Diverticulitis: Antibiotics or Close Observation? (DIABOLO)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Diverticulitis |
Drug: Amoxicillin-clavulanate |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | DIABOLO Trial: A Multicenter Randomized Clinical Trial Investigating the Cost-effectiveness of Treatment Strategies With or Without Antibiotics for Uncomplicated Acute Diverticulitis. |
- Time-to-full-recovery [ Time Frame: 6 months follow-up ] [ Designated as safety issue: No ]
- Direct medical costs [ Time Frame: 6 months follow-up ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: Yes ]
- Predefined side-effects of initial antibiotic treatment [ Time Frame: 24 months follow-up ] [ Designated as safety issue: Yes ]e.g. antibiotic resistance/sensitivity pattern, allergy
- Morbidity, like urinary tract infection, pneumonia, etc [ Time Frame: 24 months follow-up ] [ Designated as safety issue: Yes ]
- Mortality [ Time Frame: 24 months follow-up ] [ Designated as safety issue: Yes ]
- Readmission rate [ Time Frame: 6 months follow-up ] [ Designated as safety issue: Yes ]
- Indirect medical costs [ Time Frame: 6 months follow-up ] [ Designated as safety issue: No ]
- Acute diverticulitis recurrence rate [ Time Frame: 12 months follow-up ] [ Designated as safety issue: Yes ]
- Acute diverticulitis recurrence rate [ Time Frame: 24 months follow-up ] [ Designated as safety issue: Yes ]
- Health status [ Time Frame: 3 months follow-up ] [ Designated as safety issue: No ]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))
- Health status [ Time Frame: 6 months follow-up ] [ Designated as safety issue: No ]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))
- Health status [ Time Frame: 12 months follow-up ] [ Designated as safety issue: No ]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))
- Health status [ Time Frame: 24 months follow-up ] [ Designated as safety issue: No ]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))
| Estimated Enrollment: | 533 |
| Study Start Date: | May 2010 |
| Estimated Study Completion Date: | October 2014 |
| Estimated Primary Completion Date: | April 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
Active Comparator: Conservative strategy with antibiotics
|
Drug: Amoxicillin-clavulanate
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. Other Name: Augmentin.
|
No Intervention: Liberal strategy without antibiotics
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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.
Contacts and Locations| Netherlands | |
| Ziekenhuisgroep Twente | |
| Almelo, Netherlands | |
| Flevo Hospital | |
| Almere, Netherlands | |
| Meander Hospital | |
| Amersfoort, Netherlands | |
| Academic Medical Center | |
| Amsterdam, Netherlands | |
| VU Medical Center | |
| Amsterdam, Netherlands | |
| BovenIJ Hospital | |
| Amsterdam, Netherlands | |
| Onze Lieve Vrouwe Gasthuis | |
| Amsterdam, Netherlands | |
| Sint Lucas Andreas Hospital | |
| Amsterdam, Netherlands | |
| Slotervaart Hospital | |
| Amsterdam, Netherlands | |
| Gelre Hospitals | |
| Apeldoorn, Netherlands | |
| Rijnstate Hospital | |
| Arnhem, Netherlands | |
| Rode Kruis Hospital | |
| Beverwijk, Netherlands | |
| Reinier de Graaf Gasthuis | |
| Delft, Netherlands | |
| Albert Schweitzer Hospital | |
| Dordrecht, Netherlands | |
| Kennemer Hospital | |
| Haarlem, Netherlands | |
| Ziekenhuisgroep Twente | |
| Hengelo, Netherlands | |
| Tergooi Hospital | |
| Hilversum, Netherlands | |
| Spaarne Hospitals | |
| Hoofddorp, Netherlands | |
| Westfries Gasthuis | |
| Hoorn, Netherlands | |
| Sint Antonius Hospital | |
| Nieuwegein, Netherlands | |
| Ikazia Hospital | |
| Rotterdam, Netherlands | |
| Erasmus Medical Center | |
| Rotterdam, Netherlands | |
| Sint Franciscus Gasthuis | |
| Rotterdam, Netherlands | |
| Máxima Hospital | |
| Veldhoven, Netherlands | |
| Principal Investigator: | Marie A Boermeester, MD, PhD, MSc | Academic Medical Center - University of Amsterdam |
More Information
Additional Information:
Publications:
| Responsible Party: | M.A. Boermeester, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) |
| ClinicalTrials.gov Identifier: | NCT01111253 History of Changes |
| Other Study ID Numbers: | 09/233, 2009-015004-26, NL29615.018.09, ABR 29615, 80-82310-97-10039, WO 08-54 |
| Study First Received: | April 22, 2010 |
| Last Updated: | October 26, 2012 |
| Health Authority: | Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
|
multicenter randomized, open label, clinical trial acute uncomplicated (mild) diverticulitis treatment strategies management of diverticulitis |
antibiotics observation and supportive care cost analysis economic evaluation |
Additional relevant MeSH terms:
|
Diverticulitis Gastroenteritis Gastrointestinal Diseases Digestive System Diseases Amoxicillin Anti-Bacterial Agents Amoxicillin-Potassium Clavulanate Combination |
Clavulanic Acids Clavulanic Acid Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 19, 2013