Effect of Probiotic Supplements on Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy

Study Overview
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Brief Summary
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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.

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

Conditions
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Gastric Cancer, Neoadjuvant Chemotherapy

Intervention / Treatment
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* Drug: live combined Bifidobacteriun, Lactobacillus and Enterococcus capsules


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic Group<br>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<br>* 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.<br>|
| No Intervention: Control Group<br>CG (Control Group) patients receive blank control management. | |

What is the study measuring?
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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 |