Ulcerative ColitisPhase 4HERICANCT01408810
Evaluation of Histologic and Endoscopic Remission Induced by Infliximab in Moderate to Severe Ulcerative Colitis
A Phase 4 study testing Infliximab in people with Ulcerative Colitis, run by Grupo de Estudo da Doença Inflamatória Intestinal at 1 site in Portugal.
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. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- Infliximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 sitePortugal
- Study dates
- Feb 2011to Nov 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Subjects must meet all the following inclusion criteria to be considered eligible:
- Must be eligible to start infliximab treatment according to the Portuguese approved Summary of Product Characteristics (SPC-See supplement 15.3)*
- 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.
- Patients with moderate to severe UC - Mayo Score (6-12); endoscopic subscore ≥2
- 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.
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- Patients must be naïve to infliximab or other anti-TNF agents
- 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.
- Patients must be capable of providing written informed consent prior to trial entry.
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Histological and Endoscopic Evaluation of Remission Induced by Infliximab in Moderately to Severely Active Ulcerative Colitis Patients
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.
Read the detailed 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
- Conditions
- Ulcerative Colitis
- Being tested
- Infliximab
- Keywords
- infliximab, ulcerative colitis, histologic remission
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
Also called Remicade
5 mg/Kg, I.V. at weeks 0, 2, 6 and every 8 weeks thereafter
| Study group | Role | What they receive |
|---|---|---|
| Infliximab | Experimental | Infliximab 5 mg/Kg, I.V. at weeks 0, 2, 6 and every 8 weeks thereafter. The treatment should follow infliximab's Summary of Product Characteristics. Receives: Drug: Infliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: histological remission were assessed at week 8
Clinical response
To assess the clinical response in the above patients assessed by Mayo Score at week 8
Measured: clinical response were assessed at week 8
Secondary outcomes (2)
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
Measured: baseline, week 8, week 30 and week 52.
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
Measured: up to week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2011 (estimated)
- Study startFeb 2011
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo de Estudo da Doença Inflamatória Intestinal
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Susana Lopes, MD, Principal investigator, Hospital de São JoãoFrancisco Portela, MD, Principal investigator, Hospitais da Universidade de CoimbraPaula Lago, MD, Principal investigator, General Hospital of Santo AntónioJosé Cotter, MD, Principal investigator, Hospital Nossa Senhora da Oliveira - GuimarãesPaula Peixe, MD, Principal investigator, Centro Hospitalar Lisboa Ocidental
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01408810
- Sponsor's protocol ID
- P06120
- Acronym
- HERICA
- Status last verified
- Dec 2012
- First submitted
- 20 Jul 2011
- Last updated
- 18 Dec 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Histological and Endoscopic Evaluation of Remission Induced by Infliximab in Moderately to Severely Active Ulcerative Colitis Patients
- ClinicalTrials.gov ID
- NCT01408810
- Acronym / sponsor ID
- HERICA / P06120
- Conditions
- Ulcerative Colitis
- Keywords
- infliximab, ulcerative colitis, histologic remission
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Grupo de Estudo da Doença Inflamatória IntestinalUniversity, hospital or other
- Study start
- Feb 2011
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 3 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Infliximab | Experimental | Drug: InfliximabInfliximab 5 mg/Kg, I.V. at weeks 0, 2, 6 and every 8 weeks thereafter. The treatment should follow infliximab's Summary of Product Characteristics. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Subjects must meet all the following inclusion criteria to be considered eligible:
- 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.
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InfliximabAlso: Remicade5 mg/Kg, I.V. at weeks 0, 2, 6 and every 8 weeks thereafter | Drug | Infliximab |
Primary outcome
histological remission
Time frame: histological remission were assessed at week 8
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
Clinical response
Time frame: clinical response were assessed at week 8
To assess the clinical response in the above patients assessed by Mayo Score at week 8
2 secondary outcomes
Histologic Efficacy assessment
Time frame: baseline, week 8, week 30 and week 52.
Correlate histological remission with mucosal healing,faecal calprotectin and lactoferrin levels,number of colectomies,number of hospitalizations,Number of clinical relapses
Time frame: up to week 52
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susana Lopes, MD principal investigator
Hospital de São João
Francisco Portela, MD principal investigator
Hospitais da Universidade de Coimbra
Paula Lago, MD principal investigator
General Hospital of Santo António
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Infliximab in people with Ulcerative Colitis, run by Grupo de Estudo da Doença Inflamatória Intestinal at 1 site in Portugal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
histological remission (time frame: histological remission were assessed at week 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2012.