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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)

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ClinicalTrials.gov Identifier: NCT02177071
Recruitment Status : Recruiting
First Posted : June 27, 2014
Last Update Posted : January 7, 2019
Sponsor:
Collaborator:
Saint-Louis Hospital, Paris, France
Information provided by (Responsible Party):
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

Brief Summary:

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


Condition or disease Intervention/treatment Phase
Crohn's Disease Drug: INFLIXIMAB Drug: AZATHIOPRINE Drug: MERCAPTOPURINE Drug: Methotrexate Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 2015
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease
Drug Information available for: Infliximab

Arm Intervention/treatment
No Intervention: INFLIXIMAB AND ANTI METABOLITE
continuing scheduled infliximab treatment and anti-metabolite
STOP INFLIXIMAB CONTINUING ANTI METABOLITE
discontinuing infliximab and continuing the anti-metabolite
Drug: INFLIXIMAB
CONTINUING INFLIXIMAB AND discontinuing anti-metabolites
CONTINUING INFLIXIMAB AND DISCONTINUING ANTI METABOLITE
Drug: AZATHIOPRINE
Drug: MERCAPTOPURINE
Drug: Methotrexate



Primary Outcome Measures :
  1. co-primary efficacy end points [ Time Frame: 2 ans ]

    There will be two co-primary efficacy end points

    Relapse rate at 2 years, relapse being defined by either one of the following events:

    • A CDAI>250 at any visit or between 150 and 250 with an increase of at least 70 points, over two consecutive visits one week apart associated with a CRP > 5 mg/l or a fecal calprotectin > 250 microg/g
    • A new opening fistula, perianal or entero-cutaneous.
    • An intra-abdominal abcess (size of at least 3 cm) or perianal abcess (size of at least 2 cm)
    • An episode of intestinal obstruction due to Crohn's lesions confirmed by medical imaging and requiring hospitalisation (also considered as treatment failure, see below)

    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.



Secondary Outcome Measures :
  1. relapse in each arm. [ Time Frame: 2 years ]
    • Time to relapse in each arm.
    • Factors associated with time to relapse.
    • Time to relapse according to CRP and calprotectin value measured every 2 months over the follow up.

  2. Sustained clinical remission [ Time Frame: 2years ]
    Sustained clinical remission defined by CDAI<150 without steroids over two years.

  3. Treatment failure [ Time Frame: 2 years ]
    • Treatment failure rate. Treatment failure is defined by not achieving remission after treatment adaptation following a relapse according to protocol (CDAI<150 or, in case of relapse defined by the occurence of a new fistula, the absence of fistula closure). The occurence of an intra-abdominal or peri-anal abcess and the occurence of an intestinal obstruction due to Crohn's lesions and requiring a surgical resection or an endoscopic dilatation are also directly considered as treatment failure and will not be managed by treatment adaptation according to protocol.
    • Time to treatment failure.

  4. Tissue damage progression [ Time Frame: 2 years ]
    - Tissue damage progression will be assessed by the Lémann Score absolute and relative change between baseline and en of the study (2 years).


Other Outcome Measures:
  1. disability index [ Time Frame: 2 YEARS ]
    disability index

  2. adverse events and SAE [ Time Frame: 2 YEARS ]
    adverse events and SAE, events related to re-infusions,

  3. BIOLOGICS [ Time Frame: 2 YEARS ]
    trough levels of infliximab, ATI , hsCRP, fecal calprotectin

  4. SCORES AND COST [ Time Frame: 2 YEARS ]
    direct medical costs, work productivity and activity index, short IBDQ



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02177071


Contacts
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Contact: Edouard LOUIS, PHD 0033142494988 edouard.louis@ulg.ac.be

