Overview

This trial is active, not recruiting.

Condition diverticulitis
Treatment amoxicillin-clavulanate
Phase phase 4
Sponsor Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborator ZonMw: The Netherlands Organisation for Health Research and Development
Start date May 2010
End date April 2013
Trial size 533 participants
Trial identifier NCT01111253, 09/233, 2009-015004-26, 80-82310-97-10039, ABR 29615, NL29615.018.09, WO 08-54

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
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
amoxicillin-clavulanate Augmentin.
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.
(No Intervention)
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)

Primary Outcomes

Measure
Time-to-full-recovery
time frame: 6 months follow-up

Secondary Outcomes

Measure
Direct medical costs
time frame: 6 months follow-up
Occurrence of complicated diverticulitis defined as abscess, perforation, stricture and/or fistula and need for percutaneous drainage and/or operation
time frame: 24 months follow-up
Predefined side-effects of initial antibiotic treatment
time frame: 24 months follow-up
Morbidity, like urinary tract infection, pneumonia, etc
time frame: 24 months follow-up
Mortality
time frame: 24 months follow-up
Readmission rate
time frame: 6 months follow-up
Indirect medical costs
time frame: 6 months follow-up
Acute diverticulitis recurrence rate
time frame: 12 months follow-up
Acute diverticulitis recurrence rate
time frame: 24 months follow-up
Health status
time frame: 3 months follow-up
Health status
time frame: 6 months follow-up
Health status
time frame: 12 months follow-up
Health status
time frame: 24 months follow-up

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

Official title DIABOLO Trial: A Multicenter Randomized Clinical Trial Investigating the Cost-effectiveness of Treatment Strategies With or Without Antibiotics for Uncomplicated Acute Diverticulitis.
Principal investigator Marie A Boermeester, MD, PhD, MSc
Trial information was received from ClinicalTrials.gov and was last updated in October 2012.
Information provided to ClinicalTrials.gov by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).