Clinical Study on the Effectiveness of Antibiotics Combined With Bifidobacterium Quadruple Live Tablets in Treating Cirrhosis With Spontaneous Bacterial Peritonitis and Preventing Recurrence

Clinical Study on the Effectiveness of Antibiotics Combined With Bifidobacterium Quadruple Live Tablets in Treating Cirrhosis With Spontaneous Bacterial Peritonitis and Preventing Recurrence-a Randomized, Double-blind, Placebo-controlled Multicenter Clinical Study

This is a prospective, randomized, double-blind, placebo-controlled multicenter clinical study targeting cirrhosis patients with Spontaneous Bacterial Peritonitis(SBP), aiming to evaluate whether adding Bifidobacterium quadruple probiotics can improve infection control rates and reduce SBP recurrence. Meanwhile, by extending the follow-up period into a real-world clinical observation phase, the study will assess whether Bifidobacterium quadruple probiotics can lower SBP recurrence and extend the lifespan of cirrhosis patients. The primary endpoint of the study is the recurrence rate of SBP during the double-blind treatment period. The study plans to enroll 360 patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Cirrhosis With Spontaneous Bacterial Peritonitis
• Intervention / Treatment: Drug: Bifidobacterium quadruple live tablets; Drug: Bifidobacterium quadruple live bacteria tablets placebo

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Guiqiang Wang; Phone Number: 13911405123; Email: john131212@126.com

Study Locations

• China
  • Beijing, China
    • Peking University First Hospital
  • Beijing, China
    • Beijing You'an Hospital,Capital Medical University
    • Contact: Huiguo Ding
  • Chongqing, China
    • The First Affiliated Hospital of Chongqing Medical University
    • Contact: Yongguo Li
  • Chongqing, China
    • The Second Affiliated Hospital of Chongqing Medical University
    • Contact: Jinjun Chen
  • Shanghai, China
    • Shanghai Public Health Clinical Center
    • Contact: Yinzhong Shen
  • Anhui
    • Fuyang, Anhui, China
      • Fuyang People's Hospital
      • Contact: Baogui Wang
  • Fujian
    • Fuzhou, Fujian, China
      • Mengchao Hepatobiliary Hospital Of Fujian Medical University
      • Contact: Haibing Gao
    • Xiamen, Fujian, China
      • The First Affiliated Hospital of Xiamen University
      • Contact: Xiulan Xue
    • Xiamen, Fujian, China
      • Xiamen Hospital of T.C.M.
      • Contact: Hong Cai
  • Gansu
    • Lanzhou, Gansu, China
      • The first Hospital of Lanzhou University
      • Contact: Liting Zhang
  • Guangdong
    • Guangzhou, Guangdong, China
      • Guangzhou Eighth PeoPle's Hospital,Guangzhou medical University
      • Contact: Yujuan Guan
    • Shenzhen, Guangdong, China
      • Peking University Shenzhen Hospital
      • Contact: Guoxin Hu
    • Shenzhen, Guangdong, China
      • Shenzhen Third People's Hospital
      • Contact: Qingxian Cai
  • Guangxi
    • Guigang, Guangxi, China
      • Guigang City People's Hospital
      • Contact: Riying Lv
  • Guizhou
    • Guiyang, Guizhou, China
      • The Affiliated Hospital of Guizhou Medical University
      • Contact: Jie Yang
  • Hebei
    • Qinhuangdao, Hebei, China
      • The Third Hospital Of Qinhuangdao
      • Contact: Liang Miao
  • Jiangsu
    • Nanjing, Jiangsu, China
      • The Second Hospital of Nanjing
      • Contact: Wei Ye
  • Liaoning
    • Shenyang, Liaoning, China
      • The Sixth People's Hospital Of Shenyang
      • Contact: Xiaofeng Wu
  • Shandong
    • Yantai, Shandong, China
      • Yantai Qishan Hospital
      • Contact: Dalu Song
    • Yantai, Shandong, China
      • Yantai Affiliated Hospital of Shandong Medical and Pharmaceutical University
      • Contact: Lei Zhang
  • Shanxi
    • Taiyuan, Shanxi, China
      • First Hospital of Shanxi Medical University
      • Contact: Liaoyun Zhang
    • Taiyuan, Shanxi, China
      • Shanxi Bethune Hospital
      • Contact: Yan Wang
    • Xian, Shanxi, China
      • The Second Affiliated Hospital of Xi'an Jiaotong University
      • Contact: Shuangsuo Dang
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital of Sichuan University
      • Contact: Hong Tang
    • Chengdu, Sichuan, China
      • Sichuan Provincial People's Hospital
      • Contact: Shuqiang Wang
  • Yunnan
    • Kunming, Yunnan, China
      • The Second Affiliated Hospital of Kunming Medical University
      • Contact: Yingmei Tang
    • Kunming, Yunnan, China
      • The First People's Hospital of Yunnan Province
      • Contact: Ling Zhu
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital , Zhejiang University School of Medicine
      • Contact: Xiaowei Xu
    • Ningbo, Zhejiang, China
      • Ningbo No.2 Hospital
      • Contact: Liyun Fu
    • Ningbo, Zhejiang, China
      • The Affiliated People's Hospital of Ningbo University
      • Contact: Lanman Xu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18-80, any gender
• Meets the diagnostic criteria of the Cirrhosis Ascites Diagnosis and Treatment Guidelines (2023 edition), confirmed cirrhosis ascites SBP
• At least one week before enrollment, no antibiotics or probiotics treatment
• The patient has some organ function and is expected to live more than a year. Platelets ≥50×10⁹/L, hemoglobin ≥90 g/L (patients with anemia need appropriate treatment) ALT和AST<3×ULN Serum creatinine ≤1.5×ULN and creatinine clearance ≥50 mL/min
• Voluntarily sign the informed consent form