Locations
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Australia
St Vincent Hospital Recruiting
Melbourne, Australia
Contact: NIK DONG, MD       Nik.DING@svha.org.au   
Contact: Kylie Parker       kylie.PARKER@svha.org.au   
Principal Investigator: NIK DONG         
Belgium
Gent University Hospital Recruiting
Gent, Belgium, 9000
Contact: Martine DE VOS, MD,PhD    003292402371    martine.devos@uzgent.be   
Principal Investigator: Martine DE VOS, MD,PhD         
CHU LIEGE - Sart Tilman Recruiting
Liege, Belgium, 4000
Contact: Edouard LOUIS, MD,PhD    +32436667889    Edouard.Louis@ulg.ac.be   
Contact: Sylvie WERTZ    +32 4 366 74 39    swertz@chu.ulg.ac.be   
Sub-Investigator: EDOUARD LOUIS, MD         
France
Chu Amiens Recruiting
Amiens, France, 80054
Contact: Jean-Louis DUPAS, MD,PhD    +33 3 22 66 82 08    dupas.jean-louis@chu-amiens.fr   
Contact: Martine LECONTE    +33 3 22 66 82 14      
Principal Investigator: JEAN LOUIS DUPAS, MD         
Chu Besancon Recruiting
Besancon, France, 25030
Contact: LUCINE VUITON, MD         
Principal Investigator: LUCINE VUITON, MD         
Sub-Investigator: STEPHANE KOCH, MD         
Caen Unversity Hospital Recruiting
Caen, France, 14033
Sub-Investigator: STEPHANIE VIENNOT, MD         
Chu Clermont-Ferrand Recruiting
Clermont-ferrand, France, 63003
Contact: Gilles BOMMELAER, MD,PhD    +33473750523    gbommelaer@chu-clermontferrand.fr   
Sub-Investigator: Gilles BOMMELAER, MD,PhD         
Sub-Investigator: ANTONY BUISSON, MD         
Hopital Beaujon Recruiting
Clichy, France, 92110
Contact: Yoram BOUHNIK, MD,PhD    +33 1 40 87 56 00    yoram.bouhnik@bjn.aphp.fr   
Principal Investigator: YORAM BOUHNIK, MD,PhD         
Sub-Investigator: Alain ATTAR, MD         
Sub-Investigator: Carmen STEFANESCU, MD         
Sub-Investigator: Xavier TRETON, MD         
Hopital Henri Mondor Not yet recruiting
Creteil, France, 94010
Contact: Jean-Charles DELCHIER, MD,PhD    +33149812351    jean-charles.delchier@hmn.aphp.fr   
Principal Investigator: Jean-Charles DELCHIER, MD,PhD         
Sub-Investigator: Aurelien AMIOT, MD         
Chu Kremlin Bicetre Recruiting
Kremlin Bicetre, France
Sub-Investigator: FRANCK CARBONNEL, MD         
Hopital Bicetre Recruiting
Le Kremlin Bicetre, France, 94275
Contact: Franck CARBONNEL, MD,PhD    +33 1 45 21 37 22    franck.carbonnel@bct.aphp.fr   
Principal Investigator: Franck CARBONNEL, MD,PhD         
Chu Lille Recruiting
Lille, France
Contact: Maria NACHURY, MD         
Principal Investigator: Maria NACHURY, MD         
Ch Le Raincy Montfermeil Withdrawn
Montfermeil, France, 93370
Chu Montpellier Not yet recruiting
Montpellier, France, 34295
Contact: ROMAIN ALTWEGG, MD    +33467337394      
Sub-Investigator: ROMAIN ALTWEGG, MD         
Principal Investigator: GUILLAUME PINETON DE CHAMBRUN, MD         
Chu Nantes Recruiting
Nantes, France, 44093
Contact: Arnaud BOURREILLE, MD    +33202400830    arnaud.boureille@chu-nantes.fr   
Principal Investigator: Arnaud BOURREILLE, MD         
Sub-Investigator: Mathurin FLAMANT, MD         
CHU NICE Recruiting
Nice, France, 06202
Contact: Xavier HEBUTERNE, MD,PhD    +33492066168    hebuterne.x@chu-nice.fr   
Principal Investigator: Xavier HEBUTERNE, MD,PhD         
Sub-Investigator: Jérome FILIPPI, MD         
Hopital Saint Louis Recruiting
Paris, France, 75010
Contact: Matthieu ALLEZ, MD, PhD    33 1 42 49 95 97    matthieu.allez@sls.aphp.fr   
Principal Investigator: Mathieu ALLEZ, MD, PhD         
Sub-Investigator: Jean-Marc GORNET, MD         
Sub-Investigator: Clotilde BAUDRY, MD         
Sub-Investigator: Joelle BONNET, MD         
Hopital St Antoine Recruiting
Paris, France, 75012
Contact: Jacques COSNES, MD, PhD    +33 1 49 28 31 70    jacques.cosnes@sat.aphp.fr   
