Postoperative DeliriumPhase 4NCT00561678
Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
A Phase 4 study testing Precedex (Dexmedetomidine) in people with Postoperative Delirium and PD, run by Icahn School of Medicine at Mount Sinai at 10 sites in United States.
Trial summary
Elderly patients who undergo anesthesia and non-cardiac surgery are subject to deterioration of brain function including the development of postoperative delirium (PD) and postoperative cognitive dysfunction (POCD). Read more about this study
- Who is it for?
- Ages 68 years and older
- Conditions the study is for
- Postoperative Delirium, PD, Postoperative Cognitive Dysfunction
- What is being tested?
- Precedex (Dexmedetomidine)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 404 participants
- Where
- 10 sitesUnited States
- Study dates
- Feb 2008to May 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 68 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 68 and older
- elective major surgery under general anesthesia(major surgery is defined by a planned 2 day hospitalization)
- ASA physical status I-III
- capable and willing to consent
- MMSE > 20 (to exclude dementia)
Who cannot join
- Cardiac surgery
- Intracranial Surgery
- Emergency Surgery
- Patients with severe visual or auditory disorder/handicaps
- Illiteracy
- Patients with clinically significant Parkinson's Disease
Show all 14Show fewer
- Patients not expected to be able to complete the 3 and 6 month postoperative tests
- Sick sinus syndrome without pacemaker
- Hypersensitivity to drug or class
- Current 2nd or 3rd degree AV block
- History of clinically significant bradycardia
- Contraindication to the use of an 2A-agonist
- Presence of a major psychiatric condition such as bipolar disorder, major depression, schizophrenia, or dementia
- ASA physical status IV or V
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Cleveland Clinic
Cleveland, Ohio, 44195
University of Maryland
College Park, Maryland, 20742
Ohio State University
Columbus, Ohio, 43210
Englewood Hospital & Medical Center
Englewood, New Jersey, 07631
University of Miami Medical Center
Miami, Florida, 33136
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
The Mayo Clinic
Rochester, Minnesota, 55905
St. Louis University
St Louis, Missouri, 63104
About this study
Elderly patients who undergo anesthesia and non-cardiac surgery are subject to deterioration of brain function including the development of postoperative delirium (PD) and postoperative cognitive dysfunction (POCD). These disorders cause disability, distress for both patients and their families, are associated with other medical complications and account for significant additional health care costs. We currently use relatively primitive approaches to preventing and treating PD and POCD.
Dexmedetomidine is a drug used for sedation in critically ill patients that provides some pain relief and controls the bodies response to stress. The sedation produced by dexmedetomidine appears more similar to natural sleep than any other drug used for anesthesia and postoperative sedation. Data suggesting that dexmedetomidine can prevent delirium following cardiac surgery and the developing understanding of the causes of PD and POCD suggest that dexmedetomidine will be particularly effective.
Read the detailed description
Postoperative Delirium or PD and Postoperative Cognitive Dysfunction or POCD are syndromes of central nervous system dysfunction that significantly complicate the recovery of a proportion of elderly patients following surgery.
Delirium is typically a transient syndrome characterized by a de-novo appearance of several pathognomonic behaviors, including disorientation, decreased attention span, sensory misperceptions, a waxing-and-waning type of confusion, and disorganized thinking. PD typically occurs on postoperative days 1 to 3 and is associated with prolonged hospital stays, increased risks for morbidity and mortality and significant health care expenditures.
The neuroendocrine stress response to surgery, including the immediate postoperative period, remains an important potential etiologic factor. In particular, our data suggests that stress in the immediate postoperative period is poorly controlled by all anesthetic techniques and the normal diurnal variation in cortisol is suppressed in subjects who develop POCD.
Dexmedetomidine is a highly selective alpha 2A agonist currently approved for sedation in the ICU. Dexmedetomidine produces analgesia, sympatholysis, and a light sedation characterized by easy arousal. Its action converges on the endogenous substrates for natural sleep to produce their sedative action, an effect that could prove beneficial to elderly postoperative patients.
We hypothesize that treatment with dexmedetomidine will diminish both PD and POCD. The essential proposition is that modulation of perioperative stress can ameliorate perioperative delirium and cognitive dysfunction.
