Rifaximin for Pouchitis

Recruiting at 1 trial location

Overseen By Mikki Sandridge

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of North Carolina, Chapel Hill

Must be taking: Rifaximin

Must not be taking: P-gp inhibitors

Disqualifiers: Crohn's, Hepatitis B, C, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether rifaximin, an antibiotic, can prevent the recurrence of pouchitis after the first episode has been treated. Pouchitis occurs when the pouch created during ulcerative colitis surgery becomes inflamed. Participants will take rifaximin daily for a year to determine if it prevents inflammation from returning and to monitor for any unexpected side effects. Individuals who have undergone ulcerative colitis surgery and recently experienced their first bout of pouchitis may be suitable for this study. As a Phase 4 trial, this research aims to understand how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you need long-term antibiotic therapy or are using certain medications like p-glycoprotein inhibitors. It's best to discuss your specific medications with the trial team.

What is the safety track record for rifaximin?

Research has shown that rifaximin is generally safe for use. One study found that 65% of patients with antibiotic-dependent pouchitis used rifaximin without problems for at least three months. Another study reported that rifaximin was well tolerated for up to 24 months, with very few discontinuations. Rifaximin is already approved for treating conditions like irritable bowel syndrome with diarrhea and certain liver issues, indicating its safety for these uses. Overall, rifaximin appears well tolerated, with few experiencing side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Rifaximin is unique because it's an antibiotic that targets the gut with minimal absorption into the bloodstream, making it potentially safer for long-term use. Unlike traditional treatments for pouchitis, which often involve systemic antibiotics or steroids with broader effects, rifaximin acts locally in the intestines. Researchers are excited because it offers a targeted approach, reducing the risk of systemic side effects while potentially providing effective relief for chronic pouchitis symptoms over an extended period.

What evidence suggests that rifaximin might be an effective treatment for preventing recurrent pouchitis?

Research has shown that rifaximin, an antibiotic, can help manage pouchitis, which is inflammation in a surgically created intestinal pouch after surgery for ulcerative colitis. One study found that 65% of patients taking rifaximin kept their symptoms under control for at least three months. Another study found that 25% of patients taking rifaximin had no symptoms, while none in the placebo group did. These findings suggest that rifaximin might help prevent pouchitis from returning. The evidence supports rifaximin as a promising option for managing this condition, making it worth considering for those seeking effective treatments. Participants in this trial will receive 550 mg of rifaximin twice a day for 365 days. ^{3 6 7 8 9}

Who Is on the Research Team?

Edward Barnes, MD, MPH

Principal Investigator

University of North Carolina

Are You a Good Fit for This Trial?

This trial is for individuals who have had a colectomy for ulcerative colitis and are experiencing their first episode of pouchitis, which is inflammation of the J-pouch. Participants will be those looking to prevent recurrent inflammation after initial treatment.

Inclusion Criteria

I have given my consent for all study-related procedures.

I have a history of ulcerative colitis and have undergone specific surgeries for it.

I was diagnosed with pouchitis within a year after my ileostomy reversal surgery.

Exclusion Criteria

Known hypersensitivity to rifaximin or its metabolites

I need long-term antibiotics, like doxycycline, for a condition.

I have severe liver problems (Child-Pugh Class C).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 550 mg Rifaximin twice a day for 365 days to prevent recurrent pouchitis

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Rifaximin

Trial Overview The study tests if taking Rifaximin (an antibiotic) daily for one year can prevent recurring pouchitis after an initial episode. All participants in this study will receive Rifaximin with the aim to assess its effectiveness and adherence over a year.

How Is the Trial Designed?

Group I: All Participants Experimental Treatment 1 Intervention

550 mg Rifaximin (Xifaxan) twice a day x 365 days

Rifaximin is already approved in United States, Canada, European Union, India for the following indications:

Approved in United States as Xifaxan for:

• Traveler's diarrhea
• Irritable bowel syndrome with diarrhea
• Hepatic encephalopathy

Approved in Canada as Zaxine for:

• Traveler's diarrhea
• Irritable bowel syndrome with diarrhea
• Hepatic encephalopathy

Approved in European Union as Xifaxan for:

• Traveler's diarrhea
• Irritable bowel syndrome with diarrhea
• Hepatic encephalopathy

Approved in India as Ciboz and Xifapill for:

• Traveler's diarrhea
• Irritable bowel syndrome with diarrhea
• Hepatic encephalopathy

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Bausch Health Americas, Inc.

Industry Sponsor

Trials

265

Recruited

82,000+

Dr. Jonathan Sadeh

Bausch Health Americas, Inc.

Chief Medical Officer

MD from Mount Sinai School of Medicine, MSc in Clinical Research from Harvard Medical School

Thomas J. Appio

Bausch Health Americas, Inc.

Chief Executive Officer since 2021

Bachelor's degree in Biology from Rutgers University

Published Research Related to This Trial

In a study of eight patients with chronic active refractory pouchitis, the combination of rifaximin and ciprofloxacin led to significant improvements, with seven patients either achieving remission or showing improvement based on the Pouchitis Disease Activity Index (PDAI) score.

The treatment was well-tolerated with no reported side effects, and after a median follow-up of 30 months, the majority of patients maintained satisfactory pouch function, indicating the long-term efficacy of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin-ciprofloxacin combination therapy is effective in chronic active refractory pouchitis. Abdelrazeq, AS., Kelly, SM., Lund, JN., et al.[2018]

In a study of 16 patients with chronic refractory pouchitis, combination therapy using ciprofloxacin and tinidazole resulted in significant improvements in disease activity and quality of life compared to mesalamine therapy, with a clinical remission rate of 87.5%.

