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

Official title

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

Overview

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.

Interventions

• 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).
• 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).

Primary outcome measures

• Spontaneous Bacterial Peritonitis(SBP) recurrence rate [Time frame: Within 6 months of treatment]

Secondary outcome measures (12)

• SBP recurrence rate [Time frame: 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 [Time frame: Study within one year]
• SBP infection control rate (assessing overall effectiveness, remarkable effectiveness, effectiveness, and ineffectiveness). [Time frame: 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. [Time frame: 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 [Time frame: 1 week of treatment, 2 weeks of treatment]
• Changes in inflammation markers from baseline [Time frame: After 2 weeks and 24 weeks of treatment]
• Changes in gut barrier function compared to baseline [Time frame: After 2 weeks and 24 weeks of treatment]
• Changes in immunological test indicators from baseline [Time frame: After 2 weeks and 24 weeks of treatment]
• Changes in Child-Pugh score from baseline [Time frame: 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). [Time frame: Within 24 and 48 weeks of treatment]
• Incidence of diarrhea [Time frame: Within 24 weeks of treatment]
• Antibiotic usage [Time frame: Within 24 weeks of treatment]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Prevention

Study locations

China · 30 centers

• Fuyang People's Hospital — Fuyang
• Mengchao Hepatobiliary Hospital Of Fujian Medical University — Fuzhou
• The First Affiliated Hospital of Xiamen University — Xiamen
• Xiamen Hospital of T.C.M. — Xiamen
• The First Hospital of Lanzhou University — Lanzhou
• Guangzhou Eighth PeoPle's Hospital,Guangzhou medical University — Guangzhou
• Peking University Shenzhen Hospital — Shenzhen
• Shenzhen Third People's Hospital — Shenzhen
• … and 22 more centers

Identifiers

NCT: NCT07686861 · SLK-SBP-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