Ulcerative ColitisPhase 3COMBOMESANCT02665845
Combination Corticosteroids+5-aminosalicylic Acids Compared to Corticosteroids Alone (for Ulcerative Colitis).
A Phase 3 study testing 5-ASA and Corticosteroids in people with Ulcerative Colitis, run by Centre Hospitalier Universitaire de Saint Etienne at 6 sites in 6 countries.
Trial summary
The role of steroids in the treatment of severe ulcerative colitis (UC) exacerbation is well established and recommended by professional societies. Similarly, 5-aminosalycilates (5-ASA) agents in the form of mesalamine/mesalzine are well established proven therapy in mild-moderate UC, and the combination of oral 5-ASA… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- 5-ASA and Corticosteroids
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 6 sitesin 6 countries
- Study dates
- 13 Jun 2016to 11 May 2021
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- UC known and diagnosed by established clinical-endoscopic and histological criteria or newly-diagnosed UC, based on clinical and endoscopic findings, and about to start treatment with corticosteroids.
- Current hospitalization with Severe UC exacerbation as defined by a Lichtiger score of >10
- Age >18
- Has not been on oral systemic corticosteroids more than 14 days prior to hospitalization
- If taking a thiopurine, the dose need to be stable for the last 2 months before admission
Who cannot join
- Pregnant women
- Allergy / unable to take prednisone / hydrocortisone/ 5-ASA.
- Active infection - either enteric or elsewhere
- Severe renal, liver or cardio respiratory comorbidity
- Toxic megacolon, or clinical features suggestive of a need for imminent colectomy
- Treatment with an anti-TNF within the prior 3 months
Show all 10Show fewer
- Prior treatment with cyclosporine or tacrolimus within the prior 3 months
- Alcohol dependency
- Unable or unwilling to provide informed consent
- Participating in other clinical trial within the 2 months prior to admission
Trial locations and contacts
6 sites in 6 countries.
6 sites in 6 countries
Greece1 site
Department of Gastroenterology Venizeleio General Hospital, Leoforos Knosou
Heraklion
Serbia1 site
Zvezdara University Clinical Center, Gastroenterology Department
Belgrade
South Korea1 site
Institute of Gastroenterology and Department of Internal Medicine, Yonsei University College of Medicine
Seoul
About this study
Official title: Combination Corticosteroids+5-aminosalicylic Acids Compared to Corticosteroids Alone in the Treatment of Moderate-severe Active Ulcerative Colitis: A Protocol of a Multi-center Prospective Randomized Investigator Blinded Trial.
The role of steroids in the treatment of severe ulcerative colitis (UC) exacerbation is well established and recommended by professional societies. Similarly, 5-aminosalycilates (5-ASA) agents in the form of mesalamine/mesalzine are well established proven therapy in mild-moderate UC, and the combination of oral 5-ASA with topical (per-rectal enema) 5-ASA was shown to be superior to oral 5ASA alone in patients with mild moderate UC. Thus, in most cases, when a patient with UC experiences a flare while taking 5-ASA therapy, treatment is usually optimized by maximizing the oral dose to 4gr/day and adding topical therapy until the flare is controlled. If this is unhelpful, or if the flare is severe to begin with, corticosteroids are usually prescribed. However, there are very scarce data comparing steroids versus 5-ASA in the treatment of severe UC exacerbation.
The aim of this study is to compare the efficacy of steroids alone vs. combination of steroids + 5-ASA in the treatment of moderate-severe UC exacerbation.
Read the detailed description
The role of steroids in the treatment of severe ulcerative colitis (UC) exacerbation is well established and recommended by professional societies. This recommendation is based on pivotal studies carried 50-60 years ago, by Truelove \&Witts. Similarly, 5-aminosalycilates (5-ASA) agents in the form of mesalamine/mesalzine are well established proven therapy in mild-moderate UC, and the combination of oral 5-ASA with topical (per-rectal enema) 5-ASA was shown to be superior to oral 5ASA alone in patients with mild moderate UC. Thus, in most cases, when a patient with UC experiences a flare while taking 5-ASA therapy, treatment is usually optimized by maximizing the oral dose to 4gr/day and adding topical therapy until the flare is controlled. If this is unhelpful, or if the flare is severe to begin with, corticosteroids are usually prescribed. However, there are very scarce data comparing steroids versus 5-ASA in the treatment of severe UC exacerbation. In 1962 truelove et al compared topical and systemic corticosteroid therapy with sulphasalazine, and found steroids to be superior to sulfasalazine. Importantly, there are no data investigating whether the addition and/or continuation of 5-ASA agents as combination therapy with systemic corticosteroids is superior to corticosteroids alone in patients with moderate-severe active UC. This knowledge gap is pronounced in patients admitted to the hospital for intravenous corticosteroid treatment with moderate severe UC flare, in whom it is currently unknown if the addition of 5-ASA (Oral and/or topical) to corticosteroids will confer additional benefit and improve patients outcomes. Thus, in practical terms, the decision whether to stop or continue 5-ASA treatment or whether to add 5-ASA to steroids in the treatment of moderate-severe UC exacerbation is taken on an arbitrary basis. This is important shortcoming and knowledge gap in current medicine, as patients admitted with moderate-severe UC flare who do not respond to corticosteroids and require salvage therapy with infliximab, cyclosporine, or even urgent colectomy. This makes it prudent to explore any avenue for possible improvement of response to corticosteroids in this setting, for instance by addition of 5ASA.
