DeliriumNCT02587039
An Intervention to Reduce Delirium After Cardiac Surgery
A study testing Remote ischemic pre-conditioning and Delirium Assessment in people with Delirium and Congenital Heart Disease, run by Johns Hopkins University at 1 site in United States.
Trial summary
Patients that have cardiac surgery may suffer from unrecognized cerebral ischemia or loss of blood flow to the brain temporarily during surgery. This temporary loss of blood flow to the brain may result in a condition called delirium. Delirium is a type temporary confusion. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Delirium, Congenital Heart Disease, Coronary Artery Disease
- What is being tested?
- Remote ischemic pre-conditioning and Delirium Assessment
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to Dec 2015
- Phase
- Interventional
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- ≥65 years old
- Undergoing coronary artery bypass and/or valve surgery
Who cannot join
- Mini mental state exam < 23
- Delirium at baseline
- Inability to speak and understand English
- Severe hearing impairment, resulting in inability to converse
- Planned use of intraoperative ketamine
- Inability to place or tolerate upper extremity tourniquet
- Hemoglobinopathy (e.g. sickle cell disease)
Trial locations and contacts
1 site in 1 country.
United States1 site
The Johns Hopkins Hospital
Baltimore, Maryland, 21287
About this study
Patients that have cardiac surgery may suffer from unrecognized cerebral ischemia or loss of blood flow to the brain temporarily during surgery. This temporary loss of blood flow to the brain may result in a condition called delirium. Delirium is a type temporary confusion. There are some strategies that can help reduce cerebral ischemia during cardiac surgery which can help lead to a reduction in the incidence of delirium. The investigator believes that a strategy called remote ischemic preconditioning will help to reduce the incidence of delirium incidence after cardiac surgery.
Remote ischemic preconditioning is a brief exposure to ischemia. This brief exposure to ischemia occurs in an area of the body that is not undergoing a procedure. This brief exposure to ischemia is not long enough to cause any damage to the body and it has been demonstrated to help protect against more severe ischemic injury that may occur later during surgery. In this study the investigator will use remote ischemic preconditioning to see if it can reduce the incidence delirium after cardiac surgery.
Read the detailed description
Delirium is common after cardiac surgery, occurring in 45-55% of patients, and is independently associated with increased postoperative complications, reduced functional capacity, cognitive decline, and increased mortality. Although the pathophysiology of delirium is unclear, a leading hypothesis is that delirium results from unrecognized cerebral ischemia during surgery. In preliminary data from the investigators group, delirium was reduced in patients randomized to optimal blood pressure control during cardiopulmonary bypass, using novel technology that determines an individual patient's lower limit of cerebral autoregulation. Thus, patients undergoing cardiac surgery may suffer from unrecognized cerebral ischemia that contributes to delirium, and strategies to attenuate the effects of cerebral ischemia may reduce the incidence of delirium.
Ischemic preconditioning represents a novel strategy to attenuate the effects of cerebral ischemia during cardiac surgery. Exposure to a brief period of ischemia, below the threshold for tissue injury, has been demonstrated to protect against the harmful effects of a subsequent more severe ischemic insult, in both animal and human studies. The protection provided by ischemic preconditioning may also be effective when the preconditioning is applied to a location remote from the organ of interest (i.e. a limb). Recently, a large randomized trial in patients undergoing cardiac surgery demonstrated a survival benefit among patients randomized to remote ischemic preconditioning vs. placebo. Remote ischemic preconditioning was achieved by simple inflation of a blood pressure cuff to supra-systolic pressures for 5 minutes, repeated for 3 cycles. However, neurological outcomes were not assessed in this trial, although animal models support potential neurological protection following remote ischemic preconditioning.
In this study the investigator will examine whether remote ischemic preconditioning can reduce delirium, functional decline, and biomarkers of cerebral injury after cardiac surgery. The investigator will explore the mechanism of preconditioning by examining proteomic analyses in a subset of patients. These results will provide data to support an NIH trial to examine the protective effects of remote ischemic preconditioning in cardiac surgery, identify potential mechanisms of action and potential targets for therapeutic pharmacologic interventions.
- Being tested
- Remote ischemic pre-conditioning, Delirium Assessment
- Keywords
- delirium, heart, valve, graft, surgery, coronary
- Medical subject headings
- Delirium, Heart Defects, Congenital, Coronary Artery Disease, Heart Valve Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote ischemic pre-conditioningProcedure or surgery
Remote ischemic preconditioning is exposure to a brief period ischemia to an area or limb that is not involved in surgery. This intervention is believed to reduce the incidence of cerebral (brain) ischemia during cardiac surgery.
