- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02425852
A Randomized, Multicenter Open Label Study Comparing Early Administration of Azathioprine Plus IFX to Steroids Plus Azathioprine for Acute Severe Colitis (ACTIVE)
A Randomized, Multicenter Open Label Study Comparing Early Administration of Azathioprine Plus Infliximab to Corticosteroids Plus Azathioprine for Acute Severe Colitis
PHASE : IV TYPE OF STUDY : With direct benefit. DESCRIPTIVE : Multicentre, randomized, open label study. INCLUSION CRITERIA : Acute severe ulcerative colitis. OBJECTIVES : To compare the efficacy and safety of early administration of the combination therapy with infliximab and azathioprine with steroids and azathioprine in patients with acute severe ulcerative colitis treated with intravenous steroids.
STUDY TREATMENTS : All patients :
Intravenous steroids (0.8 mg/kg/day of methylprednisolone or equivalent) for 5 days.
Combination therapy arm:
Infliximab 5 mg/kg plus Azathioprine 2-2.5 mg/kg/day.
Azathioprine arm:
Steroids tapering for 3 months and Azathioprine 2-2.5 mg/kg/day.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
NUMBER OF PATIENTS : 73 patients in each group i.e. a total of 146patients. RECRUITMENT PERIOD : 36 months STUDY DURATION : 12 months
PRIMARY END POINT : Treatment failure is defined by:
- Absence of steroid-free remission at W52 according to the total Mayo Disease Activity Index score
- OR Absence of mucosal healing (Mayo endoscopic subscore 0-1)
- OR Adverse event leading to treatment interruption
- OR Colectomy
- OR Death
- OR Infliximab withdrawal in the combination therapy group OR Infliximab introduction in the azathioprine group SECONDARY END POINT: - Clinical response and remission at D7, W14 and W52 (according to Lichtiger score and total Mayo Disease Activity Index score)
- Endoscopic and histological response
- Mucosal healing (partial endoscopic Mayo subscore 0)
- Colectomy rate
- Adverse events rate
- Fecal calprotectin
- Health-economic outcome
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Justine POLLET
- Email: jpollet@getaid.org
Study Locations
-
-
-
Besancon, France, 25030
- CHU Besançon
-
Clermont-Ferrand, France, 67000
- CHU de CLERMONT FERRAND- Hopital Estain
-
Clichy, France, 92110
- APHP- Hopital Beaujon
-
Colombes, France, 92700
- Hopital Louis Mourrier
-
Creteil, France, 94010
- Henri Mondor Hospital
-
Le Kremlin-Bicêtre, France
- CHU Kremlin Bicêtre
-
Lille, France
- CHRU Lille
-
Montpellier, France, 34295
- CHU Montpellier
-
Nice, France, 06200
- CHU de NICE- Hopital Archet 2
-
Paris, France, 75014
- Hopital Saint Joseph
-
Paris, France, 75010
- Hopital Saint Louis
-
Paris, France, 75012
- Hopital St Antoine
-
Rennes, France
- CHU Rennes - Hôpital Pontchaillou
-
Rouen, France, 76031
- CHU Rouen
-
St Etienne, France, 42270
- CHU Saint Etienne
-
Vandoeuvre Les Nancy, France, 54500
- CHU Nancy - Hôpital Brabois
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age > 18 years.
- Diagnosis of UC according to Lennard-Jones criteria (Appendix 1).
- Endoscopically demonstrated colorectal lesions localized above the anal margin and extending at least up to 15cm proximally (Endoscopic Mayo subscore ≥ 2).
- Acute flare requiring hospitalization
- Severe acute flare of UC with a Lichtiger Index score > 10 at Day -3
- Adequate contraception for male or female subjects of childbearing potential, which will be continued throughout the study and at least 3 months after study termination.
3.2 EXCLUSION CRITERIA
- Pregnant or breast-feeding woman.
- Previous treatment with infliximab.
- Treatment with adalimumab or golimumab within 8 weeks before randomization
- Treatment with vedolizumab within 4 weeks before randomization
- Azathioprine or 6-mercaptopurine treatment initiated more than 4 weeks before screening.
- Ongoing intravenous steroids for more than 96 hours at time of the screening
- Contraindication for anti-TNF therapy
- Indication for immediate surgery.
- History of colorectal dysplasia.
- Diagnosis of Crohn's disease or indeterminate colitis
- Positive stool tests for amoebiasis and/or positive bacteriological culture for Salmonella, Shigella, Yersinia and Campylobacter and/or presence of Clostridium difficile B toxin in the stools.
- Renal failure (creatininemia > upper limit of normal laboratory value).
- Uncontrolled high blood pressure.
- HIV, HBV viral infection (except the presence of positive anti-HBs antibodies) with serology not older than 3 months.
- Uncontrolled bacterial or active viral infection.
- Past medical history of malignant condition in the last 5 years (including leukaemia, lymphoma and myelodysplasia) except for baso-cellular cutaneous cancers.
- Past medical history of myocardial infarction or heart failure.
- Intradermal reaction to Tuberculin (Tubertest® 5 units) > 5mm or positive interferon-gamma release assay (Quantiferon®)
- Active tuberculosis
- Untreated latent tuberculosis (see national recommendations. Appendix 2).
- Abnormal blood count with polynuclear neutrophils < 1,500 G/L or white cells < 3,000, or platelets < 100,000 G/L.
- Unexplained rise higher than 3 times the normal level for transaminases, alkaline phosphatases and/or higher than twice the normal level for bilirubin.
- Severe acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in judgement of the investigator, would make the subject inappropriate for entry in this study.
- Subjects who, in the opinion of the investigator, will be uncooperative or unable to comply with study procedures.
- Participation in another clinical trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Combination therapy arm
Infliximab 5 mg/kg plus Azathioprine 2-2.5 mg/kg/day.
