Effect of Probiotic Supplements on Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy

Effect of Perioperative Probiotic Supplements on Postoperative Short-term Outcomes in Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy: A Prospective, Randomized, Controlled, Multicenter Clinical Trial

Background: Surgery can significantly improve the prognosis of patients with gastric cancer. However, some patients are at a later stage at diagnosis and need to receive neoadjuvant chemotherapy (NACT). Previous studies have shown that NACT may lead to more postoperative complications. Probiotics have the potential to reduce postoperative complications and infections, but no large sample, multicentre, randomized clinical trials have been conducted in patients with gastric cancer receiving NACT. The aim of this multicentre randomized controlled trial was to investigate the effect of probiotics on postoperative infections and other short-term outcomes in patients with gastric cancer receiving NACT.

Methods/design: This study is a prospective, multicentre RCT. This experiment will consist of two groups - an experimental group and a control group - randomly divided in a 1:1 ratio. The experimental group will receive perioperative probiotic supplement and that of the control group will receive blank control management. An estimated 318 patients will be enrolled. The main endpoint for comparison is postoperative infections between the two groups.The experimental group patients received probiotic capsules containing Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Neoadjuvant Chemotherapy
• Intervention / Treatment: Drug: live combined Bifidobacteriun, Lactobacillus and Enterococcus capsules

• Study Type: Interventional
• Enrollment (Estimated): 318
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yanbing Zhou, MD; Phone Number: 86532-82911324; Email: zhouyanbing@qduhospital.cn
• Study Contact Backup: Name: Gan Liu, MD; Phone Number: 86532-82911324; Email: docliu163@163.com

Study Locations

• China
  • Shandong
    • Qingdao, Shandong, China, 266000
      • Recruiting
      • Department of Gastrointestinal Surgery, Qingdao University Affiliated Hospital
      • Contact: Zhou Yanbing; Phone Number: 86532-82911324; Email: zhouyanbing@qduhospital.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-80 years old
• male and female
• clinical stage was T3/4N+ evaluated by CT/MR/EUS at new diagnosis (before any anti-cancer treatment) , complete 2-4 cycles preoperative chemotherapy based on 5-FU (such as SOX, FLOX, ect.) at 3-6 weeks before surgery
• ASA grade was Ⅰ~Ⅲ
• radical minimal-invasive gastrectomy via laparoscope or DaVinci is judged as possible
• histologically confirmed gastric adenocarcinoma
• ECOG score is 0~1
• patients who provide a written informed consent before entering study screening

Exclusion Criteria:

• need emergency surgery due to performation and/or obstruction
• receive antibiotics and/or glucocorticoids within 14 days before surgery
• exist bacterial infection and/or autoimmune disease and/or IBD currently
• intolerance or allergic to probiotics
• upper abdominal surgery history
• use probiotics within 7 days before intervention, such as yogurt, ect.
• participate in other clinical trials currently
• severe mental illness
• can not participate in this trial due to severe illness of other organs evaluated by researchers, such as severe cardiac insufficiency (LVEF<30%, NYHA>Ⅱ, severe arrhythmia, congestive heart failure, myocardial infarction within 6 months), liver dysfunction (Child-Pugh C), renal dysfunction (need hemodialysis)
• need simultaneous surgery
• lactation or pregnancy
• refuse to participate in this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic Group; PG (probiotic group) patients received probiotic capsules containing Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis. The intervention begins from the completion of preoperative chemotherapy to the seventh day after surgery.	Drug: live combined Bifidobacteriun, Lactobacillus and Enterococcus capsules; Probiotics capsules containing Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis. Each capsule contained>10,000,000 colony-forming units (CFUs). This drug can treat endoxemia caused by imbalance of intestinal flora.
No Intervention: Control Group; CG (Control Group) patients receive blank control management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative infectious complications	The primary outcome was the incidence of postoperative infectious complications, which were defined as bacterial infections within 30 d after surgery. The diagnosis of infectious complications was based on fever (≥38°C), elevation of C-reactive protein (CRP), specific clinical symptoms of infection, and positive bacterial culture.	up tp 30 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative recovery parameter	time to first postoperative flatus and bowel movement; time to solid food tolerance; postoperative hospital stay;	up tp 30 days after surgery
postoperative death and readmission	postoperative death and readmission within 30 days after surgery	up tp 30 days after surgery
duration of therapeutic antibiotic use	duration of therapeutic antibiotic use measured as "day"	up tp 30 days after surgery
time to postoperative adjuvant chemotherapy	durition from surgery to postoperative adjuvant chemotherapy.	up tp 30 days after surgery
European Organization for Reasearch and Treatment of Cancer Quality of Life Questionnare-Core 30 (EORTC QLQ-C30) (V3.0)	The European Organization for Reasearch and Treatment of Cancer Quality of Life Questionnare-Core 30, Higher scores for functional areas and general health indicate better functional status and quality of life, and higher scores for symptom areas indicate more symptoms or medical problems. The minimum value is 0 and maximum value is 100.	on postoperative day 30
Postgastrectomy Syndrome Assessment Scale (PGSAS)-45	Higher score means more discomfort after gastrectomy. The minimum value is 0 and maximum value is 100	on postoperative day 3, 5, and 30
visual analogue scale	from minimum 0 to maximun 10, higher score means more pain.	on postoperative day 1, 3 and 5
Leukocyte Count	unit of measurement is "*10^9/L", recorded respectively according to measure time	Postoperative, on postoperative day 1, 3 and 5
percent of neutrophile granulocyte	unit of measurement is "%", recorded respectively according to measure time	Postoperative, on postoperative day 1, 3 and 5
procalcitonin	unit of measurement is "pg/ml", recorded respectively according to measure time	Postoperative, on postoperative day 1, 3 and 5
C-reactive protein	unit of measurement is "mg/L", recorded respectively according to measure time	Postoperative, on postoperative day 1, 3 and 5
albumin	unit of measurement is "*g/L", recorded respectively according to measure time	Postoperative, on postoperative day 1, 3 and 5
prealbumin	unit of measurement is "mg/L", recorded respectively according to measure time	Postoperative, on postoperative day 1, 3 and 5
total bilirubin	unit of measurement is "μmol/L", recorded respectively according to measure time	Postoperative, on postoperative day 1, 3 and 5

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Qingdao University
• Collaborators: Qilu Hospital of Shandong University; Shandong Provincial Hospital; Shandong Cancer Hospital and Institute; Qingdao Municipal Hospital; Qianfoshan Hospital; Jinan Central Hospital; The Second Hospital of Shandong University; Yantai Yuhuangding Hospital; Shandong Jining No.1 People's Hospital; Liaocheng People's Hospital; Weihai Municipal Hospital; Weifang People's Hospital; Weifang Medical University; Binzhou People's Hospital; Binzhou Medical University; Weihai Central Hospital; Dongying People's Hospital; Rizhao People's Hospital; The People's Hospital of Jimo.Qingdao
• Investigators: Study Director: Yanbing Zhou, MD, The affiliated hospital of Qingdao university

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: May 8, 2023
• First Submitted That Met QC Criteria: June 4, 2023
• First Posted (Estimated): June 13, 2023

Study Record Updates

• Last Update Posted (Estimated): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 4, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: GISSG2023-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• 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