Randomized Clinical Trial to Compare the Treatment of Mild Acute Diverticulitis With or Without Antibiotics

NCT02785549 | Completed Phase 4

• 2 other identifiers: CIR-DISA-20162016-001596-75
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with mild acute diverticulitis (modified Neff 0 grade), following the inclusion criteria and giving informed consent, will be included in the study protocol and will be randomly assigned to one of the treatment arms: symptomatic treatment with NSAID plus antibiotic vs symptomatic treatment with NSAID only. They will be followed-up at 48 hours, 7 days, 30 days and 3 months from the onset of the episode.

Conditions

Acute Diverticulitis

Keywords

Acute diverticulitis; Antibiotic; Outpatient treatment

Outcome Measures

Primary Outcomes (1)

• Readmission ratio

  Primary outcome is to determine if, in mild acute diverticulitis, the treatment without antibiotic is not-inferior to the traditional treatment with antibiotic considering readmission ratio.

  3 months

Secondary Outcomes (5)

• Reconsultation ratio

  3 months

• Reason for reconsultation

  3 months

• Reason for readmission

  3 months

• Pain control

  48 hours, 7 days, 1 month, 3 months

• Complications

  3 months

Study Arms (2)

Symptomatic treatment with NSAID

EXPERIMENTAL

1 g/8 h acetaminophen alternating with 600 mg/8 h ibuprofen

Drug: Ibuprofen; Drug: Acetaminophen

Antibiotic+symptomatic treatment with NSAID

ACTIVE COMPARATOR

875/125mg /8h amoxicillin/clavulanic acid and symptomatic treatment with 1 g/8 h acetaminophen alternating with 600 mg/8 h ibuprofen

Drug: Ibuprofen; Drug: Acetaminophen; Drug: Amoxicillin/clavulanic acid

Interventions

Ibuprofen DRUG

600 mg/8hours

Antibiotic+symptomatic treatment with NSAID; Symptomatic treatment with NSAID

Acetaminophen DRUG

1 g/8 hours

Also known as: Paracetamol

Antibiotic+symptomatic treatment with NSAID; Symptomatic treatment with NSAID

Amoxicillin/clavulanic acid DRUG

875mg/125mg/8 hours

Antibiotic+symptomatic treatment with NSAID

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient's written informed consent. Adequate cognitive capacity.
• Adequate family support
• No acute diverticulitis episode in the last 3 months
• mNeff 0 acute diverticulitis (abdominal computed tomography scan)
• No antibiotic treatment in the last 2 weeks
• Immunocompetence\*
• No significant comorbidities\*\*
• Good oral tolerance
• Good symptom control
• Maximum one of the following SIRS criteria (\* T\>38 ºC or \<36ºC, L\>12,000 or \<4000/uL, HR\>90 bpm, RR\<20 rpm) or CRP\>15 mg/dL

You may not qualify if:

• Women in pregnancy or breastfeeding
• Age \<18 years or \> 80 years.
• Absence of the patient's written informed consent. Inadequate cognitive capacity.
• Inadequate family support
• Acute diverticulitis episode in the last 3 months
• Moderate acute diverticulitis (mNeff grade I or upper)
• Antibiotic treatment in the last 2 weeks
• Inflammatory bowel disease
• Immunodepression\*
• Presence of significant comorbidities\*\*
• Bad oral tolerance
• Poor symptom control
• More than one of the following SIRS criteria (\* T\>38 ºC or \<36ºC, L\>12,000 or \<4000/uL, HR\>90 bpm, RR\<20 rpm) or CRP\>15 mg/dL
• (\*) Immunocompetence is the absence and immunodepression is the presence of any of the following: active neoplastic disease/hematologic malignancy/HIV with low CD4+ count/long-term corticosteroid treatment/immunosuppressant therapy/transplant/splenectomy/genetic immunodeficiency.
• (\*\*) We consider significant comorbidities any of the following: poorly controlled diabetes mellitus (HbA1\>7mg/dl), cardiologic event in the last 3 months, decompensation of hepatopathy in the last 3 months, renal chronic insufficiency in dialysis programme.

Sponsors & Collaborators

• Corporacion Parc Tauli: lead

Study Sites (1)

Corporació Sanitària Parc Taulí

Sabadell, Barcelona, 08208, Spain

Location

Related Publications (21)

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• Chabok A, Pahlman L, Hjern F, Haapaniemi S, Smedh K; AVOD Study Group. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012 Apr;99(4):532-9. doi: 10.1002/bjs.8688. Epub 2012 Jan 30.

  PMID: 22290281 BACKGROUND

• Isacson D, Thorisson A, Andreasson K, Nikberg M, Smedh K, Chabok A. Erratum to: Outpatient, non-antibiotic management in acute uncomplicated diverticulitis: a prospective study. Int J Colorectal Dis. 2015 Sep;30(9):1235. doi: 10.1007/s00384-015-2284-9. No abstract available.

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  PMID: 27053254 BACKGROUND

• Brochmann ND, Schultz JK, Jakobsen GS, Oresland T. Management of acute uncomplicated diverticulitis without antibiotics: a single-centre cohort study. Colorectal Dis. 2016 Nov;18(11):1101-1107. doi: 10.1111/codi.13355.

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• 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: 20646266 BACKGROUND

• Andersen JC, Bundgaard L, Elbrond H, Laurberg S, Walker LR, Stovring J; Danish Surgical Society. Danish national guidelines for treatment of diverticular disease. Dan Med J. 2012 May;59(5):C4453.

  PMID: 22549495 BACKGROUND

• Andeweg CS, Mulder IM, Felt-Bersma RJ, Verbon A, van der Wilt GJ, van Goor H, Lange JF, Stoker J, Boermeester MA, Bleichrodt RP; Netherlands Society of Surgery; Working group from Netherlands Societies of Internal Medicine, Gastroenterologists, Radiology, Health echnology Assessment and Dieticians. Guidelines of diagnostics and treatment of acute left-sided colonic diverticulitis. Dig Surg. 2013;30(4-6):278-92. doi: 10.1159/000354035. Epub 2013 Aug 20.

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• Cuomo R, Barbara G, Pace F, Annese V, Bassotti G, Binda GA, Casetti T, Colecchia A, Festi D, Fiocca R, Laghi A, Maconi G, Nascimbeni R, Scarpignato C, Villanacci V, Annibale B. Italian consensus conference for colonic diverticulosis and diverticular disease. United European Gastroenterol J. 2014 Oct;2(5):413-42. doi: 10.1177/2050640614547068.

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• Kruis W, Germer CT, Leifeld L; German Society for Gastroenterology, Digestive and Metabolic Diseases and The German Society for General and Visceral Surgery. Diverticular disease: guidelines of the german society for gastroenterology, digestive and metabolic diseases and the german society for general and visceral surgery. Digestion. 2014;90(3):190-207. doi: 10.1159/000367625. Epub 2014 Nov 19.

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• Mora Lopez L, Serra Pla S, Serra-Aracil X, Ballesteros E, Navarro S. Application of a modified Neff classification to patients with uncomplicated diverticulitis. Colorectal Dis. 2013 Nov;15(11):1442-7. doi: 10.1111/codi.12449.

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• Alonso S, Pera M, Pares D, Pascual M, Gil MJ, Courtier R, Grande L. Outpatient treatment of patients with uncomplicated acute diverticulitis. Colorectal Dis. 2010 Oct;12(10 Online):e278-82. doi: 10.1111/j.1463-1318.2009.02122.x.

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• Biondo S, Golda T, Kreisler E, Espin E, Vallribera F, Oteiza F, Codina-Cazador A, Pujadas M, Flor B. Outpatient versus hospitalization management for uncomplicated diverticulitis: a prospective, multicenter randomized clinical trial (DIVER Trial). Ann Surg. 2014 Jan;259(1):38-44. doi: 10.1097/SLA.0b013e3182965a11.

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• Gargallo Puyuelo CJ, Sopena F, Lanas Arbeloa A. Colonic diverticular disease. Treatment and prevention. Gastroenterol Hepatol. 2015 Dec;38(10):590-9. doi: 10.1016/j.gastrohep.2015.03.010. Epub 2015 May 12.

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• Makela JT, Klintrup K, Rautio T. The role of low CRP values in the prediction of the development of acute diverticulitis. Int J Colorectal Dis. 2016 Jan;31(1):23-7. doi: 10.1007/s00384-015-2410-8. Epub 2015 Oct 31.

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• Makela JT, Klintrup K, Takala H, Rautio T. The role of C-reactive protein in prediction of the severity of acute diverticulitis in an emergency unit. Scand J Gastroenterol. 2015 May;50(5):536-41. doi: 10.3109/00365521.2014.999350. Epub 2015 Feb 9.

  PMID: 25665622 BACKGROUND

• Mora-Lopez L, Ruiz-Edo N, Estrada-Ferrer O, Pinana-Campon ML, Labro-Ciurans M, Escuder-Perez J, Sales-Mallafre R, Rebasa-Cladera P, Navarro-Soto S, Serra-Aracil X; DINAMO-study Group. Efficacy and Safety of Nonantibiotic Outpatient Treatment in Mild Acute Diverticulitis (DINAMO-study): A Multicentre, Randomised, Open-label, Noninferiority Trial. Ann Surg. 2021 Nov 1;274(5):e435-e442. doi: 10.1097/SLA.0000000000005031.

  PMID: 34183510 DERIVED

• Mora Lopez L, Ruiz-Edo N, Serra Pla S, Pallisera Llovera A, Navarro Soto S, Serra-Aracil X; Diverticulitis Study Group. Multicentre, controlled, randomized clinical trial to compare the efficacy and safety of ambulatory treatment of mild acute diverticulitis without antibiotics with the standard treatment with antibiotics. Int J Colorectal Dis. 2017 Oct;32(10):1509-1516. doi: 10.1007/s00384-017-2879-4. Epub 2017 Aug 14.

  PMID: 28808771 DERIVED

MeSH Terms

Interventions

Ibuprofen; Acetaminophen; Amoxicillin-Potassium Clavulanate Combination

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Neus Ruiz, MD

  Corporacion Parc Tauli

  PRINCIPAL INVESTIGATOR

• Laura Mora, MD PhD

  Corporacion Parc Tauli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 25, 2016
• First Posted: May 30, 2016
• Study Start: November 1, 2016
• Primary Completion: January 12, 2020
• Study Completion: April 1, 2020
• Last Updated: May 14, 2020

Record last verified: 2020-05

Locations

ES (1)