Exclusion Criteria:

• Patients with severe liver damage (total bilirubin levels more than 5 times the upper limit of normal, mainly with elevated direct bilirubin), hepatorenal syndrome, or hepatic encephalopathy
• Patients with combined blood and other site (like lungs or urinary system) infections, or those with significant hemodynamic changes, or severe SBP infections
• Patients with both intrahepatic and extrahepatic malignant tumors, or those with a history of malignant solid tumors or blood cancers
• Patients with gastrointestinal bleeding or intestinal obstruction who need emergency treatment
• People who have had serious cardiovascular disease in the past 6 months or currently（ Researchers consider clinically significant myocardial ischemia, myocardial infarction, or unstable angina.Severe arrhythmias that researchers consider clinically significant.Heart failure at NYHA class III-IV.Other acute serious complications that are life-threatening）
• People with poorly controlled high blood pressure (defined as having a systolic pressure over 160mmHg or a diastolic pressure over 100mmHg despite treatment)
• Poorly controlled diabetes (defined as blood sugar over 16.8 mmol/L during the screening period despite treatment) or hypoglycemia (blood sugar below 2.8 mmol/L during screening)
• Select patients who have had esophageal or gastric variceal bleeding within the past 6 months, or those whom the investigator deems at risk of bleeding (if an endoscopy was done within the past 6 months, the results should be collected).
• People with a history of immune deficiencies, including being HIV positive, having other acquired or congenital immune deficiencies, having idiopathic IgA deficiency, or who have taken systemic steroids (≥10 mg/day of prednisone equivalent) or immunosuppressive drugs within 14 days before the trial or are expected to need them during the trial.
• Diagnosed with chronic obstructive pulmonary disease (COPD) and meets the GOLD 2026 Group E criteria
• Patients who are currently receiving antiviral treatment for hepatitis C virus (HCV) or have received it within 12 months before screening. Patients whose antiviral treatment for hepatitis B virus (HBV) has been less than 12 months before screening.
• Autoimmune hepatitis patients who received corticosteroid treatment in the past 6 months
• People who underwent transjugular intrahepatic portosystemic shunt (TIPS) in the past 6 months
• Patients with liver cirrhosis who have non-bacterial peritonitis caused by reasons other than SBP
• Patients who are allergic to probiotic ingredients or can't take medicine orally
• Patients with psychological or mental disorders who are unable to provide an accurate medical history or cooperate
• Pregnant or breastfeeding women
• Other researchers think these patients are not suitable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Bifidobacterium quadruple live bacteria tablets placebo; Take 4.5 g of Bifidobacterium quadruple live bacteria tablets placebo orally each time, which is 9 tablets at once, after breakfast in the morning, for 2 weeks. After 2 weeks, continue taking the Bifidobacterium quadruple live bacteria tablets placebo, but change to 1.5 g each time, which is 3 tablets, 3 times a day, taken after meals, until the end of 24 weeks.After the treatment, there's a 24-week open phase where participants can voluntarily take the tablets (1.5g three times a day).
