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

Study Overview
=================
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.

Detailed 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.

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

Conditions
-----------------
Acute Diverticulitis

Intervention / Treatment
-----------------
* Drug: Ibuprofen
* Drug: Acetaminophen
* Drug: Amoxicillin/clavulanic acid


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Symptomatic treatment with NSAID<br>1 g/8 h acetaminophen alternating with 600 mg/8 h ibuprofen | Drug: Ibuprofen<br>* 600 mg/8hours<br>Drug: Acetaminophen<br>* 1 g/8 hours<br>* Other names: Paracetamol;|
| Active Comparator: Antibiotic+symptomatic treatment with NSAID<br>875/125mg /8h amoxicillin/clavulanic acid and symptomatic treatment with 1 g/8 h acetaminophen alternating with 600 mg/8 h ibuprofen | Drug: Ibuprofen<br>* 600 mg/8hours<br>Drug: Acetaminophen<br>* 1 g/8 hours<br>* Other names: Paracetamol;Drug: Amoxicillin/clavulanic acid<br>* 875mg/125mg/8 hours<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reconsultation ratio | The analysis of the differences between groups, in case there are, in relation to number and reason for reconsultation | 3 months | 
| Reason for reconsultation | The analysis of the differences between groups, in case there are, in relation to number and reason for reconsultation | 3 months | 
| 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 | 
| 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 | 
| Complications | Description of the complications in both groups (perforation, abscess) and its treatment (percutaneous drainage, emergency surgery, broad spectrum antibiotics) | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute diverticulitis, Antibiotic, Outpatient treatment