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Diverticulitis: Antibiotics or Close Observation? (DIABOLO)

Primary Purpose

Diverticulitis

Status
Unknown status
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Amoxicillin-clavulanate
Sponsored by
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diverticulitis focused on measuring multicenter randomized, open label, clinical trial, acute uncomplicated (mild) diverticulitis, treatment strategies, management of diverticulitis, antibiotics, observation and supportive care, cost analysis, economic evaluation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Ziekenhuisgroep Twente
  • Flevo Hospital
  • Meander Hospital
  • Academic Medical Center
  • BovenIJ Hospital
  • Onze Lieve Vrouwe Gasthuis
  • Sint Lucas Andreas Hospital
  • Slotervaart Hospital
  • VU Medical Center
  • Gelre Hospitals
  • Rijnstate Hospital
  • Rode Kruis Hospital
  • Reinier de Graaf Gasthuis
  • Albert Schweitzer Hospital
  • Kennemer Hospital
  • Ziekenhuisgroep Twente
  • Tergooi Hospital
  • Spaarne Hospitals
  • Westfries Gasthuis
  • Sint Antonius Hospital
  • Erasmus Medical Center
  • Ikazia Hospital
  • Sint Franciscus Gasthuis
  • Máxima Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Conservative strategy with antibiotics

Liberal strategy without antibiotics

Arm Description

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

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)

Outcomes

Primary Outcome Measures

Time-to-full-recovery

Secondary Outcome Measures

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
e.g. antibiotic resistance/sensitivity pattern, allergy
Morbidity, like urinary tract infection, pneumonia, etc
Mortality
Readmission rate
Indirect medical costs
Acute diverticulitis recurrence rate
Acute diverticulitis recurrence rate
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))
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))
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))
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))

Full Information

First Posted
April 22, 2010
Last Updated
October 26, 2012
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development, Dutch Digestive Diseases Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01111253
Brief Title
Diverticulitis: Antibiotics or Close Observation?
Acronym
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.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Unknown status
Study Start Date
May 2010 (undefined)
Primary Completion Date
April 2013 (Anticipated)
Study Completion Date
October 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development, Dutch Digestive Diseases Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
533 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Conservative strategy with antibiotics
Arm Type
Active Comparator
Arm Description
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
Arm Title
Liberal strategy without antibiotics
Arm Type
No Intervention
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Amoxicillin-clavulanate
Other Intervention Name(s)
Augmentin.
Intervention Description
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.
Primary Outcome Measure Information:
Title
Time-to-full-recovery
Time Frame
6 months follow-up
Secondary Outcome Measure Information:
Title
Direct medical costs
Time Frame
6 months follow-up
Title
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
Title
Predefined side-effects of initial antibiotic treatment
Description
e.g. antibiotic resistance/sensitivity pattern, allergy
Time Frame
24 months follow-up
Title
Morbidity, like urinary tract infection, pneumonia, etc
Time Frame
24 months follow-up
Title
Mortality
Time Frame
24 months follow-up
Title
Readmission rate
Time Frame
6 months follow-up
Title
Indirect medical costs
Time Frame
6 months follow-up
Title
Acute diverticulitis recurrence rate
Time Frame
12 months follow-up
Title
Acute diverticulitis recurrence rate
Time Frame
24 months follow-up
Title
Health status
Description
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))
Time Frame
3 months follow-up
Title
Health status
Description
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))
Time Frame
6 months follow-up
Title
Health status
Description
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))
Time Frame
12 months follow-up
Title
Health status
Description
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))
Time Frame
24 months follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marie A Boermeester, MD, PhD, MSc
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ziekenhuisgroep Twente
City
Almelo
Country
Netherlands
Facility Name
Flevo Hospital
City
Almere
Country
Netherlands
Facility Name
Meander Hospital
City
Amersfoort
Country
Netherlands
Facility Name
Academic Medical Center
City
Amsterdam
Country
Netherlands
Facility Name
BovenIJ Hospital
City
Amsterdam
Country
Netherlands
Facility Name
Onze Lieve Vrouwe Gasthuis
City
Amsterdam
Country
Netherlands
Facility Name
Sint Lucas Andreas Hospital
City
Amsterdam
Country
Netherlands
Facility Name
Slotervaart Hospital
City
Amsterdam
Country
Netherlands
Facility Name
VU Medical Center
City
Amsterdam
Country
Netherlands
Facility Name
Gelre Hospitals
City
Apeldoorn
Country
Netherlands
Facility Name
Rijnstate Hospital
City
Arnhem
Country
Netherlands
Facility Name
Rode Kruis Hospital
City
Beverwijk
Country
Netherlands
Facility Name
Reinier de Graaf Gasthuis
City
Delft
Country
Netherlands
Facility Name
Albert Schweitzer Hospital
City
Dordrecht
Country
Netherlands
Facility Name
Kennemer Hospital
City
Haarlem
Country
Netherlands
Facility Name
Ziekenhuisgroep Twente
City
Hengelo
Country
Netherlands
Facility Name
Tergooi Hospital
City
Hilversum
Country
Netherlands
Facility Name
Spaarne Hospitals
City
Hoofddorp
Country
Netherlands
Facility Name
Westfries Gasthuis
City
Hoorn
Country
Netherlands
Facility Name
Sint Antonius Hospital
City
Nieuwegein
Country
Netherlands
Facility Name
Erasmus Medical Center
City
Rotterdam
Country
Netherlands
Facility Name
Ikazia Hospital
City
Rotterdam
Country
Netherlands
Facility Name
Sint Franciscus Gasthuis
City
Rotterdam
Country
Netherlands
Facility Name
Máxima Hospital
City
Veldhoven
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
21523694
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.
Results Reference
background
PubMed Identifier
21689302
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.
Results Reference
background
PubMed Identifier
21819518
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.
Results Reference
background
PubMed Identifier
20646266
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.
Results Reference
background
PubMed Identifier
19857313
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.
Results Reference
background
PubMed Identifier
21922199
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.
Results Reference
background
PubMed Identifier
27686365
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.
Results Reference
derived

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Diverticulitis: Antibiotics or Close Observation?

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