Diverticulitis: Antibiotics or Close Observation?

Condition(s) targeted: Diverticulitis

Intervention: Amoxicillin-clavulanate (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Official(s) and/or principal investigator(s):
Marie A Boermeester, MD, PhD, MSc, Principal Investigator, Affiliation: Academic Medical Center - University of Amsterdam

Overall contact:
Marie A Boermeester, MD, PhD, MSc, Phone: 00 31 20 566 2166, Email: M.A.Boermeester@amc.uva.nl

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.

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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Time-to-full-recovery

Secondary outcome:

Direct medical costs

Occurrence of complicated diverticulitis defined as abscess, perforation, stricture and/or fistula and need for percutaneous drainage and/or operation

Predefined side-effects of initial antibiotic treatment

Morbidity, like urinary tract infection, pneumonia, etc

Mortality

Readmission rate

Indirect medical costs

Acute diverticulitis recurrence rate

Acute diverticulitis recurrence rate

Health status

Health status

Health status

Health status

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Marie A Boermeester, MD, PhD, MSc, Phone: 00 31 20 566 2166, Email: M.A.Boermeester@amc.uva.nl

Ziekenhuisgroep Twente, Almelo, Netherlands; Recruiting
Ian F Faneyte, MD, PhD
Ian F Faneyte, MD, PhD, Principal Investigator
Susan Mollink, MD, Sub-Investigator

Flevo Hospital, Almere, Netherlands; Recruiting
M Boom, MD
M Boom, MD, Principal Investigator

Meander Hospital, Amersfoort, Netherlands; Recruiting
Esther CJ Consten, MD, PhD
Esther CJ Consten, MD, PhD, Principal Investigator
Bryan JM van de Wall, MD, Sub-Investigator

BovenIJ Hospital, Amsterdam, Netherlands; Recruiting
Rutger R Klicks, MD
Rutger J Klicks, MD, Principal Investigator
N Dhar, MD, Sub-Investigator

Academic Medical Center, Amsterdam, Netherlands; Recruiting
Marie A Boermeester, MD, PhD, MSc, Phone: 00 31 20 566 2166, Email: M.A.Boermeester@amc.uva.nl
Marie A Boermeester, MD, PhD, MSc, Principal Investigator
Lidewine Daniels, MD, Sub-Investigator

VU Medical Center, Amsterdam, Netherlands; Recruiting
Miguel A Cuesta, MD, FACS
Miguel A Cueasta, MD, FACS, Principal Investigator

Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands; Recruiting
Michael F Gerhards, MD, PhD
Michael F Gerhards, Principal Investigator
Koert FD Kuhlmann, MD, PhD, Sub-Investigator

Sint Lucas Andreas Hospital, Amsterdam, Netherlands; Recruiting
Bart C Vrouenraets, MD, PhD
Bart C Vrouenraets, Principal Investigator
Cagdas Ünlü, MD, Sub-Investigator

Slotervaart Hospital, Amsterdam, Netherlands; Recruiting
Annekatrien CT Depla, MD, PhD
Sjoerd Bruin, MD
Annekatrien CT Depla, MD, PhD, Principal Investigator
Sjoerd Bruin, MD, Principal Investigator

Gelre Hospitals, Apeldoorn, Netherlands; Recruiting
Edwin S van der Zaag, MD, PhD
Edwin S van der Zaag, MD, PhD, Principal Investigator

Rode Kruis Hospital, Beverwijk, Netherlands; Recruiting
Huibert A Cense, MD, PhD
Huibert A Cense, MD, PhD, Principal Investigator
Gerrit H de Groot, MD, PhD, Principal Investigator

Reinier de Graaf Gasthuis, Delft, Netherlands; Recruiting
Thomas M Karsten, MD, PhD
Thomas M Karsten, MD, PhD, Principal Investigator

Albert Schweitzer Hospital, Dordrecht, Netherlands; Recruiting
Joost AB van der Hoeven, MD, PhD
Joost AB van der Hoeven, MD, PhD, Principal Investigator

Kennemer Hospital, Haarlem, Netherlands; Recruiting
Hein BA Stockmann, MD, PhD
Hein BA Stockmann, MD, PhD, Principal Investigator
N de Korte, MD, Sub-Investigator
Johan P Kuyvenhoven, MD, PhD, Sub-Investigator

Ziekenhuisgroep Twente, Hengelo, Netherlands; Recruiting
Ad TP Claassen, MD, PhD
Ad TP Claassen, MD, PhD, Principal Investigator

Tergooi Hospital, Hilversum, Netherlands; Recruiting
Anna AW van Geloven, MD, PhD
Anna AW van Geloven, MD, PhD, Principal Investigator

Spaarne Hospitals, Hoofddorp, Netherlands; Recruiting
Quirinus AJ Eijsbouts, MD, PhD
Quirinus AJ Eijsbouts, MD, PhD, Principal Investigator
Philip R de Reuver, MD, PhD, Sub-Investigator

Westfries Gasthuis, Hoorn, Netherlands; Recruiting
D JA Sonneveld, Dr
D JA Sonneveld, Md, PhD, Principal Investigator
Liselotte Bouvé, MD, Sub-Investigator

Sint Antonius Hospital, Nieuwegein, Netherlands; Not yet recruiting
D Boerma, MD, PhD
D Boerma, MD, PhD, Principal Investigator

Ikazia Hospital, Rotterdam, Netherlands; Recruiting
Wouter J Vles, MD, PhD
Boudewijn R Toorenvliet, MD, PhD
Wouter J Vles, MD, PhD, Principal Investigator
Boudewijn R Toorenvliet, MD, PhD, Sub-Investigator

Sint Franciscus Gasthuis, Rotterdam, Netherlands; Recruiting
G HH Mannaerts, MD, PhD
Robert de Vos, MD, PhD
G HH Mannaerts, MD, PhD, Principal Investigator
Robert de Vos, MD, PhD, Sub-Investigator

Erasmus Medical Center, Rotterdam, Netherlands; Recruiting
J F Lange, MD, FACS
Irene Mulder, MD
J F Lange, MD, FACS, Principal Investigator
Irene Mulder, MD, Sub-Investigator

Máxima Hospital, Veldhoven, Netherlands; Recruiting
Rudolfus MH Roumen, MD, PhD
Rudolfus MH Roumen, MD, PhD, Principal Investigator

Starting date: May 2010
Last updated: July 5, 2011