Based on both the concept of cognitive reserve as well as clinical experience, there is concern that patients with preoperative cognitive impairment are particularly vulnerable to POCD. In general, such patients have been excluded from previous studies. This study is unique in that we will assess all participants for mild cognitive impairment prior to surgery. Assessment of the impact of preexisting cognitive impairment is a secondary aim. A broad goal of this interdisciplinary project is to evaluate POCD, which is primarily an anesthesia concept, in the more general context of dementing illness as explored by geriatric psychiatry.
- Conditions
- Postoperative Delirium, PD, Postoperative Cognitive Dysfunction, POCD
- Being tested
- Precedex (Dexmedetomidine), Placebo
- Keywords
- Postoperative Confusion, Postoperative Delirium, PD, Postoperative Cognitive Dysfunction, POCD
- Medical subject headings
- Emergence Delirium, Postoperative Cognitive Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Precedex (Dexmedetomidine)Drug
Also called Dexmedetomidine
0.5/ug/kg/hr Dexmedetomidine infusions will begin prior to the surgery (no loading dose), and will be maintained at 0.5 mcg/kg/hour throughout surgery and titrated postoperatively for 2 hours postoperatively.
PlaceboDrug
Also called Normal Saline
0.5/ug/kg/hr Placebo infusions will begin prior to the surgery (no loading dose), and will be maintained at 0.5 mcg/kg/hour throughout surgery and titrated postoperatively for 2 hours postoperatively.
| Study group | Role | What they receive |
|---|---|---|
| Precedex | Experimental | Precedex (Dexmedetomidine) Receives: Drug: Precedex (Dexmedetomidine) |
| Placebo | Placebo comparator | Placebo - normal saline Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delirium Battery
Number of Participants with occurrence of Post-Operative Delirium in Post-Anesthesia Care Unit (PACU)
Measured: Day 1
Secondary outcomes (5)
Neuropsychological Testing
Rate of change of cognitive function - data not collected because secondary analysis which was not performed
Measured: at 3 months postoperatively
Intraoperative Bradycardia
Number of participants with intraoperative bradycardia
Measured: day 1
Intraoperative Hypotension
Number of participants with intraoperative hypotension
Measured: day 1
Intraoperative Hypertension
Number of participants with intraoperative hypertension
Measured: day 1
Length of Stay
Length of Stay (LOS) in the hospital
Measured: average 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2007 (estimated)
- Study startFeb 2008
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Postoperative DeliriumStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 404 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Stacie Deiner, Icahn School of Medicine at Mount Sinai
- Investigators
- Jeff Silverstein, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00561678
- Sponsor's protocol ID
- GCO 06-0217
- Other IDs
- 1R01AG029656-01A1
- Status last verified
- Mar 2018
- First submitted
- 19 Nov 2007
- Last updated
- 23 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Deiner S, Luo X, Lin HM, Sessler DI, Saager L, Sieber FE, Lee HB, Sano M; and the Dexlirium Writing Group; Jankowski C, Bergese SD, Candiotti K, Flaherty JH, Arora H, Shander A, Rock P. Intraoperative Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery: A Randomized Clinical Trial. JAMA Surg. 2017 Aug 16;152(8):e171505. doi: 10.1001/jamasurg.2017.1505. Epub 2017 Aug 16.
PubMed 28593326
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
- ClinicalTrials.gov ID
- NCT00561678
- Acronym / sponsor ID
- GCO 06-0217
- Conditions
- Postoperative Delirium, PD, Postoperative Cognitive Dysfunction, POCD
- Keywords
- Postoperative Confusion, Postoperative Delirium, PD, Postoperative Cognitive Dysfunction, POCD
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 404 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Feb 2008
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 21 Nov 2007 (estimated)
- Results
- Posted 29 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Elderly patients who undergo anesthesia and non-cardiac surgery are subject to deterioration of brain function including the development of postoperative delirium (PD) and postoperative cognitive dysfunction (POCD). These disorders cause disability, distress for both patients and their families, are associated with other medical complications and account for significant additional health care costs. We currently use relatively primitive approaches to preventing and treating PD and POCD.
Dexmedetomidine is a drug used for sedation in critically ill patients that provides some pain relief and controls the bodies response to stress. The sedation produced by dexmedetomidine appears more similar to natural sleep than any other drug used for anesthesia and postoperative sedation. Data suggesting that dexmedetomidine can prevent delirium following cardiac surgery and the developing understanding of the causes of PD and POCD suggest that dexmedetomidine will be particularly effective.
