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

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ClinicalTrials.gov Identifier: NCT01690988
Recruitment Status : Completed
First Posted : September 24, 2012
Results First Posted : May 2, 2018
Last Update Posted : June 5, 2018
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

Brief Summary:
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 or disease Intervention/treatment Phase
Delirium Drug: Ketamine (0.5 mg/kg) Drug: Normal Saline (placebo) Drug: Ketamine (1 mg/kg) Phase 3

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 746 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Prevention of Delirium and Complications Associated With Surgical Treatments Multi Center Clinical Trial
Actual Study Start Date : February 1, 2014
Actual Primary Completion Date : June 26, 2016
Actual Study Completion Date : July 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Delirium
Drug Information available for: Ketamine

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Number of Patients With Incidence of Delirium Across All Patients at Baseline and Over Post-operative Days 1-3 [ Time Frame: Delirium incidence on postoperative days 1-3, calculated by any positive CAM on any day for all patients ]

    According to Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit criteria the number of patients that had any positive CAM on any day for all patients. The main effect evaluated will be to determine whether ketamine decreases delirium, table 3 of the protocol provides a useful guide for the potential findings of the current study with their implications.

    To further clarify, delirium will be assessed on the day of surgery, when possible and on the subsequent three days POD 1-3, as long as as patients remain in the hospital and are assessable (i.e., not sedated to a RASS <-3). The assessments on POD 1-3 will be done twice daily, once in the morning and once in the afternoon. The primary outcome of the study includes only the delirium incidence on POD 1-3.

    The primary comparison will be between the combined ketamine groups and the placebo group.



Secondary Outcome Measures :
  1. Daily Maximum Pain Recorded [ Time Frame: Postoperative days 1-3, two assessment daily (morning and afternoon), with at least six hours between assessments ]
    Assessed by observer-based Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) with subsequent administration of patient-reported Visual Analog Scale The behavioral pain scale has three domains and ranges from 3 to 15. The visual analog scale is a continuous scale from 0 to 100 mm. Daily Maximum Pain accounted for pain level in the AM or PM for both the VAS and the BPS/BPS-NI a higher value means a worse outcome.

  2. Median Opioid Consumption [ Time Frame: Postoperative days 0-3 ]

    Assessed from patients' medical charts. All morphine equivalent drugs consumed by patients perioperatively

    Opioid Drugs included:

    * Postoperatively while still in hospital, the list of pain medication used included Morphine, Hydromorphone, Meperidine, Nalbuphine, Oxycodone,Oxymorphone, Tramadol, bupivacaine, (Codeine, Fentanyl, Naloxone) Total Opiates (Morphine Equivalent) in milligrams The median(IQR) opioid consumption was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg)


  3. Number of Patients With Postoperative Nausea and Vomiting [ Time Frame: Postoperative days 1-3 ]

    Assessed from patient-reported postoperative nausea and vomiting section of Behavioral Pain Scale or Behavioral Pain Scale (Non-Intubated) Patients where asked whether they "currently have nausea/vomiting" AM & PM the response choices: None, Mild, Moderate, Severe Incidence of nausea\vomiting accounted for any positive reporting(Mild, moderate, or sever) Daily incidence accounted for any positive incidence AM/PM in each POD Any POD nausea/vomiting reports the incidence across day 1-3

    The incidence of nausea and or vomiting was compared across the three study groups Placebo vs. Lo-K (0.5 mg/kg) vs. Hi-K (1 mg/kg) for POD 1-3 and overall.


  4. ICU and/or Hospital Length of Stay [ Time Frame: Postoperative period ]
    Assessed from patients' medical charts

  5. Adverse Outcomes (Number of Patients With Hallucinations) [ Time Frame: Postoperative days 1-3 ]
    Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit

  6. Adverse Outcomes (Number of Patients With Nightmares) [ Time Frame: Postoperative days 1-3 ]
    Assessed via Confusion Assessment Method or Confusion Assessment Method for Intensive care Unit



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01690988


Locations
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
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

Publications of Results:
Other Publications:
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
First Posted: September 24, 2012    Key Record Dates
Results First Posted: May 2, 2018
Last Update Posted: June 5, 2018
Last Verified: November 2017

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

Additional relevant MeSH terms:
Delirium
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders
Anesthetics
Ketamine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
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