BOLT-P3

JRCT ID: jRCT1031230709

Registered date:15/03/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Acute cholangitis
• Date of first enrollment: 15/03/2024
• Target sample size: 210
• Study type: Interventional

Intervention(s)

This study aims to verify that the efficacy of antibiotic treatment for acute cholangitis following biliary drainage in the trial treatment group, lasting 24-72 hours, is not inferior to that in the standard treatment group, which lasts 96-168 hours.

For the standard treatment group (method and type of antibiotic administration):
Antibiotics are principally administered intravenously. The administration period is 96-168 hours after sufficient biliary drainage has been achieved. To clearly differentiate from the trial treatment group, the antibiotic administration duration in this study is specifically set to 96-168 hours. Following the recommendations of Tokyo Guideline 2018 (TG18), a choice is made from aminoglycosides, carbapenems, cephalosporins, fluoroquinolones, sulfonamides, and penicillins. The specific choice of medication is not strictly defined but may be altered based on allergies, local protocols, and previous culture results.

For the trial treatment group (method and type of antibiotic administration):
Antibiotics are principally administered intravenously. The administration period is 24-72 hours after sufficient biliary drainage has been achieved. To clarify the difference from the standard treatment group, the antibiotic administration duration is specifically set to 24-72 hours. Similar to the standard treatment group, following the recommendations of TG18, a choice is made from aminoglycosides, carbapenems, cephalosporins, fluoroquinolones, sulfonamides, and penicillins. The specific choice of medication is not strictly defined but may be altered based on allergies, local protocols, and previous culture results.

Outcome(s)

• Primary Outcome: The primary outcome is defined as the rate of cases that achieve clinical cure within 14 days and survive without recurrence.

Secondary Outcome

The secondary outcomes include the following:
1. Recurrence rate within 30 days.
2. Mortality rate within 30 days.
3. Total number of days of antibiotics required for both groups within 30 days.
4. Total number of days of hospitalization required for both groups within 30 days.
5. Clinical cure rates by severity.
6. Clinical cure rates by the presence or absence of fever at the end of antibiotic treatment.
7. Clinical cure rates in elderly populations aged 75 and over.
8. Clinical cure rates by blood culture results.
9. Clinical cure rates by bile culture results.
10. Clinical cure rates based on antibiotic susceptibility prior to ERCP.
11. Clinical cure rates based on the duration of antibiotic administration prior to ERCP.
12. Clinical cure rates based on the time until ERCP procedure.
13. Clinical cure rates based on the etiology of AC.
14. Treatment costs.
15. Incidence of the following adverse events within 14 days:
(a) Rash
(b) Diarrhea (defined as three or more loose stools per day)
(c) C. difficile enteritis: when both clinical signs and experimental confirmation are met:
Clinical signs: presence of diarrhea (three or more formless stools within 24 hours).
Experimental confirmation:
Detection of C. difficile toxin A and/or toxin B in stool.
Positive stool antigen for C. difficile.
Detection from culture of C. difficile.
Detection of specific genes of C. difficile by molecular diagnostic methods such as polymerase chain reaction.
Cell change suppression by C. difficile cytotoxicity neutralization assay.
(d) Drug-induced liver injury: any of the following:
Hepatic dysfunction (alanine aminotransferase (ALT) elevation greater than 5 times upper limit of normal (ULN))
Elevation of alkaline phosphatase (ALP) greater than 2 times ULN
Elevation of ALT greater than 3 times ULN and total bilirubin concentration rising above 2 times ULN
Additionally, recurrence is indicated if, upon re-evaluation with imaging diagnostics, there is no observed worsening of biliary duct dilation or if there is a re-elevation of hepatic and biliary enzymes following an initial decrease.
(e) Acute kidney injury: if any of the following are met within 48 hours:
Serum creatinine increases by more than 26.5 umol/L (0.3 mg/dl)
Serum creatinine increases to more than 1.5 times the baseline

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Participants must meet all of the following criteria:
1.Disease: Patients diagnosed with AC in accordance with the TG18, regardless of benign or malignant nature. However, for patients with AC due to dysfunction of distal bile duct stents, inclusion is limited to those who have had a stent in place for more than 30 days.
2.Age: 18 years or older.
3.Previous Treatment: Cases where biliary obstruction has been technically successfully relieved through biliary drainage procedures with ERCP within 48 hours of hospitalization(18).
4.Consent: Written consent obtained from the patient or their legal representative for participation in this trial.

Exclude criteria

Participants will be excluded if they meet any of the following criteria:
1. Circulatory insufficiency with catecholamines at the time of ERCP.
2. Requirement for intensive care unit ICU admission.
3. Hypothermia below 35 degrees Celsius.
4. Recurrent cholangitis within 3 months.
5. Malignant or benign biliary stricture equivalent to or beyond Bismuth 2 type in the hepatic portal area, or indeterminate cause of biliary obstruction.
6. Patients with anatomical changes due to surgery such as biliary-jejunal anastomosis.
7. Concomitant pancreatitis based on International Pancreatic Society/American Pancreatic Association guidelines, meeting two of the following criteria: Upper abdominal pain, Serum amylase or lipase more than three times upper limit of normal ULN, Imaging signs of acute pancreatitis.
8. Concurrent cholecystitis according to TG18 criteria, meeting one item from A and one from B and C:
A. Local signs of inflammation: Murphy's sign, or right upper quadrant mass, pain, or tenderness.
B. Systemic signs of inflammation: fever with axillary temperature more than 37.1C, elevated C-reactive protein CRP more than 3.0 mg/dL, or elevated white blood cell WBC count more than 10,000 uL.
C. Imaging findings characteristic of acute cholecystitis.
9. Concurrent hepatic abscess.
10. Concurrent other infections.
11. Patients receiving continuous administration of antibiotics prior to registration.
12. Complications from ERCP prior to registration such as perforation, pancreatitis, bleeding, cholecystitis, cardiopulmonary diseases due to sedation; aspiration pneumonia, choking, cardiac arrest, etc.
13. Specific immunosuppressed states:
A. Use of immunosuppressants including prednisolone more than 10 mg.
B. Known human immune virus infection.
C. Neutropenia within 48 hours prior to randomization, neutrophils less than or equal to 1500 uL.
D. Autologous hematopoietic stem cell transplantation within 1 month and at any point prior to engraftment in allogeneic hematopoietic stem cell transplantation.
14. Pregnant women.
15. Other cases deemed unsuitable for the trial by the attending physician.

Related Information

• Primary Sponsor: Sakue Masuda
• Secondary Sponsor: Yoshinori Imamura