The Prevention of Delirium and Complications Associated With Surgical Treatments Multi Center Clinical Trial (PODCAST)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Washington University School of Medicine
Sponsor:
Collaborators:
Asan Medical Center
Weill Medical College of Cornell University
Harvard Medical School
Medical College of Wisconsin
Memorial Sloan-Kettering Cancer Center
Postgraduate Institute of Medical Education and Research
University of Bern
University of Michigan
University of Manitoba
University Health Network, Toronto
Virginia Mason Hospital/Medical Center
Information provided by (Responsible Party):
Michael Avidan, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01690988
First received: August 7, 2012
Last updated: March 14, 2014
Last verified: March 2014
  Purpose

Delirium is a medical term or condition that includes a temporary inability to focus attention and to think clearly. Delirium occurs commonly (10% to 70%) in patients older than 60 undergoing large surgeries. The purpose of this study is to test rigorously whether a drug called ketamine can decrease the chance that patients will experience delirium after their surgery. The investigators are also testing whether ketamine decreases postoperative pain, postoperative opioid consumption, postoperative nausea and vomiting, ICU and hospital length of stay, and adverse outcomes (e.g. hallucinations and nightmares).


Condition Intervention Phase
Delirium
Drug: Ketamine (0.5 mg/kg)
Drug: Normal Saline (placebo)
Drug: Ketamine (1 mg/kg)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Prevention of Delirium and Complications Associated With Surgical Treatments Multi Center Clinical Trial

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Delirium [ Time Frame: Prior to surgery (baseline assessment upon study enrollment) and postoperative days 0-3 (afternoon/evening on postoperative day 0, morning and afternoon/evening on postoperative days 1-3 with at least six hours between assessments) ] [ Designated as safety issue: No ]
    According to Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit criteria


Secondary Outcome Measures:
  • Acute pain [ Time Frame: Prior to surgery (baseline assessment upon study enrollment) and postoperative days 0-3 (afternoon/evening on postoperative day 0, morning and afternoon/evening on postoperative days 1-3 with at least six hours between assessments) ] [ Designated as safety issue: No ]
    Assessed by observer-based Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) with subsequent administration of patient-reported Visual Analog Scale

  • Postoperative opioid consumption [ Time Frame: Postoperative days 0-3 ] [ Designated as safety issue: No ]
    Assessed from patients' medical charts.

  • Postoperative nausea and vomiting [ Time Frame: Postoperative days 0-3 ] [ Designated as safety issue: No ]
    Assessed from patient-reported postoperative nausea and vomiting section of Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated)

  • ICU and/or hospital length of stay [ Time Frame: Postoperative period ] [ Designated as safety issue: No ]
    Assessed from patients' medical charts

  • Adverse outcomes (e.g. hallucinations and nightmares) [ Time Frame: Postoperative days 0-3 ] [ Designated as safety issue: Yes ]
    Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit


Estimated Enrollment: 600
Study Start Date: February 2014
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketamine (0.5 mg/kg)
Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
Drug: Ketamine (0.5 mg/kg)
Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
Other Name: Ketalar
Placebo Comparator: Normal saline (placebo)
Intravenous normal saline
Drug: Normal Saline (placebo)
Normal saline IV following induction of anesthesia or administration of sedative medications
Other Name: Normal saline
Experimental: Ketamine (1 mg/kg)
Low dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
Drug: Ketamine (1 mg/kg)
Low dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
Other Name: Ketalar

Detailed Description:

Postoperative delirium is one of the most common complications of major surgery, affecting between 10% and 70% of all elderly surgical patients. Delirium manifests as poor attention and inability to think logically, and is associated with longer intensive care unit and hospital stay, long lasting cognitive deterioration, and increased mortality rate. Studies have shown that a low sub-anesthetic dose of ketamine, an anesthetic drug, has the potential to decrease several postoperative complications, including delirium, pain, opioid consumption, and nausea and vomiting. Low dose ketamine would be particularly appealing as a drug to prevent delirium and other postoperative complications, as it is inexpensive and extremely safe. However, these proposed benefits of ketamine in the perioperative setting have not yet been tested in a large clinical trial. The investigators are therefore proposing a pragmatic, exploratory clinical trial to support or refute the contention that low dose ketamine decreases the incidence of postoperative delirium, with the possibility of conducting a larger randomized clinical trial pending the results of this study. At the time of enrollment, patients will undergo the same delirium and pain evaluation that will be used postoperatively. Additionally patients will be screened for functional dependence using the Barthel Index of Activities of Daily Living, for depression using the Geriatric Depression Scale - Short Form, and for obstructive sleep apnea using the STOP-Bang criteria. They will also be asked about any falls they have experienced in the six months prior to surgery. Comorbid conditions, including the components of the Charlson Comorbidity Index, will be obtained by reviewing the patients' medical records. Any available preoperative lab results, including electrolytes and blood counts, will also be recorded.

