- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02177071
A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy (SPARE)
Phase IV
Design : Prospective, open-label, randomized three-arms study
Main Inclusion criteria Luminal Crohn's disease patients with steroid free remission for at least 6 months and a combination therapy with infliximab and anti-metabolites for at least 8 months
Primary objective To demonstrate that Infliximab scheduled maintenance with or without antimetabolites is superior to antimetabolites alone to maintain sustained steroid-free remission over 2 years, while the latter is non inferior with regards to the mean time spent in remission over the same duration
Main co-primary end points Clinical relapse rate at 2 years Mean remission duration within 2 years Study treatment Infliximab, Mercaptopurine, azathioprine, methotrexate.
Number of subjects 225 randomized patients (75 per arm)
Study duration: 3 + 2 years Enrollment: 3 years Follow-up: 2 years
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
3. STUDY OBJECTIVES 3.1. Primary objective To assess the effect of two withdrawal strategies over two years in patients with stable remission for more than 6 months on combination therapy with infliximab and antimetabolites, and demonstrate that continued combination of infliximab and antimetabolites or continued monotherapy with infliximab are both superior to antimetabolites alone for maintaining sustained steroid-free clinical remission, while antimetabolites alone are non-inferior with regards to the mean time spent in remission 3.2. Secondary objectives
- To identify baseline predictive factors of relapse in the three study groups.
- To assess the ability of blood CRP and fecal calprotectin to predict short term relapse in the three groups.
- To assess time spent inclinical remission in the three groups.
- To assess the rate of treatment failure in the three study groups.
- To assess the time to treatment failure in the three study groups.
- To assess progression of bowel damage in the three groups.
- To assess the safety and efficacy of infliximab retreatment in the antimetabolites group.
- To assess safety in the three study groups.
- To assess the health related quality of life in the three study groups.
- To assess direct and indirect costs in the three study groups.
- To assess evolution of blood CRP and fecal calprotectin in the three study groups.
- To assess evolution of infliximab trough levels and ATI in the two infliximab scheduled maintenance groups.
- To assess genetic association with the various clinical and biological outcomes.
- To assess the impact of 6TGN levels on the various clinical and biological outcomes in the purine treated patients 4. STUDY POPULATION 4.1. Selection of study population Patients to be included are those who have been in steroid free remission for at least 6 months and with scheduled infliximab/antimetabolites combination therapy for at least 8 months, with a scheduled infliximab treatment administrated every 8 weeks for the last 4 months.
4.2. Source of recruitment Patients are recruited from participating GETAID IBD-centers in France, Belgium and SOIBD IBD-centers in Sweden, and selected centres in UK, Germany, Netherland and Australia 4.3. Inclusion criteria
To be eligible all of the following criteria must be met:
- Diagnosis of Crohn's disease.
- Male or female, age > 18 years.
- Currently treated with a combination therapy with infliximab and anti-metabolites for luminal Crohn's disease.
- Combined therapy with scheduled infliximab and anti-metabolites for at least 8 months.
- Scheduled administration of infliximab 5 mg/Kg every 8 weeks over the last 4 months.
- Antimetabolites administered at a stable dosage for the last 3 months: at least 1 mg/Kg or 2 mg/Kg for mercaptopurine and azathioprine, respectively, or the highest tolerated dosage if intolerance to standard dose;(lower dose than standard dose is also allowed if 6 TGN > 235 pmol) ; at least 15 mg/week subcutaneously for methotrexate.
- Patients in steroid free clinical remission for at least 6 months according to retrospective assessment of the patients' files.
- CDAI < 150 at baseline.
- A contraceptive during the whole study
- Patients able to understand the information provided to them and to give written informed consent for the study
4.4. Exclusion criteria
- Patients who have presented a severe acute or delayed reaction to infliximab.
- Perianal fistulae as the main indication for infliximab treatment
- Active perianal/abdominal fistulae at time of inclusion, defined by active drainage
- Patients with ostomy or ileoanal pouch
- Pregnancy or planned pregnancy during the study
- Inability to follow study procedures as judged by the investigator
- Non-compliant subjects.