The antibiotic combination was generally well tolerated, although two patients experienced mild adverse effects, indicating that it is a safe and effective treatment option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined ciprofloxacin and tinidazole therapy in the treatment of chronic refractory pouchitis. Shen, B., Fazio, VW., Remzi, FH., et al.[2013]

In a study of 51 patients with antibiotic-dependent pouchitis, 65% maintained remission after 3 months of maintenance therapy with rifaximin, indicating its potential efficacy for long-term management.

Rifaximin was well-tolerated, with only one patient reporting a transient adverse event, suggesting a favorable safety profile for this treatment in maintaining remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin for maintenance therapy in antibiotic-dependent pouchitis. Shen, B., Remzi, FH., Lopez, AR., et al.[2021]

In a study of 43 patients with ulcerative colitis, those treated with ciprofloxacin (CFX) for pouchitis showed significantly higher mutation rates in the gyrA and parC genes associated with antibiotic resistance, indicating a potential decrease in CFX effectiveness.

Specifically, mutation rates at key positions in the gyrA and parC genes were found to be 70%, 84%, and 38% in CFX-treated patients compared to only 13%, 11%, and 5% in untreated patients, highlighting the risk of developing resistance during antibiotic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Quinolone-Resistant Mutations of gyrA and parC Genes after Pouchitis Treatment with Ciprofloxacin. Fukushima, K., Saito, T., Kohyama, A., et al.[2021]

In a study of 205 patients with pouchitis, 81.5% used antibiotics, primarily ciprofloxacin, with long-term use rates of 18% at 5 years and 42% at 20 years post-surgery, indicating a significant need for prolonged antibiotic treatment.

The study found a favorable safety profile for long-term antibiotic use, with only 13.2% reporting mild adverse events and no severe complications like mortalities or serious infections, although the potential for antibiotic resistance remains a concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Antibiotic Treatment in Pouchitis-Patterns of Use and Safety. Bar, N., Avraham, Y., Dubinsky, V., et al.[2022]

About 50% of patients who have undergone IPAA surgery for Ulcerative Colitis experience pouchitis, which can vary widely in symptoms and severity, highlighting the need for better diagnostic criteria.

Ciprofloxacin is more effective than metronidazole for inducing remission in acute pouchitis, while maintenance therapy with ciprofloxacin or the probiotic VSL#3 is recommended for patients with frequent relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and Medical Treatment of Pouchitis In Ulcerative Colitis. Benlice, C., Shen, B., Steele, SR.[2020]

In a pilot study involving 18 patients with active pouchitis, rifaximin showed a trend towards clinical remission, with 25% of patients achieving remission compared to none in the placebo group, although this difference was not statistically significant.

Rifaximin was well tolerated by all participants, indicating a favorable safety profile, but further research with a larger sample size is needed to confirm its efficacy in treating active pouchitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rifaximin for the treatment of active pouchitis: a randomized, double-blind, placebo-controlled pilot study. Isaacs, KL., Sandler, RS., Abreu, M., et al.[2018]

Citations

1. researchgate.net researchgate.net/publication/6269027_Rifaximin_for_the_treatment_of_active_pouchitis_A_randomized_double-blind_placebo-controlled_pilot_study

A randomized, double-blind, placebo-controlled pilot study Twenty-five percent (2/8) of participants in the rifaximin group achieved clinical remission compared to 0% (0/10) of the placebo group (RR: ...

2. nice.org.uk nice.org.uk/advice/esuom30/chapter/Evidence-review-efficacy

Evidence review: efficacy | Pouchitis: rifaximin | Advice The primary outcome was clinical remission at 4 weeks (PDAI score of less than 7 points and a decrease from baseline PDAI score of 3 points).

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17567869/

Rifaximin for the treatment of active pouchitis Two of 8 patients (25%) treated with rifaximin were in clinical remission at week 4 compared to 0 of 9 patients (0%) treated with placebo (P = 0.2059). None of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2442097/

Rifaximin for maintenance therapy in antibiotic-dependent ... The majority (65%) of patients maintained remission for at least 3 months with rifaximin, indicated by a lack of increase in mPDAI symptom ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06312683?term=AREA%5BInterventionSearch%5D(XIFAXAN)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=2

Rifaximin for the Secondary Prevention of Recurrent ... In this study, all patients will be given daily rifaximin for one year after being treated for an initial episode of pouchitis. This study will examine whether ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK562329/

Rifaximin - StatPearls - NCBI Bookshelf Rifaximin is an antibiotic used to treat irritable bowel syndrome with diarrhea, reduce the risk of overt hepatic encephalopathy recurrence in adults, and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4737517/

Rifaximin: A Unique Gastrointestinal-Selective Antibiotic for ... Among 51 patients with antibiotic-dependent pouchitis, 33 (65%) were successfully maintained on rifaximin suppressive therapy for at least 3 months in an open- ...

8. researchgate.net researchgate.net/publication/316896589_A_meta-analysis_of_the_use_of_rifaximin_to_prevent_travellers'_diarrhoea

A meta-analysis of the use of rifaximin to prevent travellers ... Overall, rifaximin offered significant protection rates of 48-72%, with lower protection rates for Asian than Latin American countries. In terms of tolerability ...

9. nice.org.uk nice.org.uk/advice/esuom30/chapter/Evidence-review-safety

Evidence review: safety | Pouchitis: rifaximin | Advice In the study by Shen et al. (2008), rifaximin was well tolerated when used for maintenance for up to 24 months. One person discontinued ...