The aim of this study is: To compare the efficacy of steroids alone vs. combination of steroids + 5-ASA in the treatment of moderate- severe UC exacerbation.
- Conditions
- Ulcerative Colitis
- Being tested
- 5-ASA, Corticosteroids
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-ASADrug
Also called 5-aminosalicylates
5ASA treatment (oral 5ASA will be given to all patients in this arm, in addition to topical 5ASA in patients who tolerate it).
CorticosteroidsDrug
Also called Usual care
Corticosteroids will be given to all patients.
| Study group | Role | What they receive |
|---|---|---|
| 5-ASA group | Experimental | Patients will receive corticosteroids with optimized 5-ASA. Receives: Drug: 5-ASA; Drug: Corticosteroids |
| Control group | Active comparator | Patients will receive corticosteroids alone. Receives: Drug: Corticosteroids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients who respond to the treatment by day 7.
The primary endpoint will be the percentage of patients who respond to the treatment by day 7. Response will be defined by a drop of >3 points in the lichtiger score and an absolute score <10 on the two prior consecutive days without the need for rescue medications or surgery. In patients who improve and are discharged prior to day 7, the lichtiger score will be calculated based on the two last days of hospitalization, provided that at least 3 days of study medications were dispensed. Patients discharged before 3 days of study medications have been administered will be considered in-eligible and will be dropped out of the analyses.
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2016 (estimated)
- Study start13 Jun 2016
- Primary completion11 May 2021
- Study completion11 May 2021
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.
- More trials run by Centre Hospitalier Universitaire de Saint EtienneThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- ROBLIN Xavier, MD, Principal investigator, Centre Hospitalier Universitaire de Saint Etienne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02665845
- Sponsor's protocol ID
- 1508090
- Other IDs
- 2015-002671-21, 2015
- Acronym
- COMBOMESA
- Status last verified
- Aug 2021
- First submitted
- 25 Jan 2016
- Last updated
- 26 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Corticosteroids+5-aminosalicylic Acids Compared to Corticosteroids Alone in the Treatment of Moderate-severe Active Ulcerative Colitis: A Protocol of a Multi-center Prospective Randomized Investigator Blinded Trial.
- ClinicalTrials.gov ID
- NCT02665845
- Acronym / sponsor ID
- COMBOMESA / 1508090
- Conditions
- Ulcerative Colitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de Saint EtienneUniversity, hospital or other
- Study start
- 13 Jun 2016 (actual)
- Primary completion
- 11 May 2021 (actual)
- Study completion
- 11 May 2021 (actual)
- First posted
- 28 Jan 2016 (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 role of steroids in the treatment of severe ulcerative colitis (UC) exacerbation is well established and recommended by professional societies. Similarly, 5-aminosalycilates (5-ASA) agents in the form of mesalamine/mesalzine are well established proven therapy in mild-moderate UC, and the combination of oral 5-ASA with topical (per-rectal enema) 5-ASA was shown to be superior to oral 5ASA alone in patients with mild moderate UC. Thus, in most cases, when a patient with UC experiences a flare while taking 5-ASA therapy, treatment is usually optimized by maximizing the oral dose to 4gr/day and adding topical therapy until the flare is controlled. If this is unhelpful, or if the flare is severe to begin with, corticosteroids are usually prescribed. However, there are very scarce data comparing steroids versus 5-ASA in the treatment of severe UC exacerbation.
The aim of this study is to compare the efficacy of steroids alone vs. combination of steroids + 5-ASA in the treatment of moderate-severe UC exacerbation.
