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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02177071




Registration number
NCT02177071
Ethics application status
Date submitted
26/06/2014
Date registered
27/06/2014
Date last updated
9/03/2020

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
GETAID 2014-03
Universal Trial Number (UTN)
Trial acronym
SPARE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn's Disease 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Crohn's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - INFLIXIMAB
Treatment: Drugs - AZATHIOPRINE
Treatment: Drugs - MERCAPTOPURINE
Treatment: Drugs - Methotrexate

No Intervention: INFLIXIMAB AND ANTI METABOLITE - continuing scheduled infliximab treatment and anti-metabolite

Other: STOP INFLIXIMAB CONTINUING ANTI METABOLITE - discontinuing infliximab and continuing the anti-metabolite

Other: CONTINUