Short-course Antibiotics vs Standard Course Antibiotics in Patients With Cholangitis

NCT ID: NCT05750966

Last Updated: 2026-02-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 440 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-19
• Study Completion Date: 2026-09-01

Brief Summary

The goal of this multicentre randomized controlled trial is to investigate if a very short-course of antibiotics (1 day) for cholangitis after adequate drainage is non-inferior with respect to clinical cure in comparison with a standard course of antibiotics (4 to 7 days). Secondary objectives include:

• Will a one-day course of antibiotics for cholangitis after adequate drainage be non-inferior with respect to relapse of cholangitis and mortality in comparison with a standard course of antibiotics?
• Will a one-day course of antibiotics for cholangitis after adequate drainage result in less adverse drug events in comparison with a standard course of antibiotics?
• Will a one-day course of antibiotics for cholangitis after adequate drainage reduce length of hospital stay?
• Will a one-day course of antibiotics for cholangitis after adequate drainage improve quality of life?
• Will a one-day course of antibiotics for cholangitis after adequate drainage be cost-effective?

Detailed Description

Acute cholangitis is an infection of the biliary tract which is managed with biliary drainage and antibiotic therapy (ABT). Currently the international Tokyo Guidelines 2018 (TG18) recommend 4 to 7 days of ABT after source control. The national SWAB guideline of 2020 suggests a course of one to 3 days after biliary drainage. There are no randomized studies to guide the duration of ABT for acute cholangitis. Our recent retrospective study in the Netherlands showed that a short course of ABT seems safe and more evidence is available showing that other bacterial infections, including abdominal and bloodstream infections, can be treated with a short antibiotic course than previously assumed. Hence, the hypothesis is that a very short-course of ABT for acute cholangitis is non-inferior to a course of 4 to 7 days after adequate biliary drainage.

This study is designed as a multicenter non-inferiority randomized controlled trial. Patients will be randomly assigned to the intervention group (one day of antibiotic therapy after ERCP) or the comparator group (4 to 7 days of antibiotic therapy after ERCP).

Conditions

Cholangitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Very short-course antibiotics

The antibiotic regimens will be according to the local hospital's antibiotic guideline for cholangitis (e.g. dosage form, dosage, frequency)and/or the national SWAB guideline in the Netherlands. In the experimental group, duration of ABT after adequate drainage will be 1 day. The duration will be 4 days and can be extended to 7 days in case of gram-negative bacteraemia, according to the national SWAB guideline regarding gram-negative sepsis.

Group Type: EXPERIMENTAL

cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (24 hours)

Intervention Type: DRUG

The duration of antibiotics is 24 hours after adequate biliary drainage. The choice of antibiotics will be according to local protocol and/or national Dutch SWAB guidelines. The most common antibiotics are described above, but this can differ based on allergies, local protocol or previous cultures. Drug classes may include: aminoglycosides, carbapenems, cefalosporins, fluorquinolones, sulfonamides, penicillines.

Standard course antibiotics

The antibiotic regimens will be according to the local hospital's antibiotic guideline for cholangitis, which are based on the previously mentioned national SWAB guideline. This means that the type of ABT, dosage and frequency will be comparable to the experimental group.

In the comparator group treatment duration with ABT after ERCP will be according to the international well known and widely used TG18. The duration will be 4 days and can be extended to 7 days in case of gram-negative bacteraemia, according to the national SWAB guideline regarding gram-negative sepsis.

Group Type: ACTIVE_COMPARATOR

cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (4 to 7 days)

Intervention Type: DRUG

The duration of antibiotics is 4 to 7 days after adequate biliary drainage. The choice of antibiotics will be according to local protocol and/or national Dutch SWAB guidelines. The most common antibiotics are described above, but this can differ based on allergies, local protocol or previous cultures. Drug classes may include: aminoglycosides, carbapenems, cefalosporins, fluorquinolones, sulfonamides, penicillines.

