Clinical trial NCT05750966: Short-course Antibiotics vs Standard Course Antibiotics in Patients With Cholangitis
Official title: Very Short-course Versus Standard Course Antibiotic Therapy in Patients With Acute ChOlangitis After Adequate Endoscopic BiliaRy drAinage
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cholangitis
Keywords: antibiotics
randomized controlled trial
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2023-03-02
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: clinical cure rate by day 14 after ERCP without relapse by day 30
timeFrame: 30 days
Secondary outcomes:
measure: All-cause 90-day mortality.
timeFrame: 90 days
measure: Relapse of cholangitis within 90 days
timeFrame: 90 days
measure: Rate of any other subsequent infection requiring antibiotic therapy within 90 days.
timeFrame: 90 days
measure: Rate of subsequent infections with MDR bacteria or Clostridioides difficile within 90 days.
timeFrame: 90 days
measure: Rate of other adverse drug events within 14 days
timeFrame: 14 days
measure: Length of intensive care and hospital stay for the initial episode of cholangitis.
timeFrame: 30 days
measure: Quality of life and health utility.
timeFrame: 90 days
measure: Societal costs and cost-effectiveness/-utility
timeFrame: 90 days
Other outcomes:
Locations:
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
state: Brabant
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
state: Brabant
city: Tilburg
country: Netherlands
facility: Elisabeth Tweesteden Ziekenhuis
state: Brabant
city: Almere
country: Netherlands
facility: Flevoziekenhuis
state: Flevoland
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
state: Friesland
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
state: Gelderland
city: Nijmegen
country: Netherlands
facility: Radboud umc
state: Gelderland
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
state: Limburg
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: Noord Holland
city: Amstelveen
country: Netherlands
facility: Amstelland Ziekenhuis
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: OLVG
state: Noord-Holland
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis
state: Noord-Holland
city: Hoorn
country: Netherlands
facility: Dijklander Ziekenhuis
state: Noord-Holland
city: Zaandam
country: Netherlands
facility: Zaans Medisch Centrum
state: Noord-Holland
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
state: Overijssel
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
state: Overijssel
city: Zwolle
country: Netherlands
facility: Isala
state: Overijssel
city: Amersfoort
country: Netherlands
facility: Meander MC
state: Utrecht
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
state: Utrecht
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
state: Zuid-Holland
city: Den Haag
country: Netherlands
facility: Haaglanden Medisch Centrum
state: Zuid-Holland
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
state: Zuid-Holland
city: Gouda
country: Netherlands
facility: Groene Hart Ziekenhuis
state: Zuid-Holland
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
state: Zuid-Holland
city: Leiderdorp
country: Netherlands
facility: Alrijne Ziekenhuis
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Maasstad Ziekenhuis
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.