Ketamine and Postoperative Depressive Symptom-PASSION

Effect of Low-dose Ketamine on Postoperative Depressive Symptom in Patients Undergoing Intracranial Tumor Resection (PASSION)

Perioperative depression symptom (PDS) is one of the common mental comorbidity, and influences the clinical outcomes and prognosis. However, there is no rapid acting treatment to deal with it during the limited hospital stay. This study aims to determine whether ketamine could improve the depressive symptom of peirioperative patients. It will also examine the safety for administrating ketamine as an antidepressant intraoperatively. Meanwhile, it will show if ketamine could improve anxiety, postoperative pain or delirium. This trial also will bring great concerns on patients with perioperative mental health and explore the measures to improve their psycho-related prognosis.

Study Overview

• Status: Completed
• Conditions: Ketamine; Depressive Symptom; Neurosurgery; Perioperative Period
• Intervention / Treatment: Drug: Ketamine; Drug: Normal saline

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100070
    • Beijing Tiantan Hospital

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:

1. Brain tumor located supratentorial area and need to receive elective craniotomy;
2. Moderate to severe depressive symptom measured by the qualified psychiatric doctors.
3. Ages between 18 and 65 years old.
4. American Society of Anesthesiologists physical status I-III

Exclusion Criteria:

1. History of epilepsy;
2. Major depression disorder patients undergoing antidepressive therapy within 2 weeks; 3 Psychiatric illness; 4 Drug abuse; 5 History of allergy to the research drug; 6 Tumor located in the Wernick area, Broca area or the frontal pole; 7 Hyperthyroidism; 8 Patients can not cooperate with investigators on psychiatric assessments; 9 Pregnant or breast-feeding woman; 10 refuse to sign inform consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ketamine group	Drug: Ketamine; Ketamine will be administrated intravenously at dural opening, with the total dose of 0.5 mg/kg and continual infusion for 40 minutes.; Other Names: Ketamine hydrochloride
PLACEBO_COMPARATOR: normal saline group	Drug: Normal saline; Normal saline will be administrated intravenously at dural opening, with the total dose of 0.5 ml/kg and continual infusion for 40 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	≥50% reduction in MADRS scores from baseline value.The MADRS is a 10-item tool, with scores ranging from 0 to 60, and determining the severity of depression.	Postoperative 3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe pain	The incidence of severe pain within first postoperative three days, which is defined as mean and peak numerical rating scale (NRS) are higher than 5.	Postoperative 3 days.
The remission rate	The remission rate is defined as the absolute value of MADRS no more than 10.	Postoperative 3 days and discharge.
Anxiety symptom	The anxious symptom is defined as HADS score no less than 11.	Postoperative 3 days.
Postoperative delirium	Postoperative delirium will be assessed by the Confusion Assessment Method for the Intensive Care Unit Scale (CAM-ICU) at 2 hours and 1 day after surgery.	Postoperative 1 day.
Postoperative 30-day quality of life reported by KPS	The quality of life will be evaluated by Karnofsky performance status (KPS) at postoperative 30 days.	Postoperative 30 days
Psychiatric outcomes and complications	Postoperative complications include psychiatric symptoms evaluated by Brief Psychiatric Rating Scale (BPRS), manic symptoms assessed through the 11-item Young Mania Rating Scale (YMRS), and dissociative symptoms measured by the Clinician Administered Dissociative States Scale (CADSS). Moreover, postoperative complications also include aphasia, epilepsy, hemorrhage.	Postoperative 3 days and discharge.

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Publications and helpful links

General Publications

• Zhou Y, Sun W, Zhang G, Wang A, Lin S, Chan MTV, Peng Y, Wang G, Han R. Ketamine Alleviates Depressive Symptoms in Patients Undergoing Intracranial Tumor Resection: A Randomized Controlled Trial. Anesth Analg. 2021 Dec 1;133(6):1588-1597. doi: 10.1213/ANE.0000000000005752.
• Zhou Y, Peng Y, Fang J, Sun W, Zhang G, Zhen L, Wang G, Han R. Effect of low-dose ketamine on PerioperAtive depreSsive Symptoms in patients undergoing Intracranial tumOr resectioN (PASSION): study protocol for a randomized controlled trial. Trials. 2018 Aug 29;19(1):463. doi: 10.1186/s13063-018-2831-0.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 5, 2017
• Primary Completion (ACTUAL): August 24, 2018
• Study Completion (ACTUAL): November 20, 2018

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (ACTUAL): March 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 2, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 2017-03-16

Drug and device information, study documents

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