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

NCT05750966 | Active Not Recruiting DMC

• 3 other identifiers: 2022.02922022-002624-12NL80410.029.22
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 31

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?

Conditions

Cholangitis

Keywords

antibiotics; randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• clinical cure rate by day 14 after ERCP without relapse by day 30

  Clinical cure is defined as the absence of both fever (\>38°C) and/or shaking chills, and initial presenting symptoms. Relapse is defined as the initiation of new antibiotic therapy for recurrent cholangitis, subsequent infection in the hepatic-pancreatic-biliary region, or any other subsequent infection possibly related to the initial episode of cholangitis.

  30 days

Secondary Outcomes (8)

• All-cause 90-day mortality.

  90 days

• Relapse of cholangitis within 90 days

  90 days

• Rate of any other subsequent infection requiring antibiotic therapy within 90 days.

  90 days

• Rate of subsequent infections with MDR bacteria or Clostridioides difficile within 90 days.

  90 days

• Rate of other adverse drug events within 14 days

  14 days

Study Arms (2)

Very short-course antibiotics

EXPERIMENTAL

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.

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

Standard course antibiotics

ACTIVE COMPARATOR

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.

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

Interventions

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

Also known as: ceftriaxone, gentamicin, cefuroxim, ciprofloxacin

Very short-course antibiotics

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

Also known as: ceftriaxone, gentamicin, cefuroxim, ciprofloxacin

Standard course antibiotics

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (31)

Flevoziekenhuis

Almere Stad, Flevoland, 1315 RA, Netherlands

Location

Rijnstate Ziekenhuis

Arnhem, Gelderland, 6815 AD, Netherlands

Location

Radboud umc

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Canisius Wilhelmina Ziekenhuis

Nijmegen, Gelderland, 6532 SZ, Netherlands

Location

Maastricht UMC+

Maastricht, Limburg, 6229 HX, Netherlands

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, North Brabant, 5223 GZ, Netherlands

Location

Catharina Ziekenhuis

Eindhoven, North Brabant, 5623 EJ, Netherlands

Location

Elisabeth Tweesteden Ziekenhuis

Tilburg, North Brabant, 5022 GC, Netherlands

Location

Amstelland Ziekenhuis

Amstelveen, North Holland, 1186 AM, Netherlands

Location

Amsterdam UMC

Amsterdam, North Holland, 1081 HZ, Netherlands

Location

OLVG

Amsterdam, North Holland, 1091 AC, Netherlands

Location

Spaarne Gasthuis

Hoofddorp, North Holland, 2134 TM, Netherlands

Location

Dijklander Ziekenhuis

Hoorn, North Holland, 1624 AR, Netherlands

Location

Zaans Medisch Centrum

Zaandam, North Holland, 1502 DV, Netherlands

Location

Deventer Ziekenhuis

Deventer, Overijssel, 7416 SE, Netherlands

Location

Medisch Spectrum Twente

Enschede, Overijssel, 7512 KZ, Netherlands

Location

Isala

Zwolle, Overijssel, 8025 AB, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, Provincie Friesland, 8934 AD, Netherlands

Location

Reinier de Graaf Gasthuis

Delft, South Holland, 2625 AD, Netherlands

Location

Albert Schweitzer Ziekenhuis

Dordrecht, South Holland, 3318 AT, Netherlands

Location

Groene Hart Ziekenhuis

Gouda, South Holland, 2803 HH, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, South Holland, 2333 ZA, Netherlands

Location

Alrijne Ziekenhuis

Leiderdorp, South Holland, 2353 GA, Netherlands

Location

Erasmus MC

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Maasstad Ziekenhuis

Rotterdam, South Holland, 3079 DZ, Netherlands

Location

Haaglanden Medisch Centrum

The Hague, South Holland, 2512 VA, Netherlands

Location

Meander MC

Amersfoort, Utrecht, 3813 TZ, Netherlands

Location

St. Antonius Ziekenhuis

Nieuwegein, Utrecht, 3435 CM, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Martini Ziekenhuis

Groningen, 9728 NT, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (4)

• 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.

  PMID: 28941329 BACKGROUND

• 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.

  PMID: 35953772 BACKGROUND

• 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.

  PMID: 33462749 BACKGROUND

• Overdevest AG, Sieswerda E, Haal S, Bogaards JA, Baven-Pronk MAMC, Bogte A, Boparai KS, Ter Borg F, Brink MA, van Delft F, Dik VK, Fockens P, Gilissen LPL, Hadithi M, Hazen WL, van der Heide F, den Hollander WJ, Inderson A, de Jonge PJF, Kuiken SD, Munneke JM, Perk LE, Poen AC, Poley JW, Quispel R, Scheffer RCH, Scholvinck DW, van Soest EJ, Tan ACITL, Thijs WJ, Venneman NG, Verdonk RC, van de Vrie W, Vrolijk JM, van Wanrooij RLJ, Weijenborg PW, Dijkgraaf MGW, Prins JM, Voermans RP. Antibiotic treatment for 1 day versus 4-7 days in patients with acute cholangitis after adequate endoscopic biliary drainage (COBRA): study protocol for a randomized controlled trial. Trials. 2026 Feb 14. doi: 10.1186/s13063-026-09524-7. Online ahead of print.

  PMID: 41689066 DERIVED

MeSH Terms

Conditions

Cholangitis

Interventions

Gentamicins; Cefuroxime; Ceftriaxone; Ciprofloxacin

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cefotaxime; Cephacetrile; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Patients and investigators will know in which group they are assigned.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This study is designed as an open-label multicenter non-inferiority RCT. Patients will be randomly assigned to the intervention group (one day of ABT after ERCP) or the comparator group (4 to 7 days of ABT after ERCP).

Study Record Dates

• First Submitted: February 3, 2023
• First Posted: March 2, 2023
• Study Start: July 19, 2023
• Primary Completion: March 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (31)