Intraoperative Ketamine Versus Saline in Depressed Patients Undergoing Anesthesia for Non-cardiac Surgery

• ClinicalTrials.gov Identifier: NCT03861988
• Recruitment Status: Completed
• First Posted: March 5, 2019
• Last Update Posted: September 28, 2022
• Sponsor: Stanford University
• Information provided by (Responsible Party): Boris D. Heifets, Stanford University

Tracking Information

• First Submitted Date: March 1, 2019
• First Posted Date: March 5, 2019
• Last Update Posted Date: September 28, 2022
• Actual Study Start Date: August 22, 2019
• Actual Primary Completion Date: September 22, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 31, 2022)

score on Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 1 to 3 days post procedure (up to 20 minutes to complete survey) ]

This outcome measures symptoms of depression on a scales that ranges 0 to 60. A lower score indicates lower severity of symptoms. The assessment for this outcome measure will be taken once daily on days 1, 2 and 3 post procedure. A mixed model for repeated measures (MMRM) will be used to analyze the difference in postoperative MADRS score compared to pre-procedure.

Original Primary Outcome Measures (submitted: March 4, 2019)

Composite score on Hospital Anxiety and Depression Scale (HADS) and Montgomery-Asberg Depression Rating Scales (MADRS) [ Time Frame: 1 to 5 days post procedure (up to 20 minutes to complete survey) ]

This outcome measures a composite of the HADS and MADRS depression rating scales. The composite score range is 0 to 81. A lower score indicate lower severity of symptoms. The assessment for this outcome measure will be taken once between days 1 and 5 post procedure.

• Current Secondary Outcome Measures (submitted: August 31, 2022): Proportion of participants with clinical response (defined as >-50% reduction in MADRS score from baseline) [ Time Frame: 1 to 3 days post procedure (up to 20 minutes to complete survey) ]

Original Secondary Outcome Measures (submitted: March 4, 2019)

• Pain at surgical site: scale of 0-10 [ Time Frame: 1 to 5 days post procedure (up to 5 minutes to complete survey) ]
  This outcome measures average pain at the surgical site as reported by the patient on a scale of 0-10, with lower scores corresponding to less pain ("0" = no pain) and higher scores corresponding to more pain. The assessment for this outcome measure will be taken once between days 1 and 5 following the procedure.
• Pain at surgical site: scale of 0-10 [ Time Frame: 14 days post procedure (up to 5 minutes to complete survey) ]
  This outcome measures average pain at the surgical site as reported by the patient on a scale of 0-10, with lower scores corresponding to less pain ("0" = no pain) and higher scores corresponding to more pain.
• Opioid consumption [ Time Frame: 0 to 14 days post procedure ]
  This outcome measures how many cumulative morphine-equivalents milligrams of opioid pain medication the patient has taken.

Current Other Pre-specified Outcome Measures (submitted: August 31, 2022)

• score on Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Days 5, 7 and 14 days post procedure compared to pre-procedure ]
• score on Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 1 to 14 days post procedure (up to 5 minutes to complete survey) ]
  This outcome measures self-reported symptoms of anxiety and depression on a scale that ranges from 0-42. A lower score indicates lower severity of symptoms.
• Pain at surgical site: scale of 0-10 [ Time Frame: 14 days post procedure (up to 5 minutes to complete survey) ]
  This outcome measures average pain at the surgical site as reported by the patient on a scale of 0-10, with lower scores corresponding to less pain ("0" = no pain) and higher scores corresponding to more pain.
• Opioid consumption [ Time Frame: 0 to 14 days post procedure ]
  This outcome measures how many cumulative morphine-equivalents milligrams of opioid pain medication the patient has taken as an inpatient and after discharge from hospital
• Hospital length of stay [ Time Frame: through study completion, an average of 2 days. ]
  Number of days from admission (day of surgery) through discharge after surgery.
• Pain interference score [ Time Frame: 14 days post procedure (up to 5 minutes to complete survey) ]
  This self reported outcome measure the extent to which postoperative pain interferes with typical functioning in seven domains, each rated on a scale from 0 (does not interfere) to 10 (completely interferes)
• Proportion of participants with remission (defined as a MADRS score of <=12 on day 14) [ Time Frame: up to 14 days post procedure (up to 20 minutes to complete survey) ]

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Intraoperative Ketamine Versus Saline in Depressed Patients Undergoing Anesthesia for Non-cardiac Surgery
• Official Title: Double-blind Trial of Intraoperative Ketamine Versus Saline in Depressed Patients Undergoing Anesthesia for Non-cardiac Surgery
• Brief Summary: This study evaluates whether ketamine, given as part of an anesthetic, improves depression symptoms in depressed patients undergoing non-cardiac surgery. Half of participants will receive a ketamine infusion during surgery, while the other half will receive a placebo (normal saline) during surgery.
• Detailed Description: Major Depressive Disorder (MDD) is widely prevalent among patients preparing to have surgery, and is a known risk factor for complications after surgery, including wound infection, myocardial infarction and opioid use disorder. Ketamine has emerged as an effective, rapid-acting antidepressant therapy for patients with MDD, and may be a useful tool to prevent MDD-related morbidity in the perioperative period. Ketamine has been well studied for MDD in outpatient clinics where it is given as an infusion (0.5 mg/kg over 40 minutes) in awake patients. Ketamine is often used as part of an anesthetic cocktail in sedated or anesthetized patients, but it is unknown whether ketamine has an antidepressant effect in this context. The investigators will determine whether a ketamine infusion, compared to placebo (normal saline infusion), has an antidepressant effect when given during surgical anesthesia. If ketamine is an effective antidepressant in this population under anesthesia, its use could be incorporated into a set of interventions to minimize the perioperative complications associated with MDD.
• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Masking is for double blind phase only.

Primary Purpose: Treatment

Condition

• Major Depressive Disorder
• Surgery
• Orthopedic Disorder

Intervention

• Drug: Ketamine
  0.5 mg/kg over 40 minutes, intravenous.
  Other Name: Ketalar.
• Drug: Normal saline (placebo)
  Normal saline infusion over 40 minutes, equivalent volume to ketamine infusion.

Study Arms

• Experimental: Open label ketamine
  Patients will receive an intravenous ketamine infusion during surgery.
  Intervention: Drug: Ketamine
• Experimental: Double blind ketamine
  Patients will receive an intravenous ketamine infusion during surgery.
  Intervention: Drug: Ketamine
• Placebo Comparator: Double blind placebo
  Participants will receive placebo (normal saline infusion) during surgery.
  Intervention: Drug: Normal saline (placebo)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 4, 2019): 45
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: September 27, 2022
• Actual Primary Completion Date: September 22, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patient presenting for non-cardiac, non-intracranial surgery
• Major Depressive Disorder

Exclusion Criteria:

• Pregnant of breastfeeding women

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03861988
• Other Study ID Numbers: 49114
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: No current plan to share data.

• Current Responsible Party: Boris D. Heifets, Stanford University
• Original Responsible Party: Same as current
• Current Study Sponsor: Stanford University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Boris D Heifets, MD, PhD; Stanford University

• PRS Account: Stanford University
• Verification Date: September 2022