Diverticulitis: Antibiotics or Close Observation? (DIABOLO)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
Maag Lever Darm Stichting (MLDS)
Information provided by (Responsible Party):
M.A. Boermeester, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01111253
First received: April 22, 2010
Last updated: October 26, 2012
Last verified: October 2012
  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.

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • Time-to-full-recovery [ Time Frame: 6 months follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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
  • Hospital admission
  • Intravenous fluids and at least 48 hours of intravenous antibiotics and subsequently switch to oral antibiotics if tolerated (otherwise continuation i.v.) to complete a full 10-day treatment duration
  • Adequate pain relief
  • Oral intake as tolerated
  • Daily monitoring
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
  • Admission only if discharge criteria are not met
  • No initial antibiotics
  • Intravenous fluids only for those not tolerating oral liquids
  • Adequate pain relief
  • Oral intake as tolerated
  • Daily monitoring when admitted to the hospital
  • Self-monitoring at home (Patient diary with temperature and VAS pain score until full recovery)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01111253

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
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ZonMw: The Netherlands Organisation for Health Research and Development
Maag Lever Darm Stichting (MLDS)
Investigators
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
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014