Evaluation if Physostigmine Reduces Symptoms in Patients Who Has Developed a Delirium in Intensive Care After a Surgery

Monocenter, Double Blind, Randomised, Placebo Controlled Study to Evaluate Physostigmine for the Treatment of Delirium in Perioperative Intensive Care Medicine

Evaluation if physostigmine reduces symptoms in patients who has developed a delirium in Intensive care after a surgery

Study Overview

• Status: Unknown
• Conditions: Suspected Delirium After Elective or Emergency Heart Surgery; CAM-ICU Diagnosed Delirium
• Intervention / Treatment: Drug: Physostigmine; Other: Sodium Chloride solution

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Bertram Scheller, MD; Email: bertram.scheller@kgu.de

Study Locations

• Germany
  • Hessia
    • Frankfurt, Hessia, Germany, 60590
      • Recruiting
      • Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy
      • Principal Investigator: Bertram Scheller, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients of both genders aged > 18 years, < 85 years of ICU C1 after elective or emergency heart surgery with or without extracorporeal circulation (heart-lung machine and/or extracorporeal membrane oxygenation), with suspected delirium. (May be suspected if a patient does not show adequate improvement of vigilance 24 h after adequate reduction or stop of sedative medicine)
• Patients (>18a, <85a) with CAM-ICU diagnosed delirium
• Patients of legal capacity and patients with appointed representative

Exclusion Criteria:

• Asthma
• hypersensitivity against Physostigmine salicylate, Sodium metabisulfite, Nitrogen
• gangrene mechanical obstipation
• mechanical urinary retention
• Dystrophia myotonica
• Depolarization block after depolarising muscle relaxants
• Intoxications with "irreversibly acting" cholinesterase inhibitors
• closed head trauma
• obstructions at gastro-intestinal tract and at urinary tract
• neurological diseases
• left ventricular ejection fraction < 40%
• Simultaneous Participation in other clinical trials or participation ind other clinical trials in the last 30 days
• untreated coronary heart disease
• wish to have children, pregnancy or nursing
• patients with addictive disorder in medical history

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Physostigmine; Physostigmine administered intravenously at a dose of 24 mg + 25 min a 0,04 mg/kg milligram(s)/kilogram	Drug: Physostigmine; Other Names: Anticholium
Placebo Comparator: Sodium Chloride solution; solution administered intravenously 24 mg + 25 min a 0,04 mg/kg milligram(s)/kilogram	Other: Sodium Chloride solution; Other Names: NaCl solution as Placebo comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change of vigilance or symptoms of the delirium measured by Richmond Agitation Sedation Score (RASS)	baseline to 48 hours after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reduction of weaning time at mechanical ventilator of patients with symptoms of delirium		baseline to 48 hours after administration
change in the spontaneous EEG and auditory evoked potentials	for the spontaneous EEG, we expect a shift in the frequency characteristics, measure is the spectrogram, more precisely the amplitude per frequency (band) and the phase information derived via Fourier Transform and Wavelet transformation The paradigm of the auditory stimulation is a roving paradigm (Science 13 May 2011: Vol. 332 no. 6031 pp. 858-862 DOI: 10.1126/science.1202043 •Report Preserved Feedforward But Impaired Top-Down Processes in the Vegetative State Melanie Boly1,2,*, Marta Isabel Garrido2, Olivia Gosseries1, Marie-Aurélie Bruno1, Pierre Boveroux3, Caroline Schnakers1, Marcello Massimini4, Vladimir Litvak2, Steven Laureys1, Karl Friston2) Measures will be differences in the mismatch negativity and in the phase synchronization between electrodes	baseline to 48 hours after administration
impact of the variability of heart rate	heart rate variability is a dimensionless parameter, assessing the variability of the heart rate from ECG measures (Heart Rate Variability Conny M. A. van Ravenswaaij-Arts, MD; Louis A. A. Kollee, MD, PhD; Jeroen C. W. Hopman, MSc; Gerard B. A. Stoelinga, MD, PhD; and Herman P. van Geijn, MD, PhD [+-] Article and Author Information Ann Intern Med. 1993;118(6):436-447. doi:10.7326/0003-4819-118-6-199303150-00008 )	baseline to 48 hours
change in development of muscular force	muscular force is measured with a force gauge, measured in [Newton]	baseline up to 48 hours
Occurence of Adverse events		baseline to 4 weeks after treatment

Collaborators and Investigators

• Sponsor: PD Dr. Bertram Scheller
• Collaborators: Goethe University; Dr. Franz Köhler Chemie GmbH (study medication and labeling)
• Investigators: Principal Investigator: Bertram Scheller, MD, Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy of Goethe-University Frankfurt

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: October 17, 2013
• First Submitted That Met QC Criteria: August 11, 2014
• First Posted (Estimate): August 13, 2014

Study Record Updates

• Last Update Posted (Actual): March 10, 2017
• Last Update Submitted That Met QC Criteria: March 9, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Delirium; CAM-ICU
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease Attributes; Delirium; Emergencies; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Cholinesterase Inhibitors; Miotics; Pharmaceutical Solutions; Physostigmine
• Other Study ID Numbers: DELIcu; 2012-004082-41 (EudraCT Number)