Delirium AssessmentBehavioural
The Delirium assessment consist of a validated psychiatric screening tool called the Confusion Assessment Method. We will use this tool to determine if patients have any confusion after surgery.
| Study group | Role | What they receive |
|---|---|---|
| Control: Usual care | Placebo comparator | This group will receive usual care and delirium assessments. Receives: Behavioral: Delirium Assessment |
| Treatment: Ischemic Pre-conditioning | Experimental | Remote Ischemic pre-conditioning before cardiac surgery and delirium assessments. Receives: Procedure: Remote ischemic pre-conditioning; Behavioral: Delirium Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incident Delirium
Delirium will be assessed using the Confusion Assessment Method (CAM) on three of the first four postoperative days. The primary outcome will be positive if delirium occurs by CAM criteria at any of these assessments
Measured: First four postoperative days
Secondary outcomes (1)
Levels of novel cerebral injury biomarkers
Biomarkers include inflammatory proteins, and markers of neuronal damage or change in homeostasis, including glial fibrillary acidic protein and neurotrophic factors
Measured: Within 1 hour before the surgical incision, immediately after cardiopulmonary bypass, 2 hours after cardiopulmonary bypass, and 20 hours after skin closure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2015 (estimated)
- Study startJun 2014
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DeliriumStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Charles Brown, MD, Johns Hopkins University
- Investigators
- Charles Brown, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02587039
- Sponsor's protocol ID
- IRB00030360
- Status last verified
- Aug 2016
- First submitted
- 9 Jul 2014
- Last updated
- 11 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Nakano M, Nomura Y, Suffredini G, Bush B, Tian J, Yamaguchi A, Walston J, Hasan R, Mandal K, Schena S, Hogue CW, Brown CH 4th. Functional Outcomes of Frail Patients After Cardiac Surgery: An Observational Study. Anesth Analg. 2020 Jun;130(6):1534-1544. doi: 10.1213/ANE.0000000000004786.
PubMed 32384343Nomura Y, Nakano M, Bush B, Tian J, Yamaguchi A, Walston J, Hasan R, Zehr K, Mandal K, LaFlam A, Neufeld KJ, Kamath V, Hogue CW, Brown CH 4th. Observational Study Examining the Association of Baseline Frailty and Postcardiac Surgery Delirium and Cognitive Change. Anesth Analg. 2019 Aug;129(2):507-514. doi: 10.1213/ANE.0000000000003967.
PubMed 30540612
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Intervention to Reduce Delirium After Cardiac Surgery
- ClinicalTrials.gov ID
- NCT02587039
- Acronym / sponsor ID
- IRB00030360
- Keywords
- delirium, heart, valve, graft, surgery, coronary
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 27 Oct 2015 (estimated)
- 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.
Patients that have cardiac surgery may suffer from unrecognized cerebral ischemia or loss of blood flow to the brain temporarily during surgery. This temporary loss of blood flow to the brain may result in a condition called delirium. Delirium is a type temporary confusion. There are some strategies that can help reduce cerebral ischemia during cardiac surgery which can help lead to a reduction in the incidence of delirium. The investigator believes that a strategy called remote ischemic preconditioning will help to reduce the incidence of delirium incidence after cardiac surgery.
Remote ischemic preconditioning is a brief exposure to ischemia. This brief exposure to ischemia occurs in an area of the body that is not undergoing a procedure. This brief exposure to ischemia is not long enough to cause any damage to the body and it has been demonstrated to help protect against more severe ischemic injury that may occur later during surgery. In this study the investigator will use remote ischemic preconditioning to see if it can reduce the incidence delirium after cardiac surgery.
Detailed description
Delirium is common after cardiac surgery, occurring in 45-55% of patients, and is independently associated with increased postoperative complications, reduced functional capacity, cognitive decline, and increased mortality. Although the pathophysiology of delirium is unclear, a leading hypothesis is that delirium results from unrecognized cerebral ischemia during surgery. In preliminary data from the investigators group, delirium was reduced in patients randomized to optimal blood pressure control during cardiopulmonary bypass, using novel technology that determines an individual patient's lower limit of cerebral autoregulation. Thus, patients undergoing cardiac surgery may suffer from unrecognized cerebral ischemia that contributes to delirium, and strategies to attenuate the effects of cerebral ischemia may reduce the incidence of delirium.
