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

Acute Diverticulitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02785549
• Other study ID #: CIR-DISA-2016
• Secondary ID: 2016-001596-75
• Status: Completed
• Phase: Phase 4
• Start date: November 2016
• Est. completion date: April 1, 2020

Study information

• Verified date: May 2020
• Source: Corporacion Parc Tauli
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

In the last years, traditional pathologic mechanisms of acute diverticulitis are being questioned and replaced by more scientifically grounded hypotheses that strongly postulate an inflammatory origin. Local pro-inflammatory cytokines, microbiota shifts, disturbed neurological intestinal signalling due to alterations in colonic neuropeptides and abnormal colonic motility are all being proposed as potential etiologic factors. Recent publications, therefore, call into question the benefits of antibiotic treatment or episodes of acute diverticulitis, especially for mild episodes. Furthermore, recent international guidelines endorse this stance in their recommendations. Moreover, recent studies provide evidence regarding the security of treating patients with mild acute diverticulitis as outpatients.

The investigators think that outpatient treatment without antibiotic for mild acute diverticulitis is not-inferior to traditional treatment with antibiotic, measuring the efficacy with readmission ratio. For this reason we have designed a multicentric, randomised, prospective study.

All patients seen in the emergency department with clinical signs of acute diverticulitis (left iliac fossa abdominal pain, peritoneal irritation signs and/or leucocytosis) will undergo an abdominal computed tomography to confirm the diagnosis and grade the disease according to severity using the modified Neff (mNeff) classification. Those with mild acute diverticulitis (grade 0), 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.

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

Secondary goals include the analysis of the differences between groups, in case there are, in relation to number and reason for reconsultation, reason for readmission (bad symptoms control, radiologic progression, analysis worsening), pain control (analogic visual scale), recuperation after the acute episode, complication rate and their treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 480
• Est. completion date: April 1, 2020
• Est. primary completion date: January 12, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Acute Diverticulitis
• Diverticulitis

Intervention

Drug:
• Ibuprofen
600 mg/8hours
• Acetaminophen
1 g/8 hours
• Amoxicillin/clavulanic acid
875mg/125mg/8 hours

Locations

Country	Name	City	State
Spain	Corporació Sanitària Parc Taulí	Sabadell	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Corporacion Parc Tauli

Country where clinical trial is conducted

Spain, 

References & Publications (19)

Alonso S, Pera M, Parés 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. — View Citation

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

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. Review. — View Citation

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. — View Citation

Brochmann ND, Schultz JK, Jakobsen GS, Øresland 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. — View Citation

Chabok A, Påhlman 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. — View Citation

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. — View Citation

Daniels L, Budding AE, de Korte N, Eck A, Bogaards JA, Stockmann HB, Consten EC, Savelkoul PH, Boermeester MA. Fecal microbiome analysis as a diagnostic test for diverticulitis. Eur J Clin Microbiol Infect Dis. 2014 Nov;33(11):1927-36. doi: 10.1007/s10096-014-2162-3. Epub 2014 Jun 4. — View Citation

Espín F, Rofes L, Ortega O, Clavé P, Gallego D. Nitrergic neuro-muscular transmission is up-regulated in patients with diverticulosis. Neurogastroenterol Motil. 2014 Oct;26(10):1458-68. doi: 10.1111/nmo.12407. Epub 2014 Aug 11. — View Citation

Estrada Ferrer O, Ruiz Edo N, Hidalgo Grau LA, Abadal Prades M, Del Bas Rubia M, Garcia Torralbo EM, Heredia Budo A, Suñol Sala X. Selective non-antibiotic treatment in sigmoid diverticulitis: is it time to change the traditional approach? Tech Coloproctol. 2016 May;20(5):309-315. doi: 10.1007/s10151-016-1464-0. Epub 2016 Apr 6. — View Citation

Gargallo Puyuelo CJ, Sopeña 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. Review. — View Citation

Humes DJ, Simpson J, Smith J, Sutton P, Zaitoun A, Bush D, Bennett A, Scholefield JH, Spiller RC. Visceral hypersensitivity in symptomatic diverticular disease and the role of neuropeptides and low grade inflammation. Neurogastroenterol Motil. 2012 Apr;24(4):318-e163. doi: 10.1111/j.1365-2982.2011.01863.x. Epub 2012 Jan 25. — View Citation

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. — View Citation

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. Review. — View Citation

Mäkelä 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. — View Citation

Mäkelä 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. — View Citation

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. — View Citation

Strate LL, Modi R, Cohen E, Spiegel BM. Diverticular disease as a chronic illness: evolving epidemiologic and clinical insights. Am J Gastroenterol. 2012 Oct;107(10):1486-93. doi: 10.1038/ajg.2012.194. Epub 2012 Jul 10. Review. — View Citation

Unlü 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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Reconsultation ratio	The analysis of the differences between groups, in case there are, in relation to number and reason for reconsultation	3 months
Secondary	Reason for reconsultation	The analysis of the differences between groups, in case there are, in relation to number and reason for reconsultation	3 months
Secondary	Reason for readmission	The analysis of the differences between groups, in case there are, in relation to reason for readmission (bad symptoms control, radiologic progression, analysis worsening)	3 months
Secondary	Pain control	The analysis of the differences between groups, in case there are, in relation to pain control (analogic visual scale), during follow-up.	48 hours, 7 days, 1 month, 3 months
Secondary	Complications	Description of the complications in both groups (perforation, abscess) and its treatment (percutaneous drainage, emergency surgery, broad spectrum antibiotics)	3 months