Baden Prevention and Reduction of Incidence of Postoperative Delirium Trial (PRIDe)

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

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Delirium
• Intervention / Treatment: Drug: Haloperidol; Drug: Ketamine; Drug: Haloperidol + Ketamine; Drug: Saline solution (NaCl 0.9%)

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 Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of incidence of postoperative delirium based on cognitive testing and lab parameters	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?)	5 day follow-up (preoperative, day of surgery, postoperative days 1-3)

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Kantonsspital Baden
• Investigators: Study Director: Alexa Hollinger, MD, University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): December 21, 2018
• Study Completion (Actual): December 21, 2018

Study Registration Dates

• First Submitted: April 7, 2015
• First Submitted That Met QC Criteria: April 28, 2015
• First Posted (Estimate): May 4, 2015

Study Record Updates

• Last Update Posted (Actual): January 23, 2019
• Last Update Submitted That Met QC Criteria: January 21, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Ketamine; Cortisol; Placebo; Postoperative delirium; Haloperidol; NSE; S-100beta; MMSE; Nu-DESC; ICDSC; DOS; Combination of Haloperidol and Ketamine; Prevention of
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Anti-Dyskinesia Agents; Ketamine; Haloperidol; Haloperidol decanoate
• Other Study ID Numbers: 2013DR4089