Detailed description
The role of steroids in the treatment of severe ulcerative colitis (UC) exacerbation is well established and recommended by professional societies. This recommendation is based on pivotal studies carried 50-60 years ago, by Truelove \&Witts. Similarly, 5-aminosalycilates (5-ASA) agents in the form of mesalamine/mesalzine are well established proven therapy in mild-moderate UC, and the combination of oral 5-ASA with topical (per-rectal enema) 5-ASA was shown to be superior to oral 5ASA alone in patients with mild moderate UC. Thus, in most cases, when a patient with UC experiences a flare while taking 5-ASA therapy, treatment is usually optimized by maximizing the oral dose to 4gr/day and adding topical therapy until the flare is controlled. If this is unhelpful, or if the flare is severe to begin with, corticosteroids are usually prescribed. However, there are very scarce data comparing steroids versus 5-ASA in the treatment of severe UC exacerbation. In 1962 truelove et al compared topical and systemic corticosteroid therapy with sulphasalazine, and found steroids to be superior to sulfasalazine. Importantly, there are no data investigating whether the addition and/or continuation of 5-ASA agents as combination therapy with systemic corticosteroids is superior to corticosteroids alone in patients with moderate-severe active UC. This knowledge gap is pronounced in patients admitted to the hospital for intravenous corticosteroid treatment with moderate severe UC flare, in whom it is currently unknown if the addition of 5-ASA (Oral and/or topical) to corticosteroids will confer additional benefit and improve patients outcomes. Thus, in practical terms, the decision whether to stop or continue 5-ASA treatment or whether to add 5-ASA to steroids in the treatment of moderate-severe UC exacerbation is taken on an arbitrary basis. This is important shortcoming and knowledge gap in current medicine, as patients admitted with moderate-severe UC flare who do not respond to corticosteroids and require salvage therapy with infliximab, cyclosporine, or even urgent colectomy. This makes it prudent to explore any avenue for possible improvement of response to corticosteroids in this setting, for instance by addition of 5ASA.
The aim of this study is: To compare the efficacy of steroids alone vs. combination of steroids + 5-ASA in the treatment of moderate- severe UC exacerbation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 5-ASA group | Experimental | Drug: 5-ASA, Drug: CorticosteroidsPatients will receive corticosteroids with optimized 5-ASA. |
| Control group | Active comparator | Drug: CorticosteroidsPatients will receive corticosteroids alone. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- UC known and diagnosed by established clinical-endoscopic and histological criteria or newly-diagnosed UC, based on clinical and endoscopic findings, and about to start treatment with corticosteroids.
- Current hospitalization with Severe UC exacerbation as defined by a Lichtiger score of >10
- Age >18
- Has not been on oral systemic corticosteroids more than 14 days prior to hospitalization
- If taking a thiopurine, the dose need to be stable for the last 2 months before admission
Key exclusion criteria (10 listed)
- Pregnant women
- Allergy / unable to take prednisone / hydrocortisone/ 5-ASA.
- Active infection - either enteric or elsewhere
- Severe renal, liver or cardio respiratory comorbidity
- Toxic megacolon, or clinical features suggestive of a need for imminent colectomy
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 |
|---|---|---|
| 5-ASAAlso: 5-aminosalicylates5ASA treatment (oral 5ASA will be given to all patients in this arm, in addition to topical 5ASA in patients who tolerate it). | Drug | 5-ASA group |
| CorticosteroidsAlso: Usual careCorticosteroids will be given to all patients. | Drug | 5-ASA group, Control group |
Primary outcome
Percentage of patients who respond to the treatment by day 7.
Time frame: Day 7
The primary endpoint will be the percentage of patients who respond to the treatment by day 7. Response will be defined by a drop of >3 points in the lichtiger score and an absolute score <10 on the two prior consecutive days without the need for rescue medications or surgery. In patients who improve and are discharged prior to day 7, the lichtiger score will be calculated based on the two last days of hospitalization, provided that at least 3 days of study medications were dispensed. Patients discharged before 3 days of study medications have been administered will be considered in-eligible and will be dropped out of the analyses.
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 26 Aug 2021.
- Individual participant dataSharing planned: No
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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.
ROBLIN Xavier, MD principal investigator
Centre Hospitalier Universitaire de Saint Etienne
6 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 5-ASA and Corticosteroids in people with Ulcerative Colitis, run by Centre Hospitalier Universitaire de Saint Etienne at 6 sites in 6 countries.
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 5 inclusion and 10 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 26 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France, Greece, Israel, Italy, Serbia and 1 more country. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Percentage of patients who respond to the treatment by day 7. (time frame: Day 7). 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 26 Aug 2021.