NCT01111253

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
533

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started May 2010

Longer than P75 for phase_4

Geographic Reach
1 country

24 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 22, 2010

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 27, 2010

Completed
4 days until next milestone

Study Start

First participant enrolled

May 1, 2010

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2013

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2014

Completed
Last Updated

October 29, 2012

Status Verified

October 1, 2012

Enrollment Period

2.9 years

First QC Date

April 22, 2010

Last Update Submit

October 26, 2012

Conditions

Keywords

multicenter randomized, open label, clinical trialacute uncomplicated (mild) diverticulitistreatment strategiesmanagement of diverticulitisantibioticsobservation and supportive carecost analysiseconomic evaluation

Outcome Measures

Primary Outcomes (1)

  • Time-to-full-recovery

    6 months follow-up

Secondary Outcomes (13)

  • Direct medical costs

    6 months follow-up

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

    24 months follow-up

  • Predefined side-effects of initial antibiotic treatment

    24 months follow-up

  • Morbidity, like urinary tract infection, pneumonia, etc

    24 months follow-up

  • Mortality

    24 months follow-up

  • +8 more secondary outcomes

Study Arms (2)

Conservative strategy with antibiotics

ACTIVE COMPARATOR

* 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

Liberal strategy without antibiotics

NO INTERVENTION

* 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)

Interventions

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.

Also known as: Augmentin.
Conservative strategy with antibiotics

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Only left-sided uncomplicated (mild) acute diverticulitis;
  • All patients with informed consent.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

Ziekenhuisgroep Twente

Almelo, Netherlands

Location

Flevo Hospital

Almere Stad, Netherlands

Location

Meander Hospital

Amersfoort, Netherlands

Location

Academic Medical Center

Amsterdam, Netherlands

Location

BovenIJ Hospital

Amsterdam, Netherlands

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, Netherlands

Location

Sint Lucas Andreas Hospital

Amsterdam, Netherlands

Location

Slotervaart Hospital

Amsterdam, Netherlands

Location

VU Medical Center

Amsterdam, Netherlands

Location

Gelre Hospitals

Apeldoorn, Netherlands

Location

Rijnstate Hospital

Arnhem, Netherlands

Location

Rode Kruis Hospital

Beverwijk, Netherlands

Location

Reinier de Graaf Gasthuis

Delft, Netherlands

Location

Albert Schweitzer Hospital

Dordrecht, Netherlands

Location

Kennemer Hospital

Haarlem, Netherlands

Location

Ziekenhuisgroep Twente

Hengelo, Netherlands

Location

Tergooi Hospital

Hilversum, Netherlands

Location

Spaarne Hospitals

Hoofddorp, Netherlands

Location

Westfries Gasthuis

Hoorn, Netherlands

Location

Sint Antonius Hospital

Nieuwegein, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

Ikazia Hospital

Rotterdam, Netherlands

Location

Sint Franciscus Gasthuis

Rotterdam, Netherlands

Location

Máxima Hospital

Veldhoven, Netherlands

Location

Related Publications (7)

  • 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.

    PMID: 21523694BACKGROUND
  • 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.

    PMID: 21689302BACKGROUND
  • 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.

    PMID: 21819518BACKGROUND
  • 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.

    PMID: 20646266BACKGROUND
  • 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.

    PMID: 19857313BACKGROUND
  • 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.

    PMID: 21922199BACKGROUND
  • 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.

MeSH Terms

Conditions

DiverticulitisLymphoma, Follicular

Interventions

Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Diverticular DiseasesGastroenteritisGastrointestinal DiseasesDigestive System DiseasesLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Clavulanic AcidClavulanic Acidsbeta-LactamsLactamsAmidesOrganic ChemicalsAmoxicillinAmpicillinPenicillin GPenicillinsSulfur CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsDrug CombinationsPharmaceutical Preparations

Study Officials

  • Marie A Boermeester, MD, PhD, MSc

    Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

April 22, 2010

First Posted

April 27, 2010

Study Start

May 1, 2010

Primary Completion

April 1, 2013

Study Completion

October 1, 2014

Last Updated

October 29, 2012

Record last verified: 2012-10

Locations