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AzTrials

Crohn's DiseasePhase 4SPARENCT02177071

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

A Phase 4 study testing INFLIXIMAB, AZATHIOPRINE and MERCAPTOPURINE in people with Crohn's Disease, run by Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives at 27 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Crohn's Disease
What is being tested?
INFLIXIMAB, AZATHIOPRINE and MERCAPTOPURINE
Could I receive a placebo?
No, everyone receives an active treatment
How many people
211 participants
Where
27 sitesin 3 countries
Study dates
9 Oct 2015to Oct 2021
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

27 sites in 3 countries.

27 sites in 3 countries

France24 sites

  • Chu Amiens

    Amiens, Hauts-de-France, 80054

  • Chu Besancon

    Besançon, Bourgogne-Franche-Comté, 25030

  • Caen Unversity Hospital

    Caen, Normandy, 14033

  • Chu Clermont-Ferrand

    Clermont-Ferrand, Auvergne-Rhône-Alpes, 63003

  • Hopital Beaujon

    Clichy, Île-de-France Region, 92110

  • Chu Kremlin Bicetre

    Le Kremlin-Bicêtre, Île-de-France Region, 94270

  • Hopital Bicetre

    Le Kremlin-Bicêtre, Île-de-France Region, 94275

  • Chu Lille

    Lille, Hauts-de-France, 59000

  • Chu Montpellier

    Montpellier, Occitanie, 34295

  • Chu Nantes

    Nantes, Pays de la Loire Region, 44093

  • CHU NICE

    Nice, Provences Alpes Cote d'Azur, 06202

  • Hopital Saint Joseph

    Paris, 75014

  • Hopital Saint Louis

    Paris, Île-de-France Region, 75010

  • Hopital St Antoine

    Paris, Île-de-France Region, 75012

  • Montsouris Mutualist Institute

    Paris, Île-de-France Region, 75674

  • CHU Bordeaux - Pessac

    Pessac, New Aquitaine, 33700

  • CHU LYON

    Pierre-Bénite, Auvergne-Rhône-Alpes, 69495

  • Chu Reims

    Reims, Grand Est, 51092

  • Chu Rennes

    Rennes, Brittany Region, 35033

  • Chu Saint Etienne

    Saint-Etienne, Auvergne-Rhône-Alpes, 42270

  • Chu Toulouse

    Toulouse, Occitanie, 31403

  • Chu Tours

    Tours, Centre-Val de Loire, 37044

  • Chr Valencienne

    Valenciennes, Hauts-de-France, 59300

  • Chu Nancy

    Vandœuvre-lès-Nancy, Grand Est, 54500

Other trials in France

Belgium2 sites

  • Gent University Hospital

    Ghent, 9000

  • CHU LIEGE - Sart Tilman

    Liège, Province De Liège, 4000

Other trials in Belgium

Australia1 site

  • St Vincent Hospital

    Melbourne

Other trials in Australia

About this study

Phase IV

Design : Prospective, open-label, randomized three-arms study

Read more

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

Read the detailed description
  1. 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
Conditions
Crohn's Disease
Being tested
INFLIXIMAB, AZATHIOPRINE, MERCAPTOPURINE, Methotrexate
Keywords
CROHN DISEASE, INFLIXIMAB, COMBINATION THERAPY, steroid free remission, anti-metabolites
Medical subject headings
Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02177071
Study groupRoleWhat they receive
INFLIXIMAB AND ANTI METABOLITENo interventioncontinuing scheduled infliximab treatment and anti-metabolite
STOP INFLIXIMAB CONTINUING ANTI METABOLITEOtherdiscontinuing infliximab and continuing the anti-metabolite
Receives: Drug: INFLIXIMAB
CONTINUING INFLIXIMAB AND discontinuing anti-metabolitesOtherCONTINUING INFLIXIMAB AND DISCONTINUING ANTI METABOLITE
Receives: Drug: AZATHIOPRINE; Drug: MERCAPTOPURINE; Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. co-primary efficacy end points

    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.

    Measured: 2 ans

Secondary outcomes (5)

  1. relapse in each arm.

    • 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.

    Measured: 2 years

  2. Sustained clinical remission

    Sustained clinical remission defined by CDAI<150 without steroids over two years.

    Measured: 2years

  3. Treatment failure

    • 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.

    Measured: 2 years

  4. Tissue damage progression

    • Tissue damage progression will be assessed by the Lémann Score absolute and relative change between baseline and en of the study (2 years).

    Measured: 2 years

  5. Endoscopic remission

    Endoscopic remission at the end of study

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2014 (estimated)
  2. Study start9 Oct 2015
  3. Primary completionJun 2021
  4. Study completionOct 2021

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
211 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02177071
Sponsor's protocol ID
GETAID 2014-03
Acronym
SPARE
Status last verified
Aug 2022
First submitted
26 Jun 2014
Last updated
3 Aug 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Pierre N, Huynh-Thu VA, Baiwir D, Mazzucchelli G, Fleron M, Trzpiot L, Eppe G, De Pauw E, Laharie D, Satsangi J, Bossuyt P, Vuitton L, Vieujean S, Colombel JF, Meuwis MA, Louis E; GETAID and the SPARE-Biocycle research group. External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn's disease stopping infliximab. Gut. 2024 Nov 11;73(12):1965-1973. doi: 10.1136/gutjnl-2024-332648.

    PubMed 39134391

  • Louis E, Resche-Rigon M, Laharie D, Satsangi J, Ding N, Siegmund B, D'Haens G, Picon L, Bossuyt P, Vuitton L, Irving P, Viennot S, Lamb CA, Pollok R, Baert F, Nachury M, Fumery M, Gilletta C, Almer S, Ben-Horin S, Bouhnik Y, Colombel JF, Hertervig E; GETAID and the SPARE-Biocycle research group. Withdrawal of infliximab or concomitant immunosuppressant therapy in patients with Crohn's disease on combination therapy (SPARE): a multicentre, open-label, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023 Mar;8(3):215-227. doi: 10.1016/S2468-1253(22)00385-5. Epub 2023 Jan 11.

    PubMed 36640794

  • Hirten RP, Lakatos PL, Halfvarson J, Colombel JF. Reply. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1301-1302. doi: 10.1016/j.cgh.2020.07.061. Epub 2020 Nov 26. No abstract available.

    PubMed 33248096

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing INFLIXIMAB, AZATHIOPRINE and MERCAPTOPURINE in people with Crohn's Disease, run by Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives at 27 sites in 3 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 10 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 3 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in France, Belgium, Australia. 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?

co-primary efficacy end points (time frame: 2 ans). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02177071, which also lists 3 linked publications.

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 3 Aug 2022.

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