Clinical trial NCT02433041: Baden Prevention and Reduction of Incidence of Postoperative Delirium Trial
Official title: Baden PRIDe Trial - Baden Prevention and Reduction of Incidence of Postoperative Delirium Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postoperative Delirium
Keywords: Postoperative delirium
Cortisol
NSE
S-100beta
MMSE
Nu-DESC
ICDSC
DOS
Haloperidol
Ketamine
Combination of Haloperidol and Ketamine
Placebo
Prevention of
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Kantonsspital Baden
First posted: 2015-05-04
Enrollment: 200
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to find out whether postoperative delirium can be more properly prevented by the combination of determined preventive agents in past studies. Further on the investigators measure pre- and postoperative cortisol, neuron specific enolase (NSE) and S-100beta levels.

Detailed description: The postoperative delirium remains a challenge for medical stuff concerning detection, therapy and avoidance of consequences. Over the years numerous risk factors were detected which emphasizes the importance of its prevention. Within these studies some possibilities, but no strictly defined rules of action for pharmacological or neuropsychological prevention are described. This is why in this randomized, double-blinded, placebo-controlled study, the investigators want to compare two agents that were found to prevent postoperative delirium to a certain level, even in combination: the investigators arrange the patients within four study groups, one receiving Haloperidol, one Ketamine, one both and one placebo. The patients receive the study drug only once right before induction of anesthesia. After the day of recruitment there is the day of operation and a follow-up of three days (5 days of observation in total, where the investigators will test cognitive function with Mini Mental Status Examination (MMSE), Delirium Observation Scale (DOS), Nursing Delirium Screening Scale (Nu-DESC) or Intensive Care Delirium Screening Checklist (ICDSC). Additionally the investigators will measure and compare pre- and postoperative Cortisol, NSE and S-100beta levels.

Eligibility criteria: Inclusion Criteria:

* Age 65 years and older
* Signed agreement

Exclusion Criteria:

* Delirium at admittance or MMSE score \<24 points
* High risk for postoperative ICU treatment
* Haloperidol or Ketamine intolerance
* Risk of lack of cooperation
* Drug an alcohol abuse
* Dementia
* QT interval (QTc) prolongation (at least 460ms in men, at least 470ms women) or drugs influencing QT interval, such as class Ia and III antiarrhythmics, Gatifloxacin, Moxifloxacin, Pentamidin, Cotrimoxazol, Tacrolimus, Dolasetron
* Parkinson's disease
* Intake of dopaminergic drugs (Levodopa, dopamine agonists)
* Parkinsonism
* Epilepsy
* Unable to be interviewed (severe Dementia, speaking disorders, intubation, respiratory isolation, aphasia, coma, terminal illness)
* Delay of operation of more than 72 hours past hospital admittance
* Body weight \>100kg

Primary outcomes:
measure: Differences among study groups - Significant drop in MMSE of two points in one of the three postoperative follow-up days
timeFrame: 5 day follow-up (preoperative, day of surgery, postoperative days 1-3)
Secondary outcomes:
measure: Quantification of incidence of postoperative delirium based on cognitive testing and lab parameters
timeFrame: 5 day follow-up (preoperative, day of surgery, postoperative days 1-3)
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Alexa Hollinger, MD
role: STUDY_DIRECTOR
References:
citation: Hollinger A, Rust CA, Riegger H, Gysi B, Tran F, Brugger J, Huber J, Toft K, Surbeck M, Schmid HR, Rentsch K, Steiner L, Siegemund M. Ketamine vs. haloperidol for prevention of cognitive dysfunction and postoperative delirium: A phase IV multicentre randomised placebo-controlled double-blind clinical trial. J Clin Anesth. 2021 Feb;68:110099. doi: 10.1016/j.jclinane.2020.110099. Epub 2020 Oct 22.
citation: Riegger H, Hollinger A, Seifert B, Toft K, Blum A, Zehnder T, Siegemund M. Baden Prevention and Reduction of Incidence of Postoperative Delirium Trial (PRIDe): a phase IV multicenter, randomized, placebo-controlled, double-blind clinical trial of ketamine versus haloperidol for prevention of postoperative delirium. Trials. 2018 Feb 26;19(1):142. doi: 10.1186/s13063-018-2498-6.