Interventions

cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (4 to 7 days)

The duration of antibiotics is 4 to 7 days after adequate biliary drainage. The choice of antibiotics will be according to local protocol and/or national Dutch SWAB guidelines. The most common antibiotics are described above, but this can differ based on allergies, local protocol or previous cultures. Drug classes may include: aminoglycosides, carbapenems, cefalosporins, fluorquinolones, sulfonamides, penicillines.

Intervention Type: DRUG

cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (24 hours)

The duration of antibiotics is 24 hours after adequate biliary drainage. The choice of antibiotics will be according to local protocol and/or national Dutch SWAB guidelines. The most common antibiotics are described above, but this can differ based on allergies, local protocol or previous cultures. Drug classes may include: aminoglycosides, carbapenems, cefalosporins, fluorquinolones, sulfonamides, penicillines.

Intervention Type: DRUG

Other Intervention Names

ceftriaxone; gentamicin; cefuroxim; ciprofloxacin; ceftriaxone; gentamicin; cefuroxim; ciprofloxacin

Eligibility Criteria

Inclusion Criteria

• Patients with acute cholangitis due to common bile duct stones, benign or malignant distal biliary obstruction or distal biliary stent dysfunction (only stents in situ for a minimum of 30 days)
• ERCP with adequate biliary drainage (all common bile duct stones are removed and/or there is adequate flow of clear bile with or without a biliary stent(s))
• Absence of fever (temperature <38.5°C) or a decrease of body temperature of at least 1°C has occurred within 24 hours after ERCP
• Age ≥ 18 years
• Written informed consent (IC)

Exclusion Criteria

• Other aetiologies of acute cholangitis (e.g. primary sclerosing cholangitis, (sub)hilar and/or intrahepatic strictures or hilar stents)
• A recurrent cholangitis (within 3 months)
• Patients with surgically altered anatomy (leading to biliary-enteric anastomosis)
• Concomitant pancreatitis, according to International Association of Pancreatology/American Pancreatic Association guidelines.[18] Acute pancreatitis is diagnosed in case of fulfilment of 2 out of 3 of the following criteria:

• Upper abdominal pain
• Serum amylase or lipase >3x ULN
• Signs of acute pancreatitis on imaging
• Concomitant cholecystitis, according to TG18 criteria.[19] Acute cholecystitis is suspected in case one item in A is met and one item in B and C.

A. Local signs of inflammation

• A1: Murphy's sign
• A2: Right upper quadrant mass/pain/tenderness B. Systemic signs of inflammation
• B1: Fever
• B2: Elevated C-reactive protein
• B3: Elevated WBC count C. Imaging findings characteristic of acute cholecystitis

• Concomitant liver abscess
• Another additional infectious diagnosis
• Admission on an Intensive Care Unit (ICU) at time of randomisation
• Use of maintenance antimicrobial therapy
• Use of immunosuppressants
• Neutropenia

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: lead

Responsible Party

Rogier P. Voermans

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Flevoziekenhuis

Almere Stad, Flevoland, Netherlands

Rijnstate Ziekenhuis

Arnhem, Gelderland, Netherlands

Radboud umc

Nijmegen, Gelderland, Netherlands

Canisius Wilhelmina Ziekenhuis

Nijmegen, Gelderland, Netherlands

Maastricht UMC+

Maastricht, Limburg, Netherlands

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, North Brabant, Netherlands

Catharina Ziekenhuis

Eindhoven, North Brabant, Netherlands

Elisabeth Tweesteden Ziekenhuis

Tilburg, North Brabant, Netherlands

Amstelland Ziekenhuis

Amstelveen, North Holland, Netherlands

Amsterdam UMC

Amsterdam, North Holland, Netherlands

OLVG

Amsterdam, North Holland, Netherlands

Spaarne Gasthuis

Hoofddorp, North Holland, Netherlands

Dijklander Ziekenhuis

Hoorn, North Holland, Netherlands

Zaans Medisch Centrum

Zaandam, North Holland, Netherlands

Deventer Ziekenhuis

Deventer, Overijssel, Netherlands

Medisch Spectrum Twente

Enschede, Overijssel, Netherlands

Isala

Zwolle, Overijssel, Netherlands

Medisch Centrum Leeuwarden

Leeuwarden, Provincie Friesland, Netherlands

Reinier de Graaf Gasthuis

Delft, South Holland, Netherlands

Albert Schweitzer Ziekenhuis

Dordrecht, South Holland, Netherlands

Groene Hart Ziekenhuis

Gouda, South Holland, Netherlands

Leids Universitair Medisch Centrum

Leiden, South Holland, Netherlands

Alrijne Ziekenhuis

Leiderdorp, South Holland, Netherlands

Erasmus MC

Rotterdam, South Holland, Netherlands

Maasstad Ziekenhuis

Rotterdam, South Holland, Netherlands

Haaglanden Medisch Centrum

The Hague, South Holland, Netherlands

Meander MC

Amersfoort, Utrecht, Netherlands

St. Antonius Ziekenhuis

Nieuwegein, Utrecht, Netherlands

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Martini Ziekenhuis

Groningen, , Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Countries

Netherlands

References

Miura F, Okamoto K, Takada T, Strasberg SM, Asbun HJ, Pitt HA, Gomi H, Solomkin JS, Schlossberg D, Han HS, Kim MH, Hwang TL, Chen MF, Huang WS, Kiriyama S, Itoi T, Garden OJ, Liau KH, Horiguchi A, Liu KH, Su CH, Gouma DJ, Belli G, Dervenis C, Jagannath P, Chan ACW, Lau WY, Endo I, Suzuki K, Yoon YS, de Santibanes E, Gimenez ME, Jonas E, Singh H, Honda G, Asai K, Mori Y, Wada K, Higuchi R, Watanabe M, Rikiyama T, Sata N, Kano N, Umezawa A, Mukai S, Tokumura H, Hata J, Kozaka K, Iwashita Y, Hibi T, Yokoe M, Kimura T, Kitano S, Inomata M, Hirata K, Sumiyama Y, Inui K, Yamamoto M. Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. J Hepatobiliary Pancreat Sci. 2018 Jan;25(1):31-40. doi: 10.1002/jhbp.509. Epub 2018 Jan 8.

Reference Type: BACKGROUND

PMID: 28941329 (View on PubMed)

Sieswerda E, Bax HI, Hoogerwerf JJ, de Boer MGJ, Boermeester M, Bonten MJM, Dekker D, van Wijk RG, Juffermans NP, Kuindersma M, van der Linden PD, Melles DC, Pickkers P, Schouten JA, Rebel JR, van Zanten ARH, Prins JM, Wiersinga WJ. The 2021 Dutch Working Party on Antibiotic Policy (SWAB) guidelines for empirical antibacterial therapy of sepsis in adults. BMC Infect Dis. 2022 Aug 11;22(1):687. doi: 10.1186/s12879-022-07653-3.

Reference Type: BACKGROUND

PMID: 35953772 (View on PubMed)

Haal S, Wielenga MCB, Fockens P, Leseman CA, Ponsioen CY, van Soest EJ, van Wanrooij RLJ, Sieswerda E, Voermans RP. Antibiotic Therapy of 3 Days May Be Sufficient After Biliary Drainage for Acute Cholangitis: A Systematic Review. Dig Dis Sci. 2021 Dec;66(12):4128-4139. doi: 10.1007/s10620-020-06820-3. Epub 2021 Jan 19.

Reference Type: BACKGROUND

PMID: 33462749 (View on PubMed)

Other Identifiers

2022-002624-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL80410.029.22

Identifier Type: OTHER

Identifier Source: secondary_id

2022.0292

Identifier Type: -

Identifier Source: org_study_id