Preventive Effect of Prophylactic Oral Antibiotics Against Cholangitis After Kasai Portoenterostomy

NCT05925309 | Recruiting DMC

• 1 other identifier: PACK
• Study Type: interventional
• Target: 356
• Locations: 1 country
• Sites: 1

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.

Conditions

Biliary Atresia; Cholangitis; Anti-Bacterial Agents

Outcome Measures

Primary Outcomes (1)

• The occurrence of cholangitis (confirmed or suspected) within 6 months after KP

  Definition of cholangitis: A. Clinical elements 1. Fever and/or shivering; 2. Stool color change; 3. New/increasing jaundice; 4. Abdominal discomfort: vomiting, poor, feeding, irritability. B. Laboratory and imaging elements 1. Inflammatory response (WBC and/or CRP and/or PCT); 2. Increased/increasing transaminases; 3. Increased/increasing GGT and/or bilirubin; 4. Bile lakes. Suspected cholangitis: one item in A + one item in B. Confirmed cholangitis: two items in A + two items in B or "suspected cholangitis" + positive blood culture. The diagnosis of cholangitis requires the exclusion of definite infections of other systems.

  6 months after KP

Secondary Outcomes (12)

• The occurrence of cholangitis (confirmed or suspected) within 1 year after KP

  1 year after KP

• The occurrence of jaundice clearance within 6 months after KP

  6 months after KP

• The occurrence of jaundice clearance within 1 year after KP

  1 year after KP

• The number of cholangitis recurrence within 6 months after KP

  6 months after KP

• The number of cholangitis recurrence within 1 year after KP

  1 year after KP

Study Arms (2)

Antibiotics group

ACTIVE COMPARATOR

Basic treatment + Prophylactic oral antibiotics

Drug: Basic treatment: sulperazone + ursodeoxycholic acid + compound glycyrrhizin + methylprednisolone + vitamin AD , D , E , K + imipenem or meropenem; Drug: Prophylactic oral antibiotics: compound sulfamethoxazole tablet (SMZ/TMP) + cefaclor

Non-antibiotics group

EXPERIMENTAL

Basic treatment

Drug: Basic treatment: sulperazone + ursodeoxycholic acid + compound glycyrrhizin + methylprednisolone + vitamin AD , D , E , K + imipenem or meropenem

Interventions

Basic treatment: sulperazone + ursodeoxycholic acid + compound glycyrrhizin + methylprednisolone + vitamin AD , D , E , K + imipenem or meropenem DRUG

Sulperazone 50mg/kg q8h is used intravenously from the first day to the 14th day after KP surgery. Ursodeoxycholic acid 20mg/kg/d p.o, starting from the 5th day after surgery for at least 2 years. Compound glycyrrhizin 20mg/d i.v, 1-4 days after operation, then switch to compound glycyrrhizin tablets 12.5mg b.i.d p.o until 6 months after KP. Methylprednisolone start at 4mg/kg/d i.v on the 8th day after operation, and decrease by 1mg/kg/d every three days. Starting at about the 15th day after operation, methylprednisolone 4mg/kg is given orally every other day, and the dose is gradually reduced at 10-12 weeks. Vitamin AD , D , E , K, are given orally from the 5th day after the KP for at least 2 months. Treatment of cholangitis: sulperazone 50mg/kg q8h i.v., and methylprednisolone could be used. If cholangitis is not controlled, imipenem or meropenem may be used.

Antibiotics group; Non-antibiotics group

Prophylactic oral antibiotics: compound sulfamethoxazole tablet (SMZ/TMP) + cefaclor DRUG

Compound sulfamethoxazole tablet (SMZ/TMP) 25 mg/kg/d p.o. and cefaclor 12.5 mg/kg/d p.o. alternately every 2 weeks, from post-operation day 15 to month 6.

Antibiotics group

Eligibility Criteria

• Age: 14 Days - 90 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead

Study Sites (1)

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

RECRUITING

Related Publications (4)

• 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.

  PMID: 35159946 BACKGROUND

• 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.

  PMID: 34013444 BACKGROUND

• 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.

  PMID: 26183324 BACKGROUND

• 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.

  PMID: 25974298 BACKGROUND

MeSH Terms

Conditions

Biliary Atresia; Cholangitis

Interventions

Ursodeoxycholic Acid; Methylprednisolone; Fumigant 93; Imipenem; Meropenem; Trimethoprim, Sulfamethoxazole Drug Combination; Cefaclor

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Digestive System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Drug Combinations; Pharmaceutical Preparations; Cephalexin; Cephalosporins; Thiazines

Central Study Contacts

Gong Chen, Phd

CONTACT

(+86)13918330650; chengongzlp@hotmail.com

Di Chen

CONTACT

(+86)18930942535; george19981206@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2023
• First Posted: June 29, 2023
• Study Start: July 1, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): July 31, 2027
• Last Updated: October 21, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)