Clinical trial NCT05925309: Preventive Effect of Prophylactic Oral Antibiotics Against Cholangitis After Kasai Portoenterostomy
Official title: Preventive Effect of Prophylactic Oral Antibiotics Against Cholangitis After Kasai Portoenterostomy in Biliary Atresia: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Biliary Atresia
Cholangitis
Anti-Bacterial Agents
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
First posted: 2023-06-29
Enrollment: 356
Sex: ALL
Minimum age (years): 14
Maximum age (years): 90
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is non-inferiority trial design. This study aimed to investigate the effect of prophylactic oral antibiotics on preventing cholangitis in biliary atresia (BA) patients after Kasai portoenterostomy (KP) by comparing the cholangitis rate in BA patients who received prophylactic oral antibiotics and those who did not. The patients were followed up for 2 years after KP.

Detailed description: Biliary atresia (BA) is a devastating inflammatory obstructive neonatal disease affecting intrahepatic and extrahepatic bile ducts. Kasai portoenterostomy (KP) is the mainstay of treatment for BA. Cholangitis is a common complication after KP, with an overall incidence of 22-93%, and an incidence of 30-70% within 6 months after KP. The mechanism of cholangitis may be intestinal bacteria ascending into the intrahepatic biliary system or bacterial colonization, etc. Common causative organisms include Klebsiella, Escherichia coli, Pseudomonas aeruginosa, Enterobacter cloacae, Acinetobacter baumannii, Streptococcus, and Salmonella typhi. There is some controversy about prophylactic antibiotics after KP, and the type, dosage and course of antibiotics in medical institutions around the world vary greatly. After years of improvement, although the postoperative management and short-term prognosis of BA have improved, the overall incidence of cholangitis has not changed much. High-quality evidence for antibiotic prophylaxis after KP remains lacking. It still remains unknown that whether long-term prophylactic oral antibiotics could benefit the patients. Long-term use of antibiotics may not only increase the burden of liver dysfunction in patients, but also lead to antibiotic resistance, intestinal flora disturbance, and increase the risk of allergies and autoimmune diseases. It is of great significance to use evidence-based medicine to find a relatively reasonable cholangitis prevention program.

This study is non-inferiority trial design. This study aimed to investigate the effect of prophylactic oral antibiotics on preventing cholangitis by comparing the cholangitis rate in BA patients who received prophylactic oral antibiotics after KP and those who did not. Patients diagnosed with type III BA and receiving KP at Children's Hospital of Fudan University will be assigned to 2 groups. Both groups received the same basic treatment, then the patients in the antibiotics group received prophylactic oral antibiotics until the 6th month after KP, while the non-antibiotics group no longer used prophylactic antibiotics until cholangitis occurred. The cholangitis rate within 6 months after KP were measured to evaluate the preventive effect of prophylactic oral antibiotics on cholangitis. The patients were followed up for 2 years after KP.

Eligibility criteria: Inclusion Criteria:

* Patients whose age of operation is 14-90 d. Sex and race are not restricted;
* Patients who are born with gestational age older than 36 weeks;
* Patients whose body weight before operation \> 2 kg;
* Patients diagnosed of type-III BA and underwent KP in Children's Hospital of Fudan University;
* The type-III BA diagnosis is based on cholangiography or operation;
* Patients whose histological features of liver biopsies are reported. HE staining and Masson staining are required, and edema, inflammation, fibrosis, and hyperplasia of intrahepatic bile duct should be reported;
* Patients who are not allergic to postoperative medications;
* Patients who haven't accepted other antibiotic or probiotic therapy.

Exclusion Criteria:

* Patients with cholestasis of non-BA disease;
* Patients who have undergone KP at other institutions;
* Patients whose pathohistological diagnosis is in doubt;
* Patients who undergo liver transplantation immediately after KP;
* Patients with other liver diseases or severe complications (e.g., severe pulmonary hypertension, renal failure, intracranial hemorrhage, etc.) requiring surgical intervention or other medical therapy;
* Patients with severe cardiac, renal, or central nerve system malformations (e.g., tetralogy of Fallot, transposition of the great arteries, cerebral dysplasia, etc.) and have poor prognosis;
* Patients judged by the researchers that they can not comply with the study requirements.

Primary outcomes:
measure: The occurrence of cholangitis (confirmed or suspected) within 6 months after KP
timeFrame: 6 months after KP
Secondary outcomes:
measure: The occurrence of cholangitis (confirmed or suspected) within 1 year after KP
timeFrame: 1 year after KP
measure: The occurrence of jaundice clearance within 6 months after KP
timeFrame: 6 months after KP
measure: The occurrence of jaundice clearance within 1 year after KP
timeFrame: 1 year after KP
measure: The number of cholangitis recurrence within 6 months after KP
timeFrame: 6 months after KP
measure: The number of cholangitis recurrence within 1 year after KP
timeFrame: 1 year after KP
measure: The patient survive with native liver or not within 2 years after KP
timeFrame: 2 years after KP
measure: The weight gain of the patients from pre-operation to 6 months post KP
timeFrame: From pre-operation to 6 months post KP
measure: The weight gain of the patients from pre-operation to 1 year post KP
timeFrame: From pre-operation to 1 year post KP
measure: Liver parameters at post-operation month 6
timeFrame: 6 months after KP
measure: Liver parameters at post-operation month 12
timeFrame: 1 year after KP
measure: Changes in intestinal flora from post-operation week 2 to month 3
timeFrame: From post-operation week 2 to month 3
measure: Changes in intestinal flora from post-operation week 2 to month 6
timeFrame: From post-operation week 2 to month 6
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
Study officials:
References:
citation: Calinescu AM, Madadi-Sanjani O, Mack C, Schreiber RA, Superina R, Kelly D, Petersen C, Wildhaber BE. Cholangitis Definition and Treatment after Kasai Hepatoportoenterostomy for Biliary Atresia: A Delphi Process and International Expert Panel. J Clin Med. 2022 Jan 19;11(3):494. doi: 10.3390/jcm11030494.
citation: Chen G, Liu J, Huang Y, Wu Y, Lu X, Dong R, Shen Z, Sun S, Jiang J, Zheng S. Preventive effect of prophylactic intravenous antibiotics against cholangitis in biliary atresia: a randomized controlled trial. Pediatr Surg Int. 2021 Aug;37(8):1089-1097. doi: 10.1007/s00383-021-04916-z. Epub 2021 May 19.
citation: Decharun K, Leys CM, West KW, Finnell SM. Prophylactic Antibiotics for Prevention of Cholangitis in Patients With Biliary Atresia Status Post-Kasai Portoenterostomy: A Systematic Review. Clin Pediatr (Phila). 2016 Jan;55(1):66-72. doi: 10.1177/0009922815594760. Epub 2015 Jul 15.
citation: Vangay P, Ward T, Gerber JS, Knights D. Antibiotics, pediatric dysbiosis, and disease. Cell Host Microbe. 2015 May 13;17(5):553-64. doi: 10.1016/j.chom.2015.04.006.