Patients will be randomized to receive low dose ketamine or placebo following induction of anesthesia and prior to surgical incision. Blinded observers will assess delirium on the afternoon/evening of postoperative day 0 (if feasible) and twice daily (morning and afternoon/evening with at least six hours between assessments) on postoperative days 1-3 using the Confusion Assessment Method or the Confusion Assessment Method for Intensive Care Unit. Acute pain will be assessed via the observer-based Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) with subsequent administration of the patient-reported Visual Analog Scale from postoperative days 0-3. Postoperative opioid consumption will be assessed from the patients' medical charts for postoperative days 0-3. Postoperative nausea and vomiting will be assessed via a patient-reported section of the Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) for postoperative days 0-3. ICU and/or hospital length of stay will be assessed from the patients' medical charts. Adverse outcomes (e.g. hallucinations and nightmares) will be assessed via the Confusion Assessment Method or the Confusion Assessment Method for Intensive Care Unit for postoperative days 0-3.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients 60 and older
  • Competent to provide informed consent
  • Undergoing major surgery (e.g., open cardiac surgery, open or thoracoscopic thoracic surgery, abdominal surgery, open urological surgery, open gynecological surgery, major orthopedic surgery, major vascular surgery including endovascular procedures, major ear, nose and throat surgery).

Exclusion Criteria:

  • Patients with an allergy to ketamine
  • Those in whom a significant elevation of blood pressure would constitute a serious hazard (e.g., pheochromocytoma, aortic dissection)
  • Unable to provide informed consent
  • Patients with drug misuse history (e.g., ketamine, cocaine, heroin, amphetamine, methamphetamine, MDMA, phencyclidine, lysergic acid, mescaline, psilocybin)
  • Patients taking anti-psychotic medications (e.g., chlorpromazine, clozapine, olanzapine, risperidone, haloperidol, quetiapine, risperidone, paliperidone, amisulpride, sertindole)
  • Patients with a weight outside the range 50 kg - 200 kg (110 lbs - 440 lbs)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01690988

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Michael Avidan, MD    314-747-4155    avidanm@anest.wustl.edu   
Principal Investigator: Michael Avidan, MD         
Sponsors and Collaborators
Washington University School of Medicine
Asan Medical Center
Weill Medical College of Cornell University
Harvard Medical School
Medical College of Wisconsin
Memorial Sloan-Kettering Cancer Center
Postgraduate Institute of Medical Education and Research
University of Bern
University of Michigan
University of Manitoba
University Health Network, Toronto
Virginia Mason Hospital/Medical Center
Investigators
Principal Investigator: George A Mashour, MD PhD University of Michigan
Study Director: Daniel A Emmert, MD PhD Washington University School of Medicine
Study Director: Kane Pryor, MBBS Cornell
Study Director: Eric Jacobsohn, MB ChB University of Manitoba
Study Director: Judith Hudetz, PhD Medical College of Wisconsin
Study Chair: Hilary P Grocott, MD University of Manitoba
Principal Investigator: Michael S Avidan, MBBCh Washington University School of Medicine
Study Director: Sharon Inouye Harvard Medical School
Study Director: Robert Veselis Memorial Sloan Kettering Medical Center
Study Director: Jayant Aveek Postgraduate Institute of Medical Education and Research
Study Director: Heiko Kaiser University of Bern
Study Chair: Stephen Choi University of Toronto
Study Chair: Ryan Pong Virginia Mason Medical Center
Study Director: Gyujeong Noh Asan Medical Center
  More Information

No publications provided

Responsible Party: Michael Avidan, Director, Institute of Quality Improvement, Research & Informatics, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01690988     History of Changes
Other Study ID Numbers: 201206071
Study First Received: August 7, 2012
Last Updated: March 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
Delirium
ketamine
surgery
neurological complications

Additional relevant MeSH terms:
Delirium
Delirium, Dementia, Amnestic, Cognitive Disorders
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Mental Disorders
Anesthetics
Ketamine
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014