Short-course Antibiotics Vs Standard Course Antibiotics in Patients with Cholangitis
- Conditions
- Cholangitis
- Interventions
- Drug: cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (24 hours)Drug: cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (4 to 7 days)
- Registration Number
- NCT05750966
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 440
- 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)
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Very short-course antibiotics cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (24 hours) 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. Standard course antibiotics cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (4 to 7 days) 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.
- Primary Outcome Measures
Name Time Method clinical cure rate by day 14 after ERCP without relapse by day 30 30 days 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.
- Secondary Outcome Measures
Name Time Method Relapse of cholangitis within 90 days 90 days 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.
Rate of any other subsequent infection requiring antibiotic therapy within 90 days. 90 days Subsequent infections excluding recurrent cholangitis.
Rate of subsequent infections with MDR bacteria or Clostridioides difficile within 90 days. 90 days Subsequent infections, in particular due to resistant bacteria.
Rate of other adverse drug events within 14 days 14 days Includes: rash, diarrhoea (defined as ≥3 x loose stools per day), liver function abnormalities (defined as ≥5 x upper limit of normal (ULN) elevation in alanine aminotransferase (ALT) or ≥2 x ULN elevation in alkaline phosphatase (ALP) or ≥3 x ULN elevation in ALT and simultaneous elevation of total bilirubin concentration exceeding 2 x ULN (according to European association for the Study of the Liver Clinical Practice Guidelines: Drug-induced liver injury) AND without evidence of persistent obstruction on imaging OR elevation of liver enzymes after initial decrease. Lastly, other adverse drug events includes acute kidney injury, defined as increase in serum creatinine by ≥26.5 micromol/L within 48 hours or increase in serum creatinine to ≥1.5 times baseline (according to Kidney Disease: Improving Global Outcomes guidelines).
Length of intensive care and hospital stay for the initial episode of cholangitis. 30 days Length of IC and hospital stay defined in days.
All-cause 90-day mortality. 90 days Mortality, which includes all causes.
Quality of life and health utility. 90 days This will be evaluated using the RAND-36 and EQ-5D-5L at day 7, day 30 and day 90.
Scale title (RAND-36): Research and Devevelopment-36 Minimum raw score: 45 Maximum raw score : 198 Higher scores mean a better outcome.
Scale title (EQ-5D-5L): European Quality of Life-5 Dimensions-5 Levels score Minimum score: 11111 Maximum score: 55555 Higher scores mean a worse outcome.Societal costs and cost-effectiveness/-utility 90 days The costs per cured patient without relapse and the costs per quality adjusted life year (QALY) Scale Title: Quality Adjusted Life Year. One quality-adjusted life year (QALY) is equal to 1 year of life in perfect health.QALYs are calculated by estimating the years of life remaining for a patient following a particular treatment or intervention and weighting each year with a quality-of-life score (on a 0 to 1 scale).
Minimum score: 0 Maximum score: 1 Higher scores mean a better outcome.
Trial Locations
- Locations (31)
Martini Ziekenhuis
🇳🇱Groningen, Netherlands
Jeroen Bosch Ziekenhuis
🇳🇱Den Bosch, Brabant, Netherlands
Catharina Ziekenhuis
🇳🇱Eindhoven, Brabant, Netherlands
Elisabeth Tweesteden Ziekenhuis
🇳🇱Tilburg, Brabant, Netherlands
Flevoziekenhuis
🇳🇱Almere, Flevoland, Netherlands
Medisch Centrum Leeuwarden
🇳🇱Leeuwarden, Friesland, Netherlands
Rijnstate Ziekenhuis
🇳🇱Arnhem, Gelderland, Netherlands
Radboud umc
🇳🇱Nijmegen, Gelderland, Netherlands
Canisius Wilhelmina Ziekenhuis
🇳🇱Nijmegen, Gelderland, Netherlands
Maastricht UMC+
🇳🇱Maastricht, Limburg, Netherlands
Amsterdam UMC
🇳🇱Amsterdam, Noord Holland, Netherlands
Amstelland Ziekenhuis
🇳🇱Amstelveen, Noord-Holland, Netherlands
OLVG
🇳🇱Amsterdam, Noord-Holland, Netherlands
Spaarne Gasthuis
🇳🇱Hoofddorp, Noord-Holland, Netherlands
Dijklander Ziekenhuis
🇳🇱Hoorn, Noord-Holland, Netherlands
Zaans Medisch Centrum
🇳🇱Zaandam, Noord-Holland, Netherlands
Deventer Ziekenhuis
🇳🇱Deventer, Overijssel, Netherlands
Medisch Spectrum Twente
🇳🇱Enschede, Overijssel, Netherlands
Isala
🇳🇱Zwolle, Overijssel, Netherlands
Meander MC
🇳🇱Amersfoort, Utrecht, Netherlands
St. Antonius Ziekenhuis
🇳🇱Nieuwegein, Utrecht, Netherlands
Reinier de Graaf Gasthuis
🇳🇱Delft, Zuid-Holland, Netherlands
Haaglanden Medisch Centrum
🇳🇱Den Haag, Zuid-Holland, Netherlands
Albert Schweitzer Ziekenhuis
🇳🇱Dordrecht, Zuid-Holland, Netherlands
Groene Hart Ziekenhuis
🇳🇱Gouda, Zuid-Holland, Netherlands
Leids Universitair Medisch Centrum
🇳🇱Leiden, Zuid-Holland, Netherlands
Alrijne Ziekenhuis
🇳🇱Leiderdorp, Zuid-Holland, Netherlands
Erasmus MC
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Maasstad Ziekenhuis
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands