair or replacement. The demographic characteristics of patients undergoing cardiac surgery have changed over time, with a higher proportion of elderly patients undergoing increasingly complex procedures. The number of patients with neurological disease prior to surgery has nearly doubled from 1.4% in 2001 to nearly 2.8% as of 2010, and is rising as surgical care improves and includes more such patients .
The recognition of neurological complications associated with cardiac surgery has been report-ed widely, and neurological dysfunction can be categorized as type 1 (brain death, non-fatal stroke, and new transient ischemic attack) or type 2 (delirium and postoperative cognitive dys-function) . The incidence postoperative neurological complications, defined as "permanent stroke" by the STS ACSD, was noted in 2016 to be 1.3% following isolated CABG operations, but was noted to be higher, between 2-3% in CABG patients also receiving aortic or mitral valve surgery as part of their operation. Notably, this statistic does not capture POCD, although steps are being taken to better capture this, perhaps as a patient-reported outcome (PRO) in the future.
As early as 1955, POCD was described by Bedford in the Lancet under the designation "adverse cerebral effects of anesthesia on old people" . It can affect any age group, but does seem to dis-proportionately affect patients age 60 or older, causing difficulty in daily life and their ability to return to work . Short-term POCD, up to 6 weeks postoperatively, occurs in 20-50% of patients undergoing cardiac surgery. Longer-term POCD, defined as a subtle deterioration in cognitive function 6 months following surgery, occurs in 10-30% of cardiac surgery patients . In a longitudinal study with 8.5 years of follow-up, Steinmetz et al. found POCD to be associated with higher mortality (Cox proportional hazard ratio 1.63, 95% confidence interval 1.11-2.38; p = 0.01), earlier retirement, and greater utilization of social financial assistance . Monk et al. found that the risk of death within one year was greater among patients who had POCD when they were discharged from the hospital .
CABG and valve surgery most commonly use the extracorporeal cardiopulmonary bypass machine to perfuse the body during cardiac surgery. The aorta is cross-clamped to allow work and suturing in a near bloodless field. The major blood branches to the brain come off the aorta. When the aorta is cross-clamped, the brain undergoes a period of ischemia. While the patient is on bypass, the body and brain are kept at low temperatures to quell the effects of ischemia. Temperature elevation has been proposed to have an all-or-none response with a defined threshold beyond which the increased temperature aggravates ischemic injury. Hyperthermia leads to physiological and structural changes in the brain which include alterations of enzyme activity and damage to cytoskeletal proteins found in the brain. In addition, hyperthermia causes a release of excitatory neurotransmitters, the production of free radicals, an increase in blood-brain barrier permeability, and increase in intracellular acidosis after ischemic reperfusion all of which have all been proposed as mechanisms through which hyperthermia leads to brain tissue injury and can exacerbate ischemic brain injury .
Intraoperative temperature during cardiac surgery has long been thought to have an association with postoperative neurological outcomes, and has been well studied. In mitigating neuroinflammation and subsequent brain injury, intraoperative hypothermia as compared with normothermia has been the subject of much debate, and outcomes have varied considerably in various studies. The process of rewarming patients as they gradually disengage from cardiopulmonary bypass has been noted as another important process in modulating neuroprotection, and has al-so been studied extensively. Nearly all studies have associated a slower rate of intraoperative rewarming with a decreased incidence of POCD.
Postoperative hyperthermia is a much less well-studied phenomenon. It occurs in approximately 30% of all CABG patients , and one study has associated it with POCD, noting that patients with supra-normal temperatures in the first 24-hour postoperative period following CABG have poorer cognitive outcomes when compared to those with normal temperatures in this setting .
At our institution and many others, the current standard of care pertaining to postoperative hyperthermia management in cardiac surgery patients involves treatment with acetaminophen and room temperature if it rises to greater than or equal to 38.3 degrees.
The Altrix Precision Temperature Management System, and specifically the Rapr Round® product, offers a means by which medical staff may be able to control temperature in cardiac surgery patients postoperatively, while preventing fever from occurring and in per our hypothesis, may be able to decrease short term POCD and its associated sequelae in this patient population. This temperature management system is intended for circulating temperature controlled warm or cold water via patient contact thermal transfer devices for the application of regulating human body temperature in situations where a physician or clinician with prescription privileges determines that temperature therapy is necessary or desirable.
For this study, the Rapr Round® vest and leg wraps are placed around the torso and legs of the patient and adjust body temperature by circulating water through channels in the wrap. In this case the wraps will be used to maintain patient temperature in the intervention group at 36.5 +/- 0.2 degrees Celsius, or normothermia.