Experimental: Treatment	Drug: Bifidobacterium quadruple live tablets; Take Bifidobacterium quadruple live tablets orally at 4.5 g per dose, which is 9 tablets at a time, once after breakfast, continuously for 2 weeks. After 2 weeks, continue taking Bifidobacterium quadruple live tablets, but switch to 1.5 g per dose, which is 3 tablets per time, three times a day, after meals, and continue until 24 weeks are completed.After the treatment, there's a 24-week open phase where participants can voluntarily take the tablets (1.5g three times a day).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Spontaneous Bacterial Peritonitis(SBP) recurrence rate	Within 6 months of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SBP recurrence rate		Within 12 weeks of treatment, within 24 weeks of the open phase
The number of days from controlling SBP infection to the first recurrence of SBP		Study within one year
SBP infection control rate (assessing overall effectiveness, remarkable effectiveness, effectiveness, and ineffectiveness).		After 2 weeks of treatment
Number of days it takes for each SBP symptom (bloating, abdominal pain, abdominal tenderness, fever) to disappear or return to normal.		During the two-week hospital stay
For patients with positive baseline ascitic fluid cultures, the pathogen clearance rate and the proportion of drug-resistant bacteria		1 week of treatment, 2 weeks of treatment
Changes in inflammation markers from baseline	We collected and checked data on IL-6, IL-10, TNF-a, CRP, PCT, white blood cell count, neutrophil count and percentage, and LPS indicators.	After 2 weeks and 24 weeks of treatment
Changes in gut barrier function compared to baseline	We collect blood samples to test DAO activity, D-LA, and zonula occludens-1 (zo-1)	After 2 weeks and 24 weeks of treatment
Changes in immunological test indicators from baseline	We check and collect data on peripheral blood CD4+, CD8+, the CD4+/CD8+ T cell ratio, and IgA, IgG, IgM levels.	After 2 weeks and 24 weeks of treatment
Changes in Child-Pugh score from baseline		2 weeks of treatment, 24 weeks of treatment, 24 weeks of open phase
The occurrence rate of complications of cirrhosis (esophageal and gastric variceal bleeding, primary liver cancer, hepatorenal syndrome, hepatopulmonary syndrome, hepatic encephalopathy, portal vein thrombosis).		Within 24 and 48 weeks of treatment
Incidence of diarrhea		Within 24 weeks of treatment
Antibiotic usage	Collect information on the types of antibiotics, dosages, frequency, and timing of use from patients using diary cards.	Within 24 weeks of treatment
16s RNA sequencing and metabolomics changes compared to baseline	Collect stool samples for 16sRNA sequencing and metabolomics	At 2 weeks and 24 weeks of treatment
Changes in NRS-2002 score from baseline		2 weeks of treatment, 24 weeks of treatment, 24 weeks of open phase
Changes in lab indicators from baseline	We focus on changes in ALB, TB, ALT, AST, PLT, PT, and blood ammonia levels from baseline.	2 weeks of treatment, 24 weeks of treatment, 24 weeks of open phase
mortality rate		Within 2 weeks and 24 weeks of treatment, and within 24 weeks of the open phase
Hospital stay	We focus on the time and rate of readmission caused by SBP recurrence.	Within 24 weeks of treatment, within 24 weeks of the open phase

Other Outcome Measures

Outcome Measure	Time Frame
Antibiotic upgrade rate	Within 2 weeks of hospitalization

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Investigators: Principal Investigator: Guiqiang Wang, Ph.D, Peking University First Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: June 16, 2026
• First Submitted That Met QC Criteria: June 29, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Bifidobacterium quadruple live tablets; Cirrhosis with spontaneous bacterial peritonitis
• Other Study ID Numbers: SLK-SBP-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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