Rifaximin and Placebo in the Treatment of Bowel Dysfunction After Anterior Resection for Rectal Cancer

Study Overview
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Brief Summary
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The most common long-term problems after rectal surgery are bowel problems. These problems can include needing to pass bowel movements a lot, loose or mushy stools, inability to fully clear your bowels, and/or poor control of gas and stool. The investigators believe that a major cause of these problems is too much bacteria in the bowel and treatment with antibiotic tablets will hopefully help improve these bowel problems. In order to test this idea, the Colorectal Surgery Service of Memorial Sloan Kettering Cancer Center is sponsoring a clinical trial. This trial will compare the antibiotic rifaximin and a placebo (a harmless tablet that has no effect) in the treatment of these bowel problems. Following this we will attempt to see if another antibiotic metronidazole also helps to treat these bowel problems. Both Metronidazole and rifaximin are well established drugs that have minimal side effects.

Official Title
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Randomized Control Trial Comparing Rifaximin and Placebo in the Treatment of Bowel Dysfunction After Anterior Resection for Rectal Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: Rifaximin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a history of rectal cancer treated with an anterior resection preformed at MSKCC (tumor at or below 12cm from anal verge) with restoration of bowel continuity ≥1 and ≤ 5 years. (Patients may also have had procedures to construct neo-rectums including j-pouch, coloplasty, and end to side anastomosis). Patients ≥ 21 years of age. Presence of anterior resection symptoms by patients own assessment. These symptoms may include any of the following: incomplete evacuation, clustering of bowel motions, frequency of bowel motions, unformed stool, excessive flatus, or incontinence of flatus and/or feces. Exclusion Criteria: Local recurrence of rectal cancer. Antibiotic treatment within the last 4 weeks for any condition. Pregnancy or breast feeding.

Ages Eligible for Study
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Minimum Age: 21 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pts receiving Rifaximin<br>This group will receive rifaximin 400mg bid for 4 weeks. At 1 - 24 months after completion of the phase III portion of the trial, patients will be contacted by phone and given the option of receiving metronidazole in a followup, single arm study in which all patients receive the antibiotic. Patients who wish to participate will be mailed a drug prescription for a 3 week course of metronidazole 500mgs tid as well as the BFI forms and stool diary. Pretreatment and post treatment BFI scores will be collected and analyzed for change in bowel function as was done in the initial Phase III study. | Drug: Rifaximin<br>* Pt will receive rifaximin 400mg bid for 4 weeks. Patients will at this stage on a volunteer basis be asked to submit stool samples and undertake a breath test. Patients will receive the respective treatment for four weeks. Following cessation of treatment all patients will be assessed using the BFI and respective patients will have repeat stool sampling and breath testing. Patients will then have these tests repeated 4 weeks later. This corresponds to 8 weeks after the start of the trial. For those patients not undertaking stool and breath testing, they will be reminded by phone, mail or email to fill out the BFI. Before and during the trial patients will be asked to fill out a weekly stool diary to evaluate trends on bowel function.<br>* Other names: was done in the initial Phase III study.;|
| Placebo Comparator: Pts receiving placebo<br>This group will receive a placebo bid for 4 weeks. At 1 - 24 months after completion of the phase III portion of the trial, patients will be contacted by phone and given the option of receiving metronidazole in a followup, single arm study in which all patients receive the antibiotic. Patients who wish to participate will be mailed a drug prescription for a 3 week course of metronidazole 500mgs tid as well as the BFI forms and stool diary. Pretreatment and post treatment BFI scores will be collected and analyzed for change in bowel function as was done in the initial Phase III study. | Drug: Placebo<br>* Pt will receive placebo bid for 4 weeks. Patients will at this stage on a volunteer basis be asked to submit stool samples and undertake a breath test. Patients will receive the respective treatment for four weeks. Following cessation of treatment all patients will be assessed using the BFI and respective patients will have repeat stool sampling and breath testing. Patients will then have these tests repeated 4 weeks later. This corresponds to 8 weeks after the start of the trial. For those patients not undertaking stool and breath testing, they will be reminded by phone, mail or email to fill out the BFI. Before and during the trial patients will be asked to fill out a weekly stool diary to evaluate trends on bowel function.<br>* Other names: Phase III study.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the efficacy of rifaximin and placebo in the treatment of bowel dysfunction as measured by MSKCC Bowel Function Instrument (BFI score) in patients following Anterior Resection (AR) or Sphincter Preserving Surgery (SPS) for rectal cancer. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine if reduction in intestinal bacterial quantity correlates with improvement in bowel symptoms (BFI score). |  | 1 year | 
| To explore the bacterial composition of stool before and after antibiotic treatment. |  | 1 year | 
| To identify dynamic changes in bowel function during and after antibiotic treatment using a bowel function log. |  | 1 year | 
| efficacy of metronidazole | in the treatment of bowel dysfunction as measured by the MSKCC BFI in patients following AR or SPS for rectal cancer for patients who have no improvement following treatment with rifaximin or placebo. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal, colon, PLACEBO, RIFAXIMIN, metronidazole, 11-045