Detailed description
Postoperative Delirium or PD and Postoperative Cognitive Dysfunction or POCD are syndromes of central nervous system dysfunction that significantly complicate the recovery of a proportion of elderly patients following surgery.
Delirium is typically a transient syndrome characterized by a de-novo appearance of several pathognomonic behaviors, including disorientation, decreased attention span, sensory misperceptions, a waxing-and-waning type of confusion, and disorganized thinking. PD typically occurs on postoperative days 1 to 3 and is associated with prolonged hospital stays, increased risks for morbidity and mortality and significant health care expenditures.
The neuroendocrine stress response to surgery, including the immediate postoperative period, remains an important potential etiologic factor. In particular, our data suggests that stress in the immediate postoperative period is poorly controlled by all anesthetic techniques and the normal diurnal variation in cortisol is suppressed in subjects who develop POCD.
Dexmedetomidine is a highly selective alpha 2A agonist currently approved for sedation in the ICU. Dexmedetomidine produces analgesia, sympatholysis, and a light sedation characterized by easy arousal. Its action converges on the endogenous substrates for natural sleep to produce their sedative action, an effect that could prove beneficial to elderly postoperative patients.
We hypothesize that treatment with dexmedetomidine will diminish both PD and POCD. The essential proposition is that modulation of perioperative stress can ameliorate perioperative delirium and cognitive dysfunction.
Based on both the concept of cognitive reserve as well as clinical experience, there is concern that patients with preoperative cognitive impairment are particularly vulnerable to POCD. In general, such patients have been excluded from previous studies. This study is unique in that we will assess all participants for mild cognitive impairment prior to surgery. Assessment of the impact of preexisting cognitive impairment is a secondary aim. A broad goal of this interdisciplinary project is to evaluate POCD, which is primarily an anesthesia concept, in the more general context of dementing illness as explored by geriatric psychiatry.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Precedex | Experimental | Drug: Precedex (Dexmedetomidine)Precedex (Dexmedetomidine) |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo - normal saline |
Who may qualify
- Ages
- 68 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (5 listed)
- 68 and older
- elective major surgery under general anesthesia(major surgery is defined by a planned 2 day hospitalization)
- ASA physical status I-III
- capable and willing to consent
- MMSE > 20 (to exclude dementia)
Key exclusion criteria (14 listed)
- Cardiac surgery
- Intracranial Surgery
- Emergency Surgery
- Patients with severe visual or auditory disorder/handicaps
- Illiteracy
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 |
|---|---|---|
| Precedex (Dexmedetomidine)Also: Dexmedetomidine0.5/ug/kg/hr Dexmedetomidine infusions will begin prior to the surgery (no loading dose), and will be maintained at 0.5 mcg/kg/hour throughout surgery and titrated postoperatively for 2 hours postoperatively. | Drug | Precedex |
| PlaceboAlso: Normal Saline0.5/ug/kg/hr Placebo infusions will begin prior to the surgery (no loading dose), and will be maintained at 0.5 mcg/kg/hour throughout surgery and titrated postoperatively for 2 hours postoperatively. | Drug | Placebo |
Primary outcome
Delirium Battery
Time frame: Day 1
Number of Participants with occurrence of Post-Operative Delirium in Post-Anesthesia Care Unit (PACU)
5 secondary outcomes
Neuropsychological Testing
Time frame: at 3 months postoperatively
Intraoperative Bradycardia
Time frame: day 1
Intraoperative Hypotension
Time frame: day 1
Intraoperative Hypertension
Time frame: day 1
Length of Stay
Time frame: average 4 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28593326Deiner S, Luo X, Lin HM, Sessler DI, Saager L, Sieber FE, Lee HB, Sano M; and the Dexlirium Writing Group; Jankowski C, Bergese SD, Candiotti K, Flaherty JH, Arora H, Shander A, Rock P. Intraoperative Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery: A Randomized Clinical Trial. JAMA Surg. 2017 Aug 16;152(8):e171505. doi: 10.1001/jamasurg.2017.1505. Epub 2017 Aug 16.
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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.
Jeff Silverstein, MD principal investigator
Icahn School of Medicine at Mount Sinai
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Precedex (Dexmedetomidine) in people with Postoperative Delirium and PD, run by Icahn School of Medicine at Mount Sinai at 10 sites 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 5 inclusion and 14 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 23 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Delirium Battery (time frame: Day 1). 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 NCT00561678, which also lists 1 linked publication.
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 23 Apr 2018.