DIABOLO Trial: A Multicenter Randomized Clinical Trial Investigating the Cost-effectiveness of Treatment Strategies With or Without Antibiotics for Uncomplicated Acute Diverticulitis.
试验速览
- 阶段
- 4 期
- 入组人数
- 533
- 试验地点
- 23
- 主要终点
- Time-to-full-recovery
研究概览
简要总结
Rationale
The prevalence of colonic diverticular disease is increasing in Western countries. Approximately 10 to 25% of patients with diverticular disease will eventually develop an episode of acute diverticulitis. Currently conservative treatment often includes antibiotic therapy. This advice lacks sound evidence and is merely based on experts' opinion. An old clinical dogma is being clarified with this randomized trial.
Objective
Primary objective is to evaluate whether or not using antibiotics reduces to time to full recovery of an attack of uncomplicated (mild) diverticulitis. Secondary objectives are to evaluate complications, quality of life, readmission rate, recurrence rate, medical and non-medical costs, and antibiotic resistance/sensitivity in both groups.
Hypothesis
The investigators hypothesis is that in the treatment of uncomplicated (mild) acute diverticulitis, supportive treatment without antibiotics is a more cost-effective approach than conservative treatment with antibiotics with respect to time-to-recovery as primary outcome.
Study design
A randomized, open label, multicenter clinical trial comparing treatment of acute uncomplicated diverticulitis with antibiotics to observation and supportive care alone.
Study population
Patients 18 years or older are eligible for inclusion if they have a diagnosis of acute uncomplicated diverticulitis as demonstrated by imaging. Only patients with stages 1a and 1b according to Hinchey's classification or "mild" diverticulitis according to the Ambrosetti criteria are included.
Intervention
Conservative strategy with antibiotics: supportive measures and at least 48 hours of intravenous antibiotics (and therefore admittance to the hospital) and subsequently switch to oral antibiotics if tolerated (total duration of 10 days).
Control
Liberal strategy without antibiotics: supportive measures only. Observation and oral intake as tolerated. Admittance only if discharge criteria are not met on presentation.
Main study parameters/endpoints
The primary endpoint is time-to-recovery with a 6-month follow-up period. Secondary endpoints are occurrence of complicated diverticulitis requiring surgery or percutaneous treatment, morbidity, health related quality of life, readmission rate, recurrence rate, medical and non-medical costs, and antibiotic resistance/sensitivity.
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
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Only left-sided uncomplicated (mild) acute diverticulitis;
- •Clinical suspicion of acute diverticulitis. For acute diagnostic work-up: ultrasound or CT proven diverticulitis. In the case of diverticulitis-negative ultrasound in clinically suspected patients an intravenous contrast-enhanced CT scan is mandatory for confirmation of diverticulitis or exclusion of other pathology. CT for Hinchey/Ambrosetti classification (which is a CT-based classification system) is needed for all patients, but can be delayed 1 day in those with ultrasound diagnosis. Staging diverticulitis is defined according the modified Hinchey/Ambrosetti staging, only stages 1a and 1b and "mild" diverticulitis (1a Confined pericolic inflammation, 1b Confined small (smaller than 5cm) pericolic abscess) are included;
- •All patients with informed consent.
排除标准
- •Previous radiological (ultrasound and/or CT) proven episode of diverticulitis;
- •Colonic cancer;
- •Inflammatory bowel disease (ulcerative colitis, Crohn's disease);
- •Hinchey stages 2, 3 and 4 or "severe" diverticulitis according to the Ambrosetti criteria, which require surgical or percutaneous treatment;
- •Disease with expected survival of less than 6 months;
- •Contraindication for the use of the study medication (e.g. patients with advanced renal failure or allergy to antibiotics used in this study);
- •Pregnancy, breastfeeding;
- •ASA (American Society of Anaesthesiologists) classification > III;
- •Immunocompromised patients;
- •Clinical suspicion of bacteraemia (i.e. sepsis);
- •The inability of reading/understanding and filling in the questionnaires;
- •Antibiotic use in the 4 weeks before admittance.
研究组 & 干预措施
Conservative strategy with antibiotics
- Hospital admission
- Intravenous fluids and at least 48 hours of intravenous antibiotics and subsequently switch to oral antibiotics if tolerated (otherwise continuation i.v.) to complete a full 10-day treatment duration
- Adequate pain relief
- Oral intake as tolerated
- Daily monitoring
干预措施: Amoxicillin-clavulanate (Drug)
结局指标
主要结局
Time-to-full-recovery
时间窗: 6 months follow-up
次要结局
- Direct medical costs(6 months follow-up)
- Occurrence of complicated diverticulitis defined as abscess, perforation, stricture and/or fistula and need for percutaneous drainage and/or operation(24 months follow-up)
- Predefined side-effects of initial antibiotic treatment(24 months follow-up)
- Morbidity, like urinary tract infection, pneumonia, etc(24 months follow-up)
- Mortality(24 months follow-up)
- Readmission rate(6 months follow-up)
- Indirect medical costs(6 months follow-up)
- Acute diverticulitis recurrence rate(24 months follow-up)
- Health status(24 months follow-up)
研究者
M.A. Boermeester
MD, PhD
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)