Azathioprine will be introduced at day 5-7 and continued until week 52.
Azathioprine dose regimen will be between 2 and 2.5 mg/kg/d, as close as possible to 2.5 mg/kg/d, or to 1.5 mg/kg/d for 6-mercaptopurine, in one daily intake.
|
Azathioprine alone versus Azathioprine and IFX
|
Active Comparator: Azathioprine arm
Intravenous steroids will be continue until day 2. Then, steroid therapy will be orally administered at a dose of 40-60 mg/day ou 1 mg/kg/day prednisolone (or equivalent) and progressively reduced by 10mg step every week to 20mg per day, and then reduced by 5mg step every week until stopped. Hydrocortisone intake to prevent steroid weaning will be authorized until supradrenal function normalization. In patients with clinical response at day 7, Azathioprine will be introduced at day 5-7 and continued until week 52. Azathioprine dose regimen will be between 2 and 2.5 mg/kg/d, as close as possible of 2.5 mg/kg/d, or of 1.5 mg/kg/d for 6-mercaptopurine, in one daily intake. |
Azathioprine alone versus Azathioprine and IFX
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of patients with treatment failure at week 52.
Time Frame: Week 52
|
Failure is defined as:
|
Week 52
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of patients in clinical response at day 7
Time Frame: 7 days
|
Percentage of patients in clinical response at day 7 (Lichtiger Index score<10 with a decrease of at least 3 points compared with the baseline score) and at week 14 and week 52 (a decrease from baseline in the Mayo score ≥30% and ≥3 points, accompanied by either a rectal bleeding subscore of 0 or 1 or a decrease from baseline in the rectal bleeding subscore ≥1) - Percentage of patients in clinical remission at day 7, week 14 and week 52 |
7 days
|
Collaborators and Investigators
Investigators
- Principal Investigator: Aurélien Amiot, MD, Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
- Principal Investigator: Laurent Peyrin-Biroulet, MD, PhD, Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Gastrointestinal Diseases
- Gastroenteritis
- Colonic Diseases
- Intestinal Diseases
- Colitis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Dermatologic Agents
- Tumor Necrosis Factor Inhibitors
- Prednisolone
- Infliximab
- Azathioprine
- Hydrocortisone
Other Study ID Numbers
- GETAID 2015-02
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Ulcerative Colitis
-
Ferring PharmaceuticalsCompletedActive Ulcerative Colitis | Remission of Ulcerative ColitisCanada
-
Palatin Technologies, IncRecruitingUlcerative Colitis | Ulcerative Colitis Flare | Ulcerative Colitis Acute | UlcerativeUnited States
-
Theravance BiopharmaCompletedUlcerative Colitis, Active Severe | Ulcerative Colitis, Active ModerateUnited States, Georgia, Moldova, Republic of, Romania
-
Rise Therapeutics LLCUniversity of Colorado, Denver; Mayo ClinicRecruitingUlcerative Colitis | Ulcerative Colitis Chronic Moderate | Ulcerative Colitis Chronic | Ulcerative Colitis Chronic MildUnited States
-
Altheus Therapeutics, Inc.UnknownUlcerative Colitis | Left-sided Ulcerative Colitis | Distal Ulcerative ColitisUnited States
-
Assistance Publique - Hôpitaux de ParisMRSU 938 - Research Center of Saint AntoineNot yet recruitingPediatric Ulcerative Colitis in RemissionFrance
-
Protagonist Therapeutics, Inc.CompletedUlcerative Colitis Chronic Moderate | Ulcerative Colitis Chronic SevereUnited States, Austria, Bulgaria, Canada, Georgia, Germany, Hungary, Italy, Korea, Republic of, Poland, Russian Federation, Serbia, Ukraine
-
Theravance BiopharmaCompletedActive Mild Ulcerative Colitis, Active Moderate Ulcerative Colitis, Healthy SubjectsUnited States
-
Academisch Medisch Centrum - Universiteit van Amsterdam...University Medical Center Groningen; UMC UtrechtRecruitingUlcerative Colitis | Ulcerative Colitis Flare | Ulcerative Colitis AcuteNetherlands
-
Immune PharmaceuticalsUnknownUlcerative Colitis, Active Severe | Ulcerative Colitis, Active ModerateIsrael
Clinical Trials on Infliximab
-
Onze Lieve Vrouwe GasthuisSanteonUnknown
-
Merck Sharp & Dohme LLCIntegrated Therapeutics GroupTerminatedRheumatoid Arthritis
-
Diakonhjemmet HospitalSouth-Eastern Norway Regional Health AuthorityCompletedRheumatoid Arthritis | Crohn's Disease | Ulcerative Colitis | Psoriatic Arthritis | Spondyloarthritis | Psoriasis ChronicNorway
-
PfizerCompleted
-
NYU Langone HealthWithdrawnInflammatory Bowel Disease
-
Centre hospitalier de l'Université de Montréal...Ottawa Hospital Research Institute; Maisonneuve-Rosemont Hospital; Niagara Health... and other collaboratorsRecruiting
-
PfizerCompletedPsoriasis Vulgaris | Pustular Psoriasis | Psoriasis Arthropathica | Erythrodermic PsoriasisJapan
-
Janssen Research & Development, LLCJanssen Biologics BVCompletedUlcerative ColitisUnited States, France, United Kingdom, Belgium, Switzerland, Israel, Canada, Australia, Netherlands, New Zealand, Austria, Germany, Denmark, Czechia, Argentina
-
BiocadCompletedAnkylosing SpondylitisRussian Federation, Belarus
-
European Organisation for Research and Treatment...CompletedMyelodysplastic SyndromesFrance, Belgium, Netherlands, Czech Republic, Italy, Germany