Ischemic preconditioning represents a novel strategy to attenuate the effects of cerebral ischemia during cardiac surgery. Exposure to a brief period of ischemia, below the threshold for tissue injury, has been demonstrated to protect against the harmful effects of a subsequent more severe ischemic insult, in both animal and human studies. The protection provided by ischemic preconditioning may also be effective when the preconditioning is applied to a location remote from the organ of interest (i.e. a limb). Recently, a large randomized trial in patients undergoing cardiac surgery demonstrated a survival benefit among patients randomized to remote ischemic preconditioning vs. placebo. Remote ischemic preconditioning was achieved by simple inflation of a blood pressure cuff to supra-systolic pressures for 5 minutes, repeated for 3 cycles. However, neurological outcomes were not assessed in this trial, although animal models support potential neurological protection following remote ischemic preconditioning.
In this study the investigator will examine whether remote ischemic preconditioning can reduce delirium, functional decline, and biomarkers of cerebral injury after cardiac surgery. The investigator will explore the mechanism of preconditioning by examining proteomic analyses in a subset of patients. These results will provide data to support an NIH trial to examine the protective effects of remote ischemic preconditioning in cardiac surgery, identify potential mechanisms of action and potential targets for therapeutic pharmacologic interventions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control: Usual care | Placebo comparator | Behavioral: Delirium AssessmentThis group will receive usual care and delirium assessments. |
| Treatment: Ischemic Pre-conditioning | Experimental | Procedure: Remote ischemic pre-conditioning, Behavioral: Delirium AssessmentRemote Ischemic pre-conditioning before cardiac surgery and delirium assessments. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- ≥65 years old
- Undergoing coronary artery bypass and/or valve surgery
Key exclusion criteria (7 listed)
- Mini mental state exam < 23
- Delirium at baseline
- Inability to speak and understand English
- Severe hearing impairment, resulting in inability to converse
- Planned use of intraoperative ketamine
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 |
|---|---|---|
| Remote ischemic pre-conditioningRemote ischemic preconditioning is exposure to a brief period ischemia to an area or limb that is not involved in surgery. This intervention is believed to reduce the incidence of cerebral (brain) ischemia during cardiac surgery. | Procedure or surgery | Treatment: Ischemic Pre-conditioning |
| Delirium AssessmentThe Delirium assessment consist of a validated psychiatric screening tool called the Confusion Assessment Method. We will use this tool to determine if patients have any confusion after surgery. | Behavioural | Control: Usual care, Treatment: Ischemic Pre-conditioning |
Primary outcome
Incident Delirium
Time frame: First four postoperative days
Delirium will be assessed using the Confusion Assessment Method (CAM) on three of the first four postoperative days. The primary outcome will be positive if delirium occurs by CAM criteria at any of these assessments
1 secondary outcome
Levels of novel cerebral injury biomarkers
Time frame: Within 1 hour before the surgical incision, immediately after cardiopulmonary bypass, 2 hours after cardiopulmonary bypass, and 20 hours after skin closure
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2016.
- Derived from this study: PubMed 32384343Nakano M, Nomura Y, Suffredini G, Bush B, Tian J, Yamaguchi A, Walston J, Hasan R, Mandal K, Schena S, Hogue CW, Brown CH 4th. Functional Outcomes of Frail Patients After Cardiac Surgery: An Observational Study. Anesth Analg. 2020 Jun;130(6):1534-1544. doi: 10.1213/ANE.0000000000004786.
- Derived from this study: PubMed 30540612Nomura Y, Nakano M, Bush B, Tian J, Yamaguchi A, Walston J, Hasan R, Zehr K, Mandal K, LaFlam A, Neufeld KJ, Kamath V, Hogue CW, Brown CH 4th. Observational Study Examining the Association of Baseline Frailty and Postcardiac Surgery Delirium and Cognitive Change. Anesth Analg. 2019 Aug;129(2):507-514. doi: 10.1213/ANE.0000000000003967.
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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.
Charles Brown, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Remote ischemic pre-conditioning and Delirium Assessment in people with Delirium and Congenital Heart Disease, run by Johns Hopkins 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 7 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: finished, as of the sponsor's last update on 11 Aug 2016. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incident Delirium (time frame: First four postoperative days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02587039, which also lists 2 linked publications.
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 11 Aug 2016.