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

NCT ID: NCT01690988

Last Updated: 2018-06-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 746 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-01
• Study Completion Date: 2017-07-31

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.

Conditions

Delirium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Ketamine (0.5 mg/kg)

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

Group Type: EXPERIMENTAL

Ketamine (0.5 mg/kg)

Intervention Type: DRUG

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

Normal saline (placebo)

Intravenous normal saline

Group Type: PLACEBO_COMPARATOR

Normal Saline (placebo)

Intervention Type: DRUG

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

Ketamine (1 mg/kg)

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

Group Type: EXPERIMENTAL

Ketamine (1 mg/kg)

Intervention Type: DRUG

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

Interventions

Ketamine (0.5 mg/kg)

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

Intervention Type: DRUG

Normal Saline (placebo)

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

Intervention Type: DRUG

Ketamine (1 mg/kg)

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

Intervention Type: DRUG

Other Intervention Names

Ketalar; Normal saline; Ketalar

Eligibility 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)

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Asan Medical Center

OTHER

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: collaborator

Harvard Medical School (HMS and HSDM)

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: collaborator

Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role: collaborator

University of Bern

OTHER

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: collaborator

University of Manitoba

OTHER

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: collaborator

Virginia Mason Hospital/Medical Center

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Michael Avidan

Director, Institute of Quality Improvement, Research & Informatics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

George A Mashour, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Daniel A Emmert, MD PhD

Role: STUDY_DIRECTOR

Washington University School of Medicine

Kane Pryor, MBBS

Role: STUDY_DIRECTOR

Cornell

Eric Jacobsohn, MB ChB

Role: STUDY_DIRECTOR

University of Manitoba

Judith Hudetz, PhD

Role: STUDY_DIRECTOR

Medical College of Wisconsin

Hilary P Grocott, MD

Role: STUDY_CHAIR

University of Manitoba

Michael S Avidan, MBBCh

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Sharon Inouye

Role: STUDY_DIRECTOR

Harvard Medical School (HMS and HSDM)

Robert Veselis

Role: STUDY_DIRECTOR

Memorial Sloan Kettering Medical Center

Jayant Aveek

Role: STUDY_DIRECTOR

Post Graduate Institute of Medical Education and Research, Chandigarh

Heiko Kaiser

Role: STUDY_DIRECTOR

University of Bern

Stephen Choi

Role: STUDY_CHAIR

University of Toronto

Ryan Pong

Role: STUDY_CHAIR

Virginia Mason Medical Center

Gyujeong Noh

Role: STUDY_DIRECTOR

Asan Medical Center

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 25231491 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28576285 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30768457 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30336852 (View on PubMed)

Other Identifiers

201206071

Identifier Type: -

Identifier Source: org_study_id