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

NCT01690988 | Completed Phase 3 Results DMC

• 1 other identifier: 201206071
• Study Type: interventional
• Target: 746
• Locations: 1 country
• Sites: 1

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).

Conditions

Delirium

Keywords

Delirium; ketamine; surgery; neurological complications

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Incidence of Delirium Across All Patients at Baseline and Over Post-operative Days 1-3

  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.

  Delirium incidence on postoperative days 1-3, calculated by any positive CAM on any day for all patients

Secondary Outcomes (6)

• Daily Maximum Pain Recorded

  Postoperative days 1-3, two assessment daily (morning and afternoon), with at least six hours between assessments

• Median Opioid Consumption

  Postoperative days 0-3

• Number of Patients With Postoperative Nausea and Vomiting

  Postoperative days 1-3

• ICU and/or Hospital Length of Stay

  Postoperative period

• Adverse Outcomes (Number of Patients With Hallucinations)

  Postoperative days 1-3

Study Arms (3)

Ketamine (0.5 mg/kg)

EXPERIMENTAL

Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Drug: Ketamine (0.5 mg/kg)

Normal saline (placebo)

PLACEBO COMPARATOR

Intravenous normal saline

Drug: Normal Saline (placebo)

Ketamine (1 mg/kg)

EXPERIMENTAL

Low dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Drug: Ketamine (1 mg/kg)

Interventions

Ketamine (0.5 mg/kg) DRUG

Low dose (sub-anesthetic) 0.5 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Also known as: Ketalar

Ketamine (0.5 mg/kg)

Normal Saline (placebo) DRUG

Normal saline IV following induction of anesthesia or administration of sedative medications

Also known as: Normal saline

Normal saline (placebo)

Ketamine (1 mg/kg) DRUG

Low dose (sub-anesthetic) 1 mg/kg ketamine following induction of anesthesia or administration of sedative medications.

Also known as: Ketalar

Ketamine (1 mg/kg)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Asan Medical Center: collaborator
• Weill Medical College of Cornell University: collaborator
• Harvard Medical School (HMS and HSDM): collaborator
• Medical College of Wisconsin: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator
• Post Graduate Institute of Medical Education and Research, Chandigarh: collaborator
• University of Bern: collaborator
• University of Michigan: collaborator
• University of Manitoba: collaborator
• University Health Network, Toronto: collaborator
• Virginia Mason Hospital/Medical Center: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (4)

• Avidan MS, Fritz BA, Maybrier HR, Muench MR, Escallier KE, Chen Y, Ben Abdallah A, Veselis RA, Hudetz JA, Pagel PS, Noh G, Pryor K, Kaiser H, Arya VK, Pong R, Jacobsohn E, Grocott HP, Choi S, Downey RJ, Inouye SK, Mashour GA. The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study: protocol for an international multicentre randomised controlled trial. BMJ Open. 2014 Sep 17;4(9):e005651. doi: 10.1136/bmjopen-2014-005651.

  PMID: 25231491 BACKGROUND

• Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, Veselis RA, Grocott HP, Emmert DA, Rogers EM, Downey RJ, Yulico H, Noh GJ, Lee YH, Waszynski CM, Arya VK, Pagel PS, Hudetz JA, Muench MR, Fritz BA, Waberski W, Inouye SK, Mashour GA; PODCAST Research Group. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017 Jul 15;390(10091):267-275. doi: 10.1016/S0140-6736(17)31467-8. Epub 2017 May 30.

  PMID: 28576285 RESULT

• Vlisides PE, Thompson A, Kunkler BS, Maybrier HR, Avidan MS, Mashour GA; PODCAST Research Group. Perioperative Epidural Use and Risk of Delirium in Surgical Patients: A Secondary Analysis of the PODCAST Trial. Anesth Analg. 2019 May;128(5):944-952. doi: 10.1213/ANE.0000000000004038.

  PMID: 30768457 DERIVED

• Mashour GA, Ben Abdallah A, Pryor KO, El-Gabalawy R, Vlisides PE, Jacobsohn E, Lenze E, Maybrier HR, Veselis RA, Avidan MS; PODCAST Research Group. Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Br J Anaesth. 2018 Nov;121(5):1075-1083. doi: 10.1016/j.bja.2018.03.030. Epub 2018 Sep 19.

  PMID: 30336852 DERIVED

MeSH Terms

Conditions

Delirium

Interventions

Ketamine; Saline Solution

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Michael Avidan
• Organization: Washington University School of Medicine

avidanm@wustl.edu

314-747-4155

Study Officials

• George A Mashour, MD PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• 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 DIRECTOR

• Hilary P Grocott, MD

  University of Manitoba

  STUDY CHAIR

• Michael S Avidan, MBBCh

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Sharon Inouye

  Harvard Medical School (HMS and HSDM)

  STUDY DIRECTOR

• Robert Veselis

  Memorial Sloan Kettering Medical Center

  STUDY DIRECTOR

• Jayant Aveek

  Post Graduate Institute of Medical Education and Research, Chandigarh

  STUDY DIRECTOR

• Heiko Kaiser

  University of Bern

  STUDY DIRECTOR

• Stephen Choi

  University of Toronto

  STUDY CHAIR

• Ryan Pong

  Virginia Mason Medical Center

  STUDY CHAIR

• Gyujeong Noh

  Asan Medical Center

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Institute of Quality Improvement, Research & Informatics

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: September 24, 2012
• Study Start: February 1, 2014
• Primary Completion: June 26, 2016
• Study Completion: July 1, 2017
• Last Updated: June 6, 2018
• Results First Posted: May 2, 2018

Record last verified: 2017-11

Locations

US (1)