Evaluation of Histologic and Endoscopic Remission Induced by Infliximab in Moderate to Severe Ulcerative Colitis

Ulcerative Colitis Clinical Trial

— HERICA  

Official title:

Histological and Endoscopic Evaluation of Remission Induced by Infliximab in Moderately to Severely Active Ulcerative Colitis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01408810
• Other study ID #: P06120
• Status: Completed
• Phase: Phase 4
• First received: July 20, 2011
• Last updated: December 17, 2012
• Start date: February 2011
• Est. completion date: November 2012

Study information

• Verified date: December 2012
• Source: Grupo de Estudo da Doença Inflamatória Intestinal
• Contact: n/a
• Is FDA regulated: No
• Health authority: Portugal: Ethics Committee for Clinical ResearchPortugal: Health Ethic CommitteePortugal: National Pharmacy and Medicines Institute
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to assess the relationship between microscopic Geboes index of inflammation and clinical course of ulcerative colitis in patients treated with infliximab. The investigators propose to test the hypothesis if infliximab is able to induce histological remission and then change the clinical course of ulcerative colitis.

Description:

Correlations between histologic disease activity and other assessments of clinical disease activity are not well established despite a good correlation being found between endoscopy and histology, especially during active ulcerative colitis (1,2). Endoscopic healing induced by infliximab in Crohn's disease patients was associated with a significant reduction in surgeries and hospitalizations (3). Histological recovery in ulcerative colitis is often incomplete and some studies have shown that microscopic evidence of inflammation is common even in patients with clinically and quiescent colitis assessed by sigmoidoscopy (4,5). Although this fact has not yet been completely elucidated, it is suggested that some patients with residual microscopic acute inflammation may be more prone to relapse (2). The prognostic importance of microscopic inflammation is unknown. Given that the rectum is always involved in ulcerative colitis and inflammatory activity is diffuse and restricted to the mucosa, the collection of samples from the rectal and sigmoid mucosa are potentially useful tools for evaluating disease severity. In addition, there is a strong correlation between the levels of calprotectin and the degree of inflammation as assessed by endoscopic and histologic criteria (6). Therefore, the measurement of faecal calprotectin and lactoferrin may also provide as valuable non-invasive tools to assess disease activity and optimize the treatment in UC patients.

Histologically, active disease is defined by the presence of neutrophils in conjunction with epithelial cell damage. Analysis generally relies on the examination of H & E-stained sections. Two samples are suggested as more appropriated because it is well-known that treatment may induce variations in the expression of inflammation intensity. Several histological scores were proposed, however, Geboes index (7) has been validated and tested for reproducibility and has 5 domains: structural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulceration. The Geboes index has a more elaborated grading of crypt lesions and surface epithelial damage than other proposed indexes. The aim of this study is to assess the relationship between microscopic Geboes index of inflammation and clinical course of ulcerative colitis in patients treated with infliximab. The investigators propose to test the hypothesis if infliximab is able to induce histological remission and then change the clinical course of ulcerative colitis

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Subjects must meet all the following inclusion criteria to be considered eligible:

1. Must be eligible to start infliximab treatment according to the Portuguese approved Summary of Product Characteristics (SPC-See supplement 15.3)*

2. Patients must be older than 18 years of age up to 65 years of age at the time of informed consent, of both gender and any race.

3. Patients with moderate to severe UC - Mayo Score (6-12); endoscopic subscore =2

4. Regarding the previous treatment exposure:

4.1 Patients must have responded inadequately to corticosteroids at least a dose of 40mg/day with or without 5-ASA or patients steroid-dependent* 4.2- Patients must have responded inadequately to azathioprine or 6-MP (treatment with thiopurines must be at least 3 months in duration) or be intolerant to these agents.

5. Patients must be naïve to infliximab or other anti-TNF agents

6. No history of latent or active TB prior to screening. No signs or symptoms suggestive of active TB upon medical history and/or physical examination.

7. Patients must be capable of providing written informed consent prior to trial entry.

8. Subjects must be willing and able to adhere to visit protocol schedule and procedures.

• Patients must have responded inadequately to corticosteroids at least a dose of 40mg/day with or without 5-ASA or patients steroid-dependent with a Mayo Score (6-12), endoscopic subscore >2. Steroid-dependent is defined as: patients unable to reduce steroids below 10mg/day within 3 months of starting steroids and patients who have a relapse within 3 months of stopping steroids.

Exclusion Criteria:

• 1- Any "Contraindication" as specified in the Portuguese infliximab approved Summary of Product Characteristics (See Supplement 15.3) 2- Patients with severe anemia (haemoglobin<8.0 g/dL) 3- Any malignancy in the past 5 years, including lymphoproliferative disorders 4- Existence of not removed adenomatous polyps 5- History of opportunistic infections in the last 6 months 6- Subjects who have a known viral infection such as CMV, HIV, HBV or HCV 7- Patients with a history of demyelinating diseases 8- Pregnant or breastfeeding women 9- Topical treatment with 5-ASA and steroids 10-Patients with only rectal involvement

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Infliximab
5 mg/Kg, I.V. at weeks 0, 2, 6 and every 8 weeks thereafter

Locations

Country	Name	City	State
Portugal	Hospital de São João	Porto

Sponsors (1)

Lead Sponsor	Collaborator
Grupo de Estudo da Doença Inflamatória Intestinal

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	histological remission	To assess if infliximab is able to induce histological remission in patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy, including corticosteroids and 6-MP/AZA or who are intolerant or have medical contraindications for such therapies using Geboes criteria at week 8	histological remission were assessed at week 8	No
Primary	Clinical response	To assess the clinical response in the above patients assessed by Mayo Score at week 8	clinical response were assessed at week 8	No
Secondary	Histologic Efficacy assessment	To assess the impact of infliximab histologically, four biopsies will be collected from distinct areas (two from rectum and two from sigmoid) from each patient	baseline, week 8, week 30 and week 52.	No
Secondary	Correlate histological remission with mucosal healing,faecal calprotectin and lactoferrin levels,number of colectomies,number of hospitalizations,Number of clinical relapses	Correlate histological remission with: Mucosal healing Faecal calprotectin and lactoferrin levels Number of colectomies up to week 52 Number of hospitalizations up to week 52 Number of clinical relapses up to week 52	up to week 52	No