Diverticulitis: Antibiotics or Close Observation? (DIABOLO)

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Status and phase: Unknown; Phase 4

Conditions: Diverticulitis

Treatments: Drug: Amoxicillin-clavulanate

Study type: Interventional

Funder types: Other

Identifiers

NCT01111253

NL29615.018.09 (Registry Identifier)

WO 08-54 (Other Grant/Funding Number)

80-82310-97-10039 (Other Grant/Funding Number)

ABR 29615 (Other Identifier)

09/233

2009-015004-26 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 533 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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533 participants in 2 patient groups

Conservative strategy with antibiotics

Active Comparator group

Description:

* 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

Treatment:

Drug: Amoxicillin-clavulanate

Liberal strategy without antibiotics

No Intervention group

Description:

* 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)