Open Access Highly Accessed Study protocol

A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial)

Çağdaş Ünlü12*, Niels de Korte3, Lidewine Daniels2, Esther CJ Consten4, Miguel A Cuesta5, Michael F Gerhards6, Anna AW van Geloven7, Edwin S van der Zaag8, Joost AB van der Hoeven9, Rutger Klicks10, Huib A Cense11, Rudi MH Roumen12, Quirijn AJ Eijsbouts13, Johan F Lange14, Paul Fockens15, Corianne AJM de Borgie16, Wilem A Bemelman2, Johannes B Reitsma16, Hein BAC Stockmann3, Bart C Vrouenraets1, Marja A Boermeester2 and Dutch Diverticular Disease (3D) Collaborative Study Group

Author Affiliations

1 Department of Surgery, Sint Lucas Andreas Hospital Amsterdam, the Netherlands

2 Department of Surgery, Academic Medical Center Amsterdam, the Netherlands

3 Department of Surgery, Kennemer Gasthuis, Haarlem, the Netherlands

4 Department of Surgery, Meander Medisch Centrum Amersfoort, the Netherlands

5 Department of Surgery, VU Medical Center Amsterdam, the Netherlands

6 Department of Surgery, Onze Lieve Vrouwe Gasthuis Amsterdam, the Netherlands

7 Department of Surgery, Tergooi Hospital Hilversum, the Netherlands

8 Department of Surgery, Gelre Hospital Apeldoorn, the Netherlands

9 Department of Surgery, Albert Schweitzer Hospital Dordrecht, the Netherlands

10 Department of Surgery, Boven IJ Hospital Amsterdam, the Netherlands

11 Department of Surgery, Rode Kruis Hospital Beverwijk, the Netherlands

12 Department of Surgery, Maxima Medisch Centrum Veldhoven, the Netherlands

13 Department of Surgery, Spaarne Hospital Hoofddorp, the Netherlands

14 Department of Surgery, Erasmus Medical Center Rotterdam, the Netherlands

15 Department of Gastroenterology, Academic Medical Center Amsterdam, the Netherlands

16 Department of Clinical Epidemiology and Biostatistics, Academic Medical Center Amsterdam, the Netherlands

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BMC Surgery 2010, 10:23  doi:10.1186/1471-2482-10-23

Published: 20 July 2010

Abstract

Background

Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts' opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects.

Methods

A randomized multicenter pragmatic clinical trial comparing two treatment strategies for uncomplicated acute diverticulitis. I) A conservative strategy with antibiotics: hospital admission, supportive measures and at least 48 hours of intravenous antibiotics which subsequently are switched to oral, if tolerated (for a total duration of antibiotic treatment of 10 days). II) A liberal strategy without antibiotics: admission only if needed on clinical grounds, supportive measures only. Patients are eligible for inclusion if they have a diagnosis of acute uncomplicated diverticulitis as demonstrated by radiological imaging. Only patients with stages 1a and 1b according to Hinchey's classification or "mild" diverticulitis according to the Ambrosetti criteria are included. The primary endpoint is time-to-full recovery within a 6-month follow-up period. Full recovery is defined as being discharged from the hospital, with a return to pre-illness activities, and VAS score below 4 without the use of daily pain medication. Secondary endpoints are proportion of patients who develop complicated diverticulitis requiring surgery or non-surgical intervention, morbidity, costs, health-related quality of life, readmission rate and acute diverticulitis recurrence rate. In a non-inferiority design 264 patients are needed in each study arm to detect a difference in time-to-full recovery of 5 days or more with a power of 85% and a confidence level of 95%. With an estimated one percent of patients lost to follow up, a total of 533 patients will be included.

Conclusion

A clinically relevant difference of more than 5 days in time-to-full recovery between the two treatment strategies is not expected. The liberal strategy without antibiotics and without the strict requirement for hospital admission is anticipated to be more a more cost-effective approach.

Trial registration

Trial registration number: NCT01111253