Clinical trial NCT01111253: Diverticulitis: Antibiotics or Close Observation?
Official title: DIABOLO Trial: A Multicenter Randomized Clinical Trial Investigating the Cost-effectiveness of Treatment Strategies With or Without Antibiotics for Uncomplicated Acute Diverticulitis.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Diverticulitis
Keywords: multicenter randomized, open label, clinical trial
acute uncomplicated (mild) diverticulitis
treatment strategies
management of diverticulitis
antibiotics
observation and supportive care
cost analysis
economic evaluation
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Dutch Digestive Diseases Foundation
First posted: 2010-04-27
Enrollment: 533
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Time-to-full-recovery
timeFrame: 6 months follow-up
Secondary outcomes:
measure: Direct medical costs
timeFrame: 6 months follow-up
measure: Occurrence of complicated diverticulitis defined as abscess, perforation, stricture and/or fistula and need for percutaneous drainage and/or operation
timeFrame: 24 months follow-up
measure: Predefined side-effects of initial antibiotic treatment
timeFrame: 24 months follow-up
measure: Morbidity, like urinary tract infection, pneumonia, etc
timeFrame: 24 months follow-up
measure: Mortality
timeFrame: 24 months follow-up
measure: Readmission rate
timeFrame: 6 months follow-up
measure: Indirect medical costs
timeFrame: 6 months follow-up
measure: Acute diverticulitis recurrence rate
timeFrame: 12 months follow-up
measure: Acute diverticulitis recurrence rate
timeFrame: 24 months follow-up
measure: Health status
timeFrame: 3 months follow-up
measure: Health status
timeFrame: 6 months follow-up
measure: Health status
timeFrame: 12 months follow-up
measure: Health status
timeFrame: 24 months follow-up
Other outcomes:
Locations:
city: Almelo
country: Netherlands
facility: Ziekenhuisgroep Twente
city: Almere
country: Netherlands
facility: Flevo Hospital
city: Amersfoort
country: Netherlands
facility: Meander Hospital
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Amsterdam
country: Netherlands
facility: BovenIJ Hospital
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Amsterdam
country: Netherlands
facility: Sint Lucas Andreas Hospital
city: Amsterdam
country: Netherlands
facility: Slotervaart Hospital
city: Amsterdam
country: Netherlands
facility: VU Medical Center
city: Apeldoorn
country: Netherlands
facility: Gelre Hospitals
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
city: Beverwijk
country: Netherlands
facility: Rode Kruis Hospital
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Hospital
city: Haarlem
country: Netherlands
facility: Kennemer Hospital
city: Hengelo
country: Netherlands
facility: Ziekenhuisgroep Twente
city: Hilversum
country: Netherlands
facility: Tergooi Hospital
city: Hoofddorp
country: Netherlands
facility: Spaarne Hospitals
city: Hoorn
country: Netherlands
facility: Westfries Gasthuis
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Rotterdam
country: Netherlands
facility: Ikazia Hospital
city: Rotterdam
country: Netherlands
facility: Sint Franciscus Gasthuis
city: Veldhoven
country: Netherlands
facility: Máxima Hospital
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Marie A Boermeester, MD, PhD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Korte N, Unlu 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.
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.
citation: 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.
citation: Unlu 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.
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. Dutch.
citation: Unlu 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.
citation: Daniels L, Unlu C, de Korte N, van Dieren S, Stockmann HB, Vrouenraets BC, Consten EC, van der Hoeven JA, Eijsbouts QA, Faneyte IF, Bemelman WA, Dijkgraaf MG, Boermeester MA; Dutch Diverticular Disease (3D) Collaborative Study Group. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017 Jan;104(1):52-61. doi: 10.1002/bjs.10309. Epub 2016 Sep 30.