PRIDe: Baden Prevention and Reduction of Incidence of Postoperative Delirium Trial

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Completed

CT.gov ID

NCT02433041

Collaborator

Kantonsspital Baden (Other)

200

Enrollment

Location

Arms

65.7

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Delirium	Drug: Haloperidol Drug: Ketamine Drug: Haloperidol + Ketamine Drug: Saline solution (NaCl 0.9%)	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Baden PRIDe Trial - Baden Prevention and Reduction of Incidence of Postoperative Delirium Trial

Study Start Date :

Jul 1, 2013

Actual Primary Completion Date :

Dec 21, 2018

Actual Study Completion Date :

Dec 21, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Haloperidol Haloperidol 0.005mg/kg at induction of anesthesia	Drug: Haloperidol Haloperidol 0.005mg/kg at induction of anesthesia
Active Comparator: Ketamine Ketamine 1mg/kg at induction of anesthesia	Drug: Ketamine Ketamine 1mg/kg at induction of anesthesia to test its power to prevent postoperative delirium
Active Comparator: Haloperidol + Ketamine Combination of Haloperidol + Ketamine in same dosage at induction of anesthesia	Drug: Haloperidol + Ketamine Haloperidol 0.005mg/kg + Ketamine 1mg/kg at induction of anesthesia to test their power to prevent postoperative delirium if given together
Placebo Comparator: Saline solution (NaCl 0.9%) Placebo	Drug: Saline solution (NaCl 0.9%) Placebo being used in one of the four groups

Outcome Measures

Primary Outcome Measures

Differences among study groups - Significant drop in MMSE of two points in one of the three postoperative follow-up days [5 day follow-up (preoperative, day of surgery, postoperative days 1-3)]
Significant drop in MMSE of two points in one of the three postoperative follow-up days (ICU patients excluded)

Secondary Outcome Measures

Quantification of incidence of postoperative delirium based on cognitive testing and lab parameters [5 day follow-up (preoperative, day of surgery, postoperative days 1-3)]
Drop of one point in Nursing Delirium Screening Scale (Nu-DESC) compared pre- and postoperatively, comparison of levels of NSE, S-100beta and Cortisol (significantly elevated postoperatively?)

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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