Very Short-course Versus Standard Course Antibiotic Therapy in Patients With Acute ChOlangitis After Adequate Endoscopic BiliaRy drAinage
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 410
- 试验地点
- 31
- 主要终点
- clinical cure rate by day 14 after ERCP without relapse by day 30
研究概览
简要总结
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?
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Patients and investigators will know in which group they are assigned.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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.
干预措施: cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (24 hours) (Drug)
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.
干预措施: cefrtriaxone, gentamicin, cefuroxim, ciprofloxin or other antibiotics according to local guideline (4 to 7 days) (Drug)
结局指标
主要结局
clinical cure rate by day 14 after ERCP without relapse by day 30
时间窗: 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.
次要结局
- 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)
- Length of intensive care and hospital stay for the initial episode of cholangitis.(30 days)
- All-cause 90-day mortality.(90 days)
- Quality of life and health utility.(90 days)
- Societal costs and cost-effectiveness/-utility(90 days)
研究者
Rogier P. Voermans
Principal Investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)