Diverticulitis: Antibiotics or Close Observation?

Study Overview
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Brief Summary
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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.

Official Title
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DIABOLO Trial: A Multicenter Randomized Clinical Trial Investigating the Cost-effectiveness of Treatment Strategies With or Without Antibiotics for Uncomplicated Acute Diverticulitis.

Conditions
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Diverticulitis

Intervention / Treatment
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* Drug: Amoxicillin-clavulanate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conservative strategy with antibiotics<br>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 | Drug: Amoxicillin-clavulanate<br>* Amoxicillin-clavulanate: 4 times a day 1200 mg and switch to oral administration 3 times a day 625 mg after two days, for a total duration of 10 days. In case of allergy to Amoxicillin-clavulanate: intravenous administration ciprofloxacin 2 times a day 400 mg and metronidazole 3 times a day 500 mg. In case of oral administration ciprofloxacin 2 times a day 500 mg and metronidazole 3 times a day 500 mg. For a total duration of 10 days.<br>* Other names: Augmentin.;|
| No Intervention: Liberal strategy without antibiotics<br>Admission only if discharge criteria are not met No initial antibiotics Intravenous fluids only for those not tolerating oral liquids Adequate pain relief Oral intake as tolerated Daily monitoring when admitted to the hospital Self-monitoring at home (Patient diary with temperature and VAS pain score until full recovery) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-full-recovery |  | 6 months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | e.g. antibiotic resistance/sensitivity pattern, allergy | 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 |  | 12 months follow-up | 
| Acute diverticulitis recurrence rate |  | 24 months follow-up | 
| Health status | Changes and valuation over time (compared to t=0) will be measured using generic and disease specific quality of life questionnaires (Euro-Qol 5D, Short Form 36 (SF-36) and the Gastro-intestinal Quality of Life Index (Giqli)) | 3 months follow-up | 
| Health status | Changes and valuation over time (compared to t=0 and 3 months) will be measured using generic and disease specific quality of life questionnaires (Euro-Qol 5D, Short Form 36 (SF-36) and the Gastro-intestinal Quality of Life Index (Giqli)) | 6 months follow-up | 
| Health status | Changes and valuation over time (compared to t=0, 3 and 6 months) will be measured using generic and disease specific quality of life questionnaires (Euro-Qol 5D, Short Form 36 (SF-36) and the Gastro-intestinal Quality of Life Index (Giqli)) | 12 months follow-up | 
| Health status | Changes and valuation over time (compared to t=0, 3, 6 and 12 months) will be measured using generic and disease specific quality of life questionnaires (Euro-Qol 5D, Short Form 36 (SF-36) and the Gastro-intestinal Quality of Life Index (Giqli)) | 24 months follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multicenter randomized, open label, clinical trial, acute uncomplicated (mild) diverticulitis, treatment strategies, management of diverticulitis, antibiotics, observation and supportive care, cost analysis, economic evaluation