Sub-Investigator: Philippe SEKSIK, MD         
Principal Investigator: Laurent BEAUGERIE, MD, PhD         
Hopital Cochin Not yet recruiting
Paris, France, 75014
Contact: Vered ABITBOL, MD    +33158411967    vered@club-internet.fr   
Sub-Investigator: Stanislas CHAUSSADE, MD,PhD         
Principal Investigator: Vered ABITBOL, MD         
Hopital Saint Joseph Recruiting
Paris, France, 75014
Contact: ELISE CHANTELOUP, MD       echanteloup@hpsj.fr   
Principal Investigator: ELISE CHANTELOUP, MD         
Montsouris Mutualist Institute Recruiting
Paris, France, 75674
Sub-Investigator: ANTOINE BLAIN, MD         
Sub-Investigator: Marion SIMON, MD         
CHU Bordeaux - Pessac Recruiting
Pessac, France, 33700
Contact: David LAHARIE, MD       david.laharie@chu-bordeaux.fr   
Contact: Sylvie RAZAIRE       sylvie.razaire@chu-bordeaux.fr   
Principal Investigator: David LAHARIE, MD         
CHU LYON Recruiting
Pierre Benite, France, 69495
Contact: Bernard FLOURIE, MD,PhD    +33478861288    bernard.flourie@chu-lyon.fr   
Principal Investigator: Bernard FLOURIE, MD,PhD         
Sub-Investigator: Stéphane NANCEY, MD         
Chu Reims Active, not recruiting
Reims, France
Chu Rennes Recruiting
Rennes, France, 35033
Contact: Guillaume BOUGUEN, MD    +33299284347    guillaume.bouguen@chu-rennes.fr   
Sub-Investigator: Laurent SIPROUDHIS, MD,PhD         
Principal Investigator: GUILLAUME BOUGUEN, MD         
Chu Rouen Not yet recruiting
Rouen, France, 76031
Contact: Eric LEREBOURS, MD,PhD    +33232888101    eric.lerebours@chu-rouen.fr   
Principal Investigator: Eric LEREBOURS, MD,PhD         
Sub-Investigator: Guillaume SAVOYE, MD         
Chu Saint Etienne Recruiting
St Etienne, France, 42270
Contact: Xavier ROBLIN, MD    +33 4 77 82 83 20    xavier.roblin@chu-st-etienne.fr   
Principal Investigator: Xavier ROBLIN, MD         
Chu Strasbourg Withdrawn
Strasbourg, France, 67091
Chu Toulouse Recruiting
Toulouse, France, 31403
Contact: Jacques MOREAU, MD    +33561322764    moreau.j@chu-toulouse.fr   
Principal Investigator: Jacques MOREAU, MD         
Ch Gustave Dron Withdrawn
Tourcoing, France, 59208
Chu Tours Recruiting
Tours, France, 37044
Contact: Laurence PICON, MD    +33247475916    l.picon@chu-tours.fr   
Sub-Investigator: Laurence PICON, MD         
Principal Investigator: Alexandre AUBOURG, MD         
Chr Valencienne Not yet recruiting
Valencienne, France, 59300
Contact: MEDINA BOUALIT, MD         
Principal Investigator: MEDINA BOUALIT, MD         
Chu Nancy Recruiting
Vandoeuvre Les Nancy, France, 54500
Contact: LAURENT PEYRIN BIROULET, MD,PhD    +33383153354      
Principal Investigator: Laurent PEYRIN-BIROULET, MD,PhD         
Sponsors and Collaborators
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Saint-Louis Hospital, Paris, France
Investigators
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Principal Investigator: Benjamin PARIENTE, doctor Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

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Responsible Party: Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
ClinicalTrials.gov Identifier: NCT02177071     History of Changes
Other Study ID Numbers: GETAID 2014-03
First Posted: June 27, 2014    Key Record Dates
Last Update Posted: January 7, 2019
Last Verified: January 2019
Keywords provided by Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives:
CROHN DISEASE
INFLIXIMAB
COMBINATION THERAPY
steroid free remission
anti-metabolites
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Methotrexate
Azathioprine
Mercaptopurine
Infliximab
Antimetabolites
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Gastrointestinal Agents