Effect of Neoadjuvant Anti-PD-1 Immunotherapy on Perioperative Analgesia and Postoperative Delirium

Clinical Observation of the Effect of Neoadjuvant Anti-PD-1 Immunotherapy on Perioperative Analgesia and Postoperative Delirium in Patients With Non-small Cell Lung Cancer

To observe the effect of preoperative anti-PD-1 monotherapy combined with chemotherapy on patients' perioperative pain and opioid analgesia, and evaluate its effect on the incidence and severity of patients' postoperative delirium.

Study Overview

• Status: Completed
• Conditions: Delirium; Analgesia; NSCLC; Immunotherapy
• Intervention / Treatment: Drug: neoadjuvant immunotherapy; Drug: Neoadjuvant chemotherapy

Detailed Description

In this study, the investigators intend to select patients with resectable NSCLC treated with immuno-neoadjuvant therapy in combination with chemotherapy, systematically observe the effect of preoperative anti-PD-1 monotherapy on patients' perioperative pain and opioid analgesia, and evaluate its effect on the incidence and severity of patients' postoperative delirium, in order to provide a clinical basis for the perioperative management of patients treated with immuno-neoadjuvant therapy and promote their postoperative recovery.

• Study Type: Observational
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • Tianjin Medical University General Hospital
  • Tianjin, China
    • Tianjin Chest Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with NSCLC receiving neo-adjuvant chemotherapy or chemotherapy combined with immunotherapy followed by radical surgery will be screened and recruited in this study.

Description

Inclusion Criteria:

• Histologically confirmed stage II or stage IIIA non-small cell lung cancer (NSCLC) and meet the requirements for R0 resection;
• American Society of Anesthesiologists (ASA): I-III, age ≥18 years, body mass index (BMI): 18.5-30;
• Normal function of Coagulation and vital organs such as heart, lungs, kidney, and liver;
• Eligible to receive platinum-containing two-drug chemotherapy;
• Sign the informed consent form

Exclusion Criteria

• Prior treatment of any kind for current lung cancer, including chemotherapy, radiation or targeted therapy;
• Preoperative opioid analgesia;
• Severe chronic or active infection requiring systemic antibacterial, antifungal or antiviral therapy, including tuberculosis infection;
• History of antipsychotic medication in the last 6 months;
• Preoperative Mini-mental state examination (MMSE) score <23

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
neoadjuvant immunotherapy group; Anti-PD-1 monoclonal antibody (Nivolumab，Pembrolizumab, Sintilimab, or Sugemalimab) 200 mg intravenously in combination with cis-platinum and paclitaxel/pemetrexed	Drug: neoadjuvant immunotherapy; Anti-PD-1 antibody was added to the conventional neoadjuvant chemotherapy.; Other Names: anti-PD-1 therapy
control group; platinum-containing dual-agent chemotherapy(cis-platinum and paclitaxel/pemetrexed)	Drug: Neoadjuvant chemotherapy; Cis-platinum combined with paclitaxel or pemetrexed; Other Names: Cis-platinum combined with paclitaxel or pemetrexed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
perioperative opioids consumption	the amount of sufentanil, remifentanil and morphine application.	from beginning of surgery to day 3 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative delirium	record the occurrence of postoperative delirium after surgery using the 3D-CAM test. Patient with postoperative delirium means worse outcome.	within 3 days after surgery
score of Numerical Rating Scale	Record the patient's resting and motor Numerical Rating Scale (NRS) scores, range from 0 to 10, and higher score means more pain.	at the time of admission to the operating room, immediately after and at 24 hour, 48 hour, and 72h after entering the PICU
analgesic pump press in PICU	the time of first analgesic pump press and no. of total press in PICU	day 1, 2 and 3 after surgery
Percent of patients with moderate to severe pain within 72 hours	Moderate to severe pain is defined as any NRS pain score of 4 or higher.	up to 72 hours after surgery
intraoperative opioid consumption	the amount of sufentanil and remifentanil	from the beginning to the end of the surgery
postoperative opioid consumption	opioid usage in PCIA and supplemental analgesics within 72 h	up to 72 hours after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
dosage of sedatives	usage of propofol	intraoperative
level of cytokines	IL-6, IL-10, TNF-α, sPD-L1	before surgery and up to 24 hour after surgery
Pathologic complete response (pCR) rate	0% viable tumor in resected esophagus and lymph nodes	up to 30 days after surgery
ration of R0 resection	surgical margin is microscopically-negative for residual tumor	up to 30 days after surgery

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Collaborators: Tianjin Medical University General Hospital; Tianjin Chest Hospital
• Investigators: Principal Investigator: Kaiyuan Wang, MD, Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2022
• Primary Completion (Actual): December 20, 2023
• Study Completion (Actual): January 2, 2024

Study Registration Dates

• First Submitted: October 7, 2021
• First Submitted That Met QC Criteria: March 1, 2022
• First Posted (Actual): March 10, 2022

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Emergence Delirium; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Folic Acid Antagonists; Paclitaxel; Pemetrexed
• Other Study ID Numbers: bc2021131

Drug and device information, study documents

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