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Ciprofloxacin for the Prevention of Postoperative Endoscopic Recurrence in Crohn's Disease

Primary Purpose

Crohn's Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Ciprofloxacin

Placebo

About this trial

This is an interventional prevention trial for Crohn's Disease focused on measuring Postoperative recurrence, inflammatory bowel disease

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Signed informed consent.
Man or woman between 18 and 70 years of age.
Diagnosis of Crohn's disease confirmed during index surgery.
Detailed assessment of disease localization by colonoscopy, small bowel radiography, and/or other appropriate methods (e.g., MRI, CT) within 6 months prior inclusion into the study.
Resection for ileal or ileo-colonic Crohn's disease with ileo-colonic anastomosis (i.e., without grossly visible disease at the resection margins); neoterminal ileum should be assessable by endoscopy.
Ability to start oral nutrition and medication intake within 14 days after index surgery.
Negative pregnancy test at screening visit in females of childbearing potential.
Use of appropriate contraceptive methods for females of childbearing potential and males with procreative capacity during treatment.

Exclusion Criteria:

Short bowel syndrome.
Previous long term therapy with ciprofloxacin (> 6 weeks prior before surgery)
Patients in whom any visible lesions at the anastomosis were left after index surgery.
Serious secondary illnesses of an acute or chronic nature, which in the opinion of the Investigator renders the patient unsuitable for inclusion into the study.
Dementia
Uncontrolled Diabetes Type I type II
Known drug abuse
Known parasitic disease of the digestive system
Active replicating Hepatitis B or Hepatitis C
HIV-infection
Seizure disorder
Serum creatinine levels exceeding 1.5 mg/dL or 130 μmol/L.
Presence of an ileal or colonic stoma.
Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years).
Application of non-steroidal anti-inflammatory drugs as long term treatment.
Known intolerance/hypersensitivity to ciprofloxacin or other quinolones or drugs of similar chemical structure or pharmacological profile.
Chronic use of CYP1A2 substrates (aminophylline, fluvoxamine, mexiletine, mirtazapine, ropinirole, tizanidine, trifluoperazine)
Well-founded doubt about the patient's cooperation.
Existing pregnancy, lactation, or intended pregnancy or impregnation within the next 3 months.
Non-use of appropriate contraceptives in females of childbearing potential (e.g. condoms, intrauterine device [IUD], hormonal contraception for females, or a means of contraception for a particular patient considered adequate by the responsible investigator) during treatment.
Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial.

Sites / Locations

University of North Carolina

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm Description

Ciprofloxacin 500 mg bid

Placebo bid

Outcomes

Primary Outcome Measures

Safety and Tolerability of Ciprofloxacin

Adverse events (AE) Discontinuation of study drug due to probably study drug related AE

Secondary Outcome Measures

Endoscopic Recurrence Under Postoperative Treatment With Study Medication at 6 Months

Full Information

NCT ID

NCT00609973

First Posted

January 24, 2008

Last Updated

March 21, 2013

Sponsor

University of North Carolina, Chapel Hill

Collaborators

Crohn's and Colitis Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT00609973

Brief Title

Ciprofloxacin for the Prevention of Postoperative Endoscopic Recurrence in Crohn's Disease

Official Title

Double-blind, Placebo Controlled, Randomized, Multicentre, Pilot Study on the Safety and Efficacy of Ciprofloxacin for Prophylactic Prevention of Postoperative Endoscopic Recurrence in Crohn's Disease Patients

Study Type

Interventional

2. Study Status

Record Verification Date

March 2013

Overall Recruitment Status

Completed

Study Start Date

May 2008 (undefined)

Primary Completion Date

October 2011 (Actual)

Study Completion Date

December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of North Carolina, Chapel Hill

Collaborators

Crohn's and Colitis Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Despite extensive medical treatment, surgical resection is required in approximately 70% of the patients at some time. However, recurrence of the disease after operation occurs in the majority of patients and is a serious limitation of surgical management. Therapeutic options to maintain postoperative clinical remission are urgently needed. Several drugs including mesalazine, antibiotics (metronidazole, ornidazole) and azathioprine or 6-mercaptopurine have been studied in the past. But the efficacy is very limited (mesalazine), overshadowed by intolerability during long-term therapy (metronidazole, ornidazole) or inconclusive (azathioprine or 6-mercaptopurine). Research demonstrating the absence of inflammation in patients with diverting ileostomy and the clinical benefit of a postoperative antibiotic therapy using metronidazole or ornidazole implicates a role of the resident bacterial flora in the postoperative relapse. Ciprofloxacin has a broad antibacterial spectrum. More interestingly it also suppresses E. coli strains, which can be found in high numbers in early and chronic ileal lesions of Crohn's disease patients Ciprofloxacin has demonstrated beneficial effects in the therapy of inflammatory bowel diseases, but the available data of the effectiveness of ciprofloxacin allow only a very limited judgement of the safety and tolerability of a 6 months therapy of ciprofloxacin. Therefore an exploratory multicenter prospective, placebo-controlled trial is planned to analyze the safety and tolerability of a 6 months therapy with ciprofloxacin compared to placebo in 40 patients (randomly assigned in a 1:1 ratio) undergoing ileocecal resection (or resection of parts of the colon). If this therapeutic regimen demonstrates tolerability, a second larger study improving the superiority of ciprofloxacin versus placebo can be initiated.

