Esketamine and Perioperative Depressive Symptoms

Effect of Esketamine on Perioperative Depressive Symptoms in Patients Undergoing Major Surgery

Perioperative depressive symptoms (PDS) are common in population undergoing surgery, and this would be sharpened especially for complicated, high-risk major surgery. However, None of treatments could resolve this clinical problem during limited perioperative period. The remarkable effects of ketamine on treatment resistant depression have been verified by several clinical trials and the enantiomer S-ketamine (esketamine) showed similar antidepressant efficacy with better safety in recent studies. The efficacy and safety of esketamine administrated intra-operatively for PDS will be verified in this study. Other secondary outcomes such as anxiety, postoperative pain and psychiatric symptoms will also be investigated.

Study Overview

• Status: Recruiting
• Conditions: Depressive Symptoms; Major Surgery; Perioperative Complication; Esketamine
• Intervention / Treatment: Drug: Esketamine; Drug: Normal saline

• Study Type: Interventional
• Enrollment (Anticipated): 564
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100070
    • Recruiting
    • Beijing Tiantan Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient undergoing elective major surgery
• Ages between 18 and 65 years old
• Moderate to severe depressive symptoms ( the Patient Health Questionnaire-9 scores equal to or more than 10 and Montgomery-Åsberg Depression Rating Scale scores equal to or more than 22 )
• Signed informed consent

Exclusion Criteria:

• Patients combined with aphasia or other conditions leads that patients inability to cooperate with the metal assessments;
• Tumor related injury of the 9th, 10th, 11th, 12th cranial nerve or patients need keeping intubation after surgery;
• Medical history of psychotic or bipolar disorder;
• Laboratory evidence of hormone levels disorder due to primary diseases;
• Body Mass Index more than 30 kg/㎡;
• Child-Pugh grade B or C;
• Major depressive disorder with antidepressant therapy in the past 2 weeks before screening;
• History of adverse events to ketamine or esketamine;
• Patients with repeated suicide attempts (QIDS-SR 12-item more than or equal to 3);
• History of drug abused;
• Pregnant or breastfeeding woman.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Normal saline; Equivalent amount of normal saline will be administrated intravenously suturing incision.
Experimental: Esketamine	Drug: Esketamine; Esketamine will be administrated intravenously when suturing incision, with total dose of 0.2mg/kg and continuous infusion for 40 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depressive symptoms remission	Remission is defined as MADRS total score no more than 10	Postoperative 3-day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MADRS scores	The differences in MADRS scores	Postoperative 3-day
Depressive symptoms response	The rates of patients achieving a response	Postoperative 3-day
Severe pain	The rate of severe pain after surgery	postoperative 3-day
Side-effects and Adverse events	All drug-related adverse events during surgery or before discharge	During surgery or up to 7 days after surgery

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Publications and helpful links

General Publications

• Zhou Y, Ma B, Sun W, Wang J, Fu Y, Wang A, Wang G, Han R. Effect of esketamine on perioperative depressive symptoms in major surgery patients (PASSION II): study protocol for a randomised controlled trial. BMJ Open. 2022 Apr 26;12(4):e056713. doi: 10.1136/bmjopen-2021-056713.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: Z191100006619067

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The datasets will be available from the primary investigator (Ruquan Han, Email: ruquan.han@ccmu.edu.cn) upon reasonable request after the publication of the study results.
• IPD Sharing Time Frame: After the publication of the study results.
• IPD Sharing Access Criteria: Publication in peer reviewed journal
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No