- Participation in another therapeutic study
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Melbourne, Australia
- St Vincent Hospital
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Gent, Belgium, 9000
- Gent University Hospital
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Province De Liège
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Liege, Province De Liège, Belgium, 4000
- CHU LIEGE - Sart Tilman
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Paris, France, 75014
- Hôpital Saint Joseph
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Auvergne Rhone Alpes
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Clermont-ferrand, Auvergne Rhone Alpes, France, 63003
- CHU Clermont-Ferrand
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Pierre Benite, Auvergne Rhone Alpes, France, 69495
- CHU Lyon
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St Etienne, Auvergne Rhone Alpes, France, 42270
- CHU Saint Etienne
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Bourgogne-Franche-Comte
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Besancon, Bourgogne-Franche-Comte, France, 25030
- CHU Besançon
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Bretagne
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Rennes, Bretagne, France, 35033
- CHU Rennes
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Centre Val De Loire
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Tours, Centre Val De Loire, France, 37044
- CHU Tours
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Grand Est
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Reims, Grand Est, France, 51092
- CHU Reims
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Vandoeuvre Les Nancy, Grand Est, France, 54500
- CHU Nancy
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Hauts De France
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Amiens, Hauts De France, France, 80054
- CHU Amiens
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Lille, Hauts De France, France, 59000
- CHU Lille
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Valenciennes, Hauts De France, France, 59300
- Chr Valencienne
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Ile De France
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Clichy, Ile De France, France, 92110
- Hopital Beaujon
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Le Kremlin Bicetre, Ile De France, France, 94275
- Hôpital Bicêtre
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Le Kremlin-Bicêtre, Ile De France, France, 94270
- CHU Kremlin Bicêtre
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Paris, Ile De France, France, 75010
- Hôpital Saint Louis
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Paris, Ile De France, France, 75012
- Hopital St Antoine
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Paris, Ile De France, France, 75674
- Montsouris Mutualist Institute
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Normandie
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Caen, Normandie, France, 14033
- Caen Unversity Hospital
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Nouvelle-aquitaine
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Pessac, Nouvelle-aquitaine, France, 33700
- CHU Bordeaux - Pessac
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Occitanie
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Montpellier, Occitanie, France, 34295
- CHU Montpellier
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Toulouse, Occitanie, France, 31403
- CHU Toulouse
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Pays De La Loire
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Nantes, Pays De La Loire, France, 44093
- CHU Nantes
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Provences Alpes Cote d'Azur
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Nice, Provences Alpes Cote d'Azur, France, 06202
- CHU Nice
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of Crohn's disease.
- Male or female, age > 18 years.
- Currently treated with a combination therapy with infliximab and anti-metabolites for luminal Crohn's disease.
- Combined therapy with scheduled infliximab and anti-metabolites for at least 8 months.
- Scheduled administration of infliximab 5 mg/Kg every 8 weeks over the last 4 months.
- Antimetabolites administered at a stable dosage for the last 3 months: at least 1 mg/Kg or 2 mg/Kg for mercaptopurine and azathioprine, respectively, or the highest tolerated dosage if intolerance to standard dose; at least 15 mg/week subcutaneously for methotrexate.
- Patients in steroid free clinical remission for at least 6 months according to retrospective assessment of the patients' files.
- CDAI < 150 at baseline.
- A contraceptive during the whole study for childbearing potential female patients.
- Patients able to understand the information provided to them and to give written informed consent for the study
Exclusion Criteria:
- Patients who have presented a severe acute or delayed reaction to infliximab.
- Perianal fistulae as the main indication for infliximab treatment
- Active perianal/abdominal fistulae at time of inclusion, defined by active drainage
- Patients with ostomy or ileoanal pouch
- Pregnancy or planned pregnancy during the study
- Inability to follow study procedures as judged by the investigator
- Non-compliant subjects.
- Participation in another therapeutic study
- Steroid use ≤6 months prior to screening
- Currently receiving steroids, immunosuppressive agents (other than purine, methotrexate), biologic treatment (other than infliximab) or thalidomide
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 |
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No Intervention: INFLIXIMAB AND ANTI METABOLITE
continuing scheduled infliximab treatment and anti-metabolite
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Other: STOP INFLIXIMAB CONTINUING ANTI METABOLITE
discontinuing infliximab and continuing the anti-metabolite
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Other: CONTINUING INFLIXIMAB AND discontinuing anti-metabolites
CONTINUING INFLIXIMAB AND DISCONTINUING ANTI METABOLITE
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
co-primary efficacy end points
Time Frame: 2 ans
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There will be two co-primary efficacy end points Relapse rate at 2 years, relapse being defined by either one of the following events:
Mean restricted time spent in remission This time will be computed in all patients, from baseline (CDAI <150 and with absence of fistula drainage) until relapse, as defined above, within the 2 first years. First and subsequent remissions will be summed up within the two first years. |
2 ans
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
relapse in each arm.
Time Frame: 2 years
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2 years
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Sustained clinical remission
Time Frame: 2years
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Sustained clinical remission defined by CDAI<150 without steroids over two years.
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2years
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Treatment failure
Time Frame: 2 years
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2 years
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Tissue damage progression
Time Frame: 2 years
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- Tissue damage progression will be assessed by the Lémann Score absolute and relative change between baseline and en of the study (2 years).
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2 years
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Endoscopic remission
Time Frame: 2 years
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Endoscopic remission at the end of study
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2 years
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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disability index
Time Frame: 2 YEARS
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disability index
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2 YEARS
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adverse events and SAE
Time Frame: 2 YEARS
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adverse events and SAE, events related to re-infusions,
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2 YEARS
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BIOLOGICS
Time Frame: 2 YEARS
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trough levels of infliximab, ATI , hsCRP, fecal calprotectin
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2 YEARS
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SCORES AND COST
Time Frame: 2 YEARS
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direct medical costs, work productivity and activity index, short IBDQ
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2 YEARS
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Collaborators and Investigators
Publications and helpful links
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 (Estimate)
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
- Intestinal Diseases
- Inflammatory Bowel Diseases
- Crohn Disease
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gastrointestinal Agents
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Methotrexate
- Infliximab
- Mercaptopurine
- Azathioprine
Other Study ID Numbers
- GETAID 2014-03
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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.
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