Detailed Description

Despite extensive medical treatment, surgical resection is required in approximately 70% of the patients at some time. However, recurrence of the disease after operation occurs in the majority of patients and is a serious limitation of surgical management. In this setting the bacterial flora plays an important role as demonstrated by the benefit of a postoperative antibiotic therapy with either metronidazole or ornidazole or the absence of inflammation in patients with diverting ileostomy. However, both aforementioned antibiotic regimens have numerous adverse events limiting the value of this therapy in daily clinical practice. Ciprofloxacin suppresses the gram negative aerobic bacterial flora including E.coli strains, which can be found in early and chronic ileal lesions of Crohn's disease patients. A limited number of clinical data suggest efficacy of this drug in patients with established Crohn's disease. This exploratory multicenter prospective, placebo-controlled trial will analyze the safety and tolerability of a 6 months therapy with ciprofloxacin compared to placebo in 40 patients (randomly assigned in a 1:1 ratio) undergoing ileocecal resection (or resection of parts of the colon) with primary anastomosis. No other treatments for Crohn's disease will be permitted. The primary objective of this study is to assess the safety and tolerability of a 6 months therapy of ciprofloxacin (500 mg bid) vs. placebo tablets for prevention of endoscopic recurrence in postoperative Crohn's disease patients. The secondary objectives of this study are to evaluate the endoscopic recurrence in the neoterminal ileum and at the ileocolonic anastomosis as well as the extent of colonic lesions. Additionally bioptic samples at the anastomotic site and patient DNA samples will be collected for later analysis of bacterial ribosomal 19S RNA and DNA polymorphisms (such as NOD2 or IL-23). The clinical data generated by this study will serve as a basis for a definitive clinical trial investigating the effectiveness of ciprofloxacin in the prevention of endoscopic recurrence in postoperative Crohn's disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Crohn's Disease

Keywords

Postoperative recurrence, inflammatory bowel disease

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

Ciprofloxacin 500 mg bid

Arm Title

Arm Type

Placebo Comparator

Arm Description

Placebo bid

Intervention Type

Drug

Intervention Name(s)

Ciprofloxacin

Intervention Description

Ciprofloxacin 500 mg oral bid for 6 months

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo bid for 6 months

Primary Outcome Measure Information:

Title

Safety and Tolerability of Ciprofloxacin

Description

Adverse events (AE) Discontinuation of study drug due to probably study drug related AE

Time Frame

6 Months

Secondary Outcome Measure Information:

Title

Endoscopic Recurrence Under Postoperative Treatment With Study Medication at 6 Months

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Signed informed consent. Man or woman between 18 and 70 years of age. Diagnosis of Crohn's disease confirmed during index surgery. Detailed assessment of disease localization by colonoscopy, small bowel radiography, and/or other appropriate methods (e.g., MRI, CT) within 6 months prior inclusion into the study. Resection for ileal or ileo-colonic Crohn's disease with ileo-colonic anastomosis (i.e., without grossly visible disease at the resection margins); neoterminal ileum should be assessable by endoscopy. Ability to start oral nutrition and medication intake within 14 days after index surgery. Negative pregnancy test at screening visit in females of childbearing potential. Use of appropriate contraceptive methods for females of childbearing potential and males with procreative capacity during treatment. Exclusion Criteria: Short bowel syndrome. Previous long term therapy with ciprofloxacin (> 6 weeks prior before surgery) Patients in whom any visible lesions at the anastomosis were left after index surgery. Serious secondary illnesses of an acute or chronic nature, which in the opinion of the Investigator renders the patient unsuitable for inclusion into the study. Dementia Uncontrolled Diabetes Type I type II Known drug abuse Known parasitic disease of the digestive system Active replicating Hepatitis B or Hepatitis C HIV-infection Seizure disorder Serum creatinine levels exceeding 1.5 mg/dL or 130 μmol/L. Presence of an ileal or colonic stoma. Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years). Application of non-steroidal anti-inflammatory drugs as long term treatment. Known intolerance/hypersensitivity to ciprofloxacin or other quinolones or drugs of similar chemical structure or pharmacological profile. Chronic use of CYP1A2 substrates (aminophylline, fluvoxamine, mexiletine, mirtazapine, ropinirole, tizanidine, trifluoperazine) Well-founded doubt about the patient's cooperation. Existing pregnancy, lactation, or intended pregnancy or impregnation within the next 3 months. Non-use of appropriate contraceptives in females of childbearing potential (e.g. condoms, intrauterine device [IUD], hormonal contraception for females, or a means of contraception for a particular patient considered adequate by the responsible investigator) during treatment. Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hans H Herfarth, MD, PhD

Organizational Affiliation

University of North Carolina

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of North Carolina

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

12. IPD Sharing Statement

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Ciprofloxacin for the Prevention of Postoperative Endoscopic Recurrence in Crohn's Disease

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