Diverticulitis: Antibiotics or Close Observation?

Diverticulitis Clinical Trial

— DIABOLO  

Official title:

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

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT01111253
• Other study ID #: 09/233
• Secondary ID: 2009-015004-26NL
• Status: Unknown status
• Phase: Phase 4
• First received: April 22, 2010
• Last updated: October 26, 2012
• Start date: May 2010
• Est. completion date: October 2014

Study information

• Verified date: October 2012
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 533
• Est. completion date: October 2014
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diverticulitis

Intervention

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.

Locations

Country	Name	City	State
Netherlands	Ziekenhuisgroep Twente	Almelo
Netherlands	Flevo Hospital	Almere
Netherlands	Meander Hospital	Amersfoort
Netherlands	Academic Medical Center	Amsterdam
Netherlands	BovenIJ Hospital	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Sint Lucas Andreas Hospital	Amsterdam
Netherlands	Slotervaart Hospital	Amsterdam
Netherlands	VU Medical Center	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	Erasmus Medical Center	Rotterdam
Netherlands	Ikazia Hospital	Rotterdam
Netherlands	Sint Franciscus Gasthuis	Rotterdam
Netherlands	Máxima Hospital	Veldhoven

Sponsors (3)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	Dutch Digestive Diseases Foundation, ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

References & Publications (6)

de Korte N, Klarenbeek BR, Kuyvenhoven JP, Roumen RM, Cuesta MA, Stockmann HB. Management of diverticulitis: results of a survey among gastroenterologists and surgeons. Colorectal Dis. 2011 Dec;13(12):e411-7. doi: 10.1111/j.1463-1318.2011.02744.x. — View Citation

de Korte N, Kuyvenhoven JP, van der Peet DL, Felt-Bersma RJ, Cuesta MA, Stockmann HB. Mild colonic diverticulitis can be treated without antibiotics. A case-control study. Colorectal Dis. 2012 Mar;14(3):325-30. doi: 10.1111/j.1463-1318.2011.02609.x. — View Citation

de Korte N, Unlü C, Boermeester MA, Cuesta MA, Vrouenreats BC, Stockmann HB. Use of antibiotics in uncomplicated diverticulitis. Br J Surg. 2011 Jun;98(6):761-7. doi: 10.1002/bjs.7376. Epub 2011 Jan 6. Review. — View Citation

Draaisma WA, van de Wall BJ, Vermeulen J, Unlu C, de Korte N, Swank HA. [Treatment for diverticulitis not thoroughly researched]. Ned Tijdschr Geneeskd. 2009;153:A648. Review. Dutch. — View Citation

Ünlü C, Daniels L, Vrouenraets BC, Boermeester MA. A systematic review of high-fibre dietary therapy in diverticular disease. Int J Colorectal Dis. 2012 Apr;27(4):419-27. doi: 10.1007/s00384-011-1308-3. Epub 2011 Sep 16. Review. — View Citation

Unlü C, de Korte N, Daniels L, Consten EC, Cuesta MA, Gerhards MF, van Geloven AA, van der Zaag ES, van der Hoeven JA, Klicks R, Cense HA, Roumen RM, Eijsbouts QA, Lange JF, Fockens P, de Borgie CA, Bemelman WA, Reitsma JB, Stockmann HB, Vrouenraets BC, Boermeester MA; Dutch Diverticular Disease 3D Collaborative Study Group. A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial). BMC Surg. 2010 Jul 20;10:23. doi: 10.1186/1471-2482-10-23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time-to-full-recovery		6 months follow-up
Secondary	Direct medical costs		6 months follow-up
Secondary	Occurrence of complicated diverticulitis defined as abscess, perforation, stricture and/or fistula and need for percutaneous drainage and/or operation		24 months follow-up
Secondary	Predefined side-effects of initial antibiotic treatment	e.g. antibiotic resistance/sensitivity pattern, allergy	24 months follow-up
Secondary	Morbidity, like urinary tract infection, pneumonia, etc		24 months follow-up
Secondary	Mortality		24 months follow-up
Secondary	Readmission rate		6 months follow-up
Secondary	Indirect medical costs		6 months follow-up
Secondary	Acute diverticulitis recurrence rate		12 months follow-up
Secondary	Acute diverticulitis recurrence rate		24 months follow-up
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   DIABOLO trial website