- Conditions
- Cardiac Surgery, Post-operative Cognitive Dysfunction, Fever
- Being tested
- Rapr Rounds Hyper/Hypothermia Wraps, Acetaminophen
- Keywords
- temperature regulation
- Medical subject headings
- Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rapr Rounds Hyper/Hypothermia WrapsDevice
Rapr Round® vest and leg wraps will placed around the torso and legs of the participant and will be adjusted to maintain normal body temperature
AcetaminophenDrug
Also called Tylenol
Acetaminophen will be administered as it would be per standard of care
| Study group | Role | What they receive |
|---|---|---|
| Body wrap | Experimental | This group will receive the body wraps post surgery to maintain normothermia. Receives: Device: Rapr Rounds Hyper/Hypothermia Wraps |
| Tylenol | Active comparator | This group will receive the standard of care of monitoring temperature and administering Tylenol if a fever develops. Receives: Drug: Acetaminophen |
| Tylenol with body wrap | Experimental | This group will receive the standard of care of monitoring temperature but will be administered Tylenol and body wraps if a fever develops. Receives: Device: Rapr Rounds Hyper/Hypothermia Wraps; Drug: Acetaminophen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cognitive Function post CABG
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) administered by a clinical psychologist or re-searcher specifically trained by the clinical psychologist. The RBANS is a screening tool that has been standardized to measure the neu-ropsychological status of adult patient between the ages of 20 and 89. It is composed of 12 sub-tests and takes approximately 30 minutes to administer. It is scored using a scaled index score from 40 to 160 with the following score ranges:
130 and above: very superior 120-129: superior 110-119: high average 90-109: average 80-89: low average 70-79: borderline 69 and below: extremely low
Measured: From pre surgery and 6 weeks post surgery
Secondary outcomes (1)
Variability in Temperature
Pattern of body temperature during post-op period measured using electronic thermometers
Measured: Up to 24 hours post surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2019
- Study start22 Jan 2020
- Primary completionOct 2026 (estimated)
- Study completionOct 2026 (estimated)
Why it stopped: Loss of funds
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- Stryker Medical
- Responsible party
- Sponsor
- Investigators
- Vishal Yajnik, MD, MS, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03947671
- Sponsor's protocol ID
- HM20015426
- Status last verified
- Mar 2024
- First submitted
- 25 Apr 2019
- Last updated
- 1 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Active Temperature Management After Cardiac Surgery and Its Effect on Postoperative Cognitive Dysfunction
- ClinicalTrials.gov ID
- NCT03947671
- Acronym / sponsor ID
- HM20015426
- Conditions
- Cardiac Surgery, Post-operative Cognitive Dysfunction, Fever
- Keywords
- temperature regulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Loss of funds
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- Stryker Medical
- Study start
- 22 Jan 2020 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 13 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the effect of active postoperative temperature management and its effect on the cognitive function in patients following coronary artery bypass graft (CABG) surgery to determine if active postoperative temperature management to maintain normothermia reduces postoperative cognitive dysfunction (POCD) in this population. Additionally, the investigators will explore differences in temperature control variability by using temperature management wraps combined with acetaminophen vs. acetaminophen alone in a pilot arm.
Detailed description
As one of the more common hospital-based major interventional procedures, 180,476 CABG surgeries were performed in the United States in 2016, according to the Society of Thoracic Surgeons Adult Cardiac Surgery Database (STS ACSD). Of these, 23,545 operations also involved aortic or mitral valve repair or replacement. The demographic characteristics of patients undergoing cardiac surgery have changed over time, with a higher proportion of elderly patients undergoing increasingly complex procedures. The number of patients with neurological disease prior to surgery has nearly doubled from 1.4% in 2001 to nearly 2.8% as of 2010, and is rising as surgical care improves and includes more such patients .
The recognition of neurological complications associated with cardiac surgery has been report-ed widely, and neurological dysfunction can be categorized as type 1 (brain death, non-fatal stroke, and new transient ischemic attack) or type 2 (delirium and postoperative cognitive dys-function) . The incidence postoperative neurological complications, defined as "permanent stroke" by the STS ACSD, was noted in 2016 to be 1.3% following isolated CABG operations, but was noted to be higher, between 2-3% in CABG patients also receiving aortic or mitral valve surgery as part of their operation. Notably, this statistic does not capture POCD, although steps are being taken to better capture this, perhaps as a patient-reported outcome (PRO) in the future.
As early as 1955, POCD was described by Bedford in the Lancet under the designation "adverse cerebral effects of anesthesia on old people" . It can affect any age group, but does seem to dis-proportionately affect patients age 60 or older, causing difficulty in daily life and their ability to return to work . Short-term POCD, up to 6 weeks postoperatively, occurs in 20-50% of patients undergoing cardiac surgery. Longer-term POCD, defined as a subtle deterioration in cognitive function 6 months following surgery, occurs in 10-30% of cardiac surgery patients . In a longitudinal study with 8.5 years of follow-up, Steinmetz et al. found POCD to be associated with higher mortality (Cox proportional hazard ratio 1.63, 95% confidence interval 1.11-2.38; p = 0.01), earlier retirement, and greater utilization of social financial assistance . Monk et al. found that the risk of death within one year was greater among patients who had POCD when they were discharged from the hospital .
CABG and valve surgery most commonly use the extracorporeal cardiopulmonary bypass machine to perfuse the body during cardiac surgery. The aorta is cross-clamped to allow work and suturing in a near bloodless field. The major blood branches to the brain come off the aorta. When the aorta is cross-clamped, the brain undergoes a period of ischemia. While the patient is on bypass, the body and brain are kept at low temperatures to quell the effects of ischemia. Temperature elevation has been proposed to have an all-or-none response with a defined threshold beyond which the increased temperature aggravates ischemic injury. Hyperthermia leads to physiological and structural changes in the brain which include alterations of enzyme activity and damage to cytoskeletal proteins found in the brain. In addition, hyperthermia causes a release of excitatory neurotransmitters, the production of free radicals, an increase in blood-brain barrier permeability, and increase in intracellular acidosis after ischemic reperfusion all of which have all been proposed as mechanisms through which hyperthermia leads to brain tissue injury and can exacerbate ischemic brain injury .
Intraoperative temperature during cardiac surgery has long been thought to have an association with postoperative neurological outcomes, and has been well studied. In mitigating neuroinflammation and subsequent brain injury, intraoperative hypothermia as compared with normothermia has been the subject of much debate, and outcomes have varied considerably in various studies. The process of rewarming patients as they gradually disengage from cardiopulmonary bypass has been noted as another important process in modulating neuroprotection, and has al-so been studied extensively. Nearly all studies have associated a slower rate of intraoperative rewarming with a decreased incidence of POCD.
Postoperative hyperthermia is a much less well-studied phenomenon. It occurs in approximately 30% of all CABG patients , and one study has associated it with POCD, noting that patients with supra-normal temperatures in the first 24-hour postoperative period following CABG have poorer cognitive outcomes when compared to those with normal temperatures in this setting .
At our institution and many others, the current standard of care pertaining to postoperative hyperthermia management in cardiac surgery patients involves treatment with acetaminophen and room temperature if it rises to greater than or equal to 38.3 degrees.
The Altrix Precision Temperature Management System, and specifically the Rapr Round® product, offers a means by which medical staff may be able to control temperature in cardiac surgery patients postoperatively, while preventing fever from occurring and in per our hypothesis, may be able to decrease short term POCD and its associated sequelae in this patient population. This temperature management system is intended for circulating temperature controlled warm or cold water via patient contact thermal transfer devices for the application of regulating human body temperature in situations where a physician or clinician with prescription privileges determines that temperature therapy is necessary or desirable.
For this study, the Rapr Round® vest and leg wraps are placed around the torso and legs of the patient and adjust body temperature by circulating water through channels in the wrap. In this case the wraps will be used to maintain patient temperature in the intervention group at 36.5 +/- 0.2 degrees Celsius, or normothermia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Body wrap | Experimental | Device: Rapr Rounds Hyper/Hypothermia WrapsThis group will receive the body wraps post surgery to maintain normothermia. |
| Tylenol | Active comparator | Drug: AcetaminophenThis group will receive the standard of care of monitoring temperature and administering Tylenol if a fever develops. |
| Tylenol with body wrap | Experimental | Device: Rapr Rounds Hyper/Hypothermia Wraps, Drug: AcetaminophenThis group will receive the standard of care of monitoring temperature but will be administered Tylenol and body wraps if a fever develops. |
Who may qualify
- Ages
- 20 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- scheduled coronary artery bypass graft surgery patients, with or without valve surgery
- patients able to give informed consent
Key exclusion criteria (8 listed)
- age < 20 years or > 89 years
- patients with unscheduled CABG +/- valve surgery (i.e. emergency surgery)
- deformity or skin condition of chest or thighs that would interfere with the successful placement of Rapr Round® vest and leg wraps
- patients presenting to the ICU postoperatively with a fever ≥ 38.3
- patients with planned intraoperative circulatory arrest
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rapr Rounds Hyper/Hypothermia WrapsRapr Round® vest and leg wraps will placed around the torso and legs of the participant and will be adjusted to maintain normal body temperature | Device | Body wrap, Tylenol with body wrap |
| AcetaminophenAlso: TylenolAcetaminophen will be administered as it would be per standard of care | Drug | Tylenol, Tylenol with body wrap |
Primary outcome
Change in cognitive Function post CABG
Time frame: From pre surgery and 6 weeks post surgery
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) administered by a clinical psychologist or re-searcher specifically trained by the clinical psychologist. The RBANS is a screening tool that has been standardized to measure the neu-ropsychological status of adult patient between the ages of 20 and 89. It is composed of 12 sub-tests and takes approximately 30 minutes to administer. It is scored using a scaled index score from 40 to 160 with the following score ranges: 130 and above: very superior 120-129: superior 110-119: high average 90-109: average 80-89: low average 70-79: borderline 69 and below: extremely low
1 secondary outcome
Variability in Temperature
Time frame: Up to 24 hours post surgery
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vishal Yajnik, MD, MS principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rapr Rounds Hyper/Hypothermia Wraps and Acetaminophen in people with Cardiac Surgery and Post-operative Cognitive Dysfunction, run by Virginia Commonwealth University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cognitive Function post CABG (time frame: From pre surgery and 6 weeks post surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2024; AzTrials last refreshed its copy on 30 Oct 2026.