Rifaximin Delayed Release for the Prevention of Recurrent Acute Diverticulitis and Diverticular Complications.

Study Overview
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Brief Summary
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Colonic microbiota changes may play a key role in the pathogenesis of acute diverticulitis. A previous proof-of-concept study suggests that rifaximin, a low-absorbable oral antibiotic, may be beneficial for prevention of acute diverticulitis recurrence by modulating the gut microflora. The main objective of this study is to evaluate the safety and efficacy of two different doses of a delayed release formulation of rifaximin, versus placebo, for the prevention of recurrence of acute diverticulitis and diverticular complications in patients with a recent episode of acute diverticulitis.

Official Title
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Rifaximin Delayed Release (400 mg Tablet) for the Prevention of Recurrent Acute Diverticulitis and Diverticular Complications. A Phase II, Multicenter, Double-blind, Placebo-controlled, Randomized Clinical Trial

Conditions
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Diverticulitis

Intervention / Treatment
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* Drug: Rifaximin delayed released 400mg Tablet
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Men and women aged 18-80 years at screening. Female participants must be either of non-childbearing potential or of childbearing potential with a negative pregnancy test result at screening and randomization AND agreeing to use a highly effective method of contraception. A previous documented episode of diverticulitis between 30 and 180 days prior to screening. Clinical remission from acute diverticulitis at screening Key Exclusion Criteria: History of two or more acute diverticulitis episodes or history of any diverticular complication. Any documented current organic disease of the gastrointestinal tract other than diverticulosis Laboratory signs of clinically significant acute inflammation or signs/symptoms of diverticular complications. Diagnosis or history of inflammatory bowel disease (or other conditions associated with ulcerative lesions of the intestinal tract). Patients with positive Clostridium difficile toxin stool assay. Use of marketed rifaximin (or neomycin or other low-absorbable oral antibiotics) during or after the previous episode of acute diverticulitis. Severe hepatic impairment Severe kidney impairment Any other current significant health condition that in the Investigator's judgement may: i) jeopardize the patient's safe participation in the trial or ii) make unlikely the patient's completion of the study or iii) make unlikely the patient's compliance with the study procedures. History of hypersensitivity to rifaximin, rifamycin-derivatives or any of the rifaximin delayed release or placebo excipients. NOTE: Other protocol defined Inclusion/Exclusion criteria apply

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study is a phase II, multicenter, double-blind, placebo-controlled, randomized clinical trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rifaximin delayed released 800 mg b.i.d.<br>(i.e. 2 x 400 mg tablet twice a day; total daily dose: 1600 mg) for 10 consecutive days a month, for 12 months | Drug: Rifaximin delayed released 400mg Tablet<br>* Rifaximin delayed released<br>* Other names: Rifaximin-EIR;|
| Experimental: Rifaximin delayed released 400 mg b.i.d<br>(i.e. 1x400 mg tablet plus 1 placebo tablet twice a day; total daily dose: 800 mg) for 10 consecutive days a month, for 12 months | Drug: Rifaximin delayed released 400mg Tablet<br>* Rifaximin delayed released<br>* Other names: Rifaximin-EIR;Other: Placebo<br>* Placebo BID + Placebo BID<br>|
| Placebo Comparator: Placebo b.i.d.<br>(i.e. 2 x placebo tablets twice a day) for 10 consecutive days a month, for 12 months. | Other: Placebo<br>* Placebo BID + Placebo BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients with recurrence of diverticulitis and/or diverticular complications over the 12-month treatment period. |  | 12-month treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients with an acute episode of prolonged (≥24 hours) left-lower quadrant abdominal pain plus leukocytosis/elevation of CRP [Time Frame: 12-month treatment period] |  | 12-month treatment period | 
| Time to diverticulitis recurrence or complication |  | 12-month treatment period | 
| Rate of patients with diverticulitis-associated fever |  | 12-month treatment period | 
| Left-lower quadrant abdominal pain intensity |  | 12-month treatment period | 
| Left-lower quadrant abdominal pain duration |  | 12-month treatment period | 
| Number of days in a year with left-lower quadrant abdominal pain |  | 12-month treatment period | 
| Number of weeks in a year with episodes of prolonged (≥24 hours) left-lower quadrant abdominal pain |  | 12-month treatment period | 
| Number of days in a year with any abdominal pain |  | 12-month treatment period | 
| Number of weeks in a year with bloating |  | 12-month treatment period | 
| Change in bowel habits | Evaluated by Bristol Stool Scale | 12-month treatment period | 
| Rate of any hospitalization for diverticulitis |  | 12-month treatment period | 
| Rate of hospitalization for diverticulitis without surgery |  | 12-month treatment period | 
| Rate of elective surgery for diverticulitis |  | 12-month treatment period | 
| Rate of emergency surgery for diverticulitis |  | 12-month treatment period | 
| Change in Quality of Life | Evaluated by SF36 Quality of Life Questionnaire | 12-month treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent acute diverticulitis, Prevention, Diverticular complications, Rifaximin delayed release, Diverticulitis, SIBO