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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01690988
Recruitment Status : Completed
First Posted : September 24, 2012
Results First Posted : May 2, 2018
Last Update Posted : June 6, 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

Tracking Information
First Submitted Date  ICMJE August 7, 2012
First Posted Date  ICMJE September 24, 2012
Results First Submitted Date  ICMJE September 15, 2017
Results First Posted Date  ICMJE May 2, 2018
Last Update Posted Date June 6, 2018
Actual Study Start Date  ICMJE February 1, 2014
Actual Primary Completion Date June 26, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 21, 2012)
Incidence of postoperative delirium [ Time Frame: Within three days of surgery ]
According to Confusion Assessment Method or Confusion Assessment Method for Intensive Care Unit criteria
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2018)
  • 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.
  • 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)
  • 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.
  • ICU and/or Hospital Length of Stay [ Time Frame: Postoperative period ]
    Assessed from patients' medical charts
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2012)
  • Postoperative Acute Pain [ Time Frame: Within three postoperative days ]
    Assessed by visual analog pain scale
  • Postoperative chronic pain [ Time Frame: Within three to six months postoperatively ]
    Assessed by the self-report Brief Pain Inventory short form
  • Depressive symptoms [ Time Frame: Three to six months postoperative ]
    Assessed by PROMIS (Patient-Reported Outcomes Measurement Information System) self report 8-item short form
  • Postoperative affect [ Time Frame: Three to six months postoperatively ]
    Assessed by the PANAS (Positive and Negative Affect Schedule)
  • Post-traumatic Stress Disorder Symptoms [ Time Frame: Three to six months postoperative ]
    Assessed by the self-report PCL-S (Post-traumatic Stress Disorder Checklist - Specific)
  • Quality of Life [ Time Frame: Three months to one year postoperative ]
    Assessed by the RAND-12 short form
  • Postoperative mortality [ Time Frame: Up to five years postoperatively ]
    Assessed from the Social Security Death Index
  • Intensive Care Unit Length of Stay [ Time Frame: Up to three months ]
    Measured in days
  • Hospital length of stay [ Time Frame: Up to three months ]
    Measured in days
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Prevention of Delirium and Complications Associated With Surgical Treatments Multi Center Clinical Trial
Official Title  ICMJE The Prevention of Delirium and Complications Associated With Surgical Treatments Multi Center Clinical Trial
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).
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Delirium
Intervention  ICMJE
  • 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
  • Drug: Normal Saline (placebo)
    Normal saline IV following induction of anesthesia or administration of sedative medications
    Other Name: Normal saline
  • 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
Study Arms  ICMJE
  • Experimental: Ketamine (0.5 mg/kg)
    Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
    Intervention: Drug: Ketamine (0.5 mg/kg)
  • Placebo Comparator: Normal saline (placebo)
    Intravenous normal saline
    Intervention: Drug: Normal Saline (placebo)
  • Experimental: Ketamine (1 mg/kg)
    Low dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.
    Intervention: Drug: Ketamine (1 mg/kg)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 30, 2018)
746
Original Estimated Enrollment  ICMJE
 (submitted: September 21, 2012)
2000
Actual Study Completion Date  ICMJE July 2017
Actual Primary Completion Date June 26, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01690988
Other Study ID Numbers  ICMJE 201206071
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Michael Avidan, Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE
  • 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  ICMJE
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
PRS Account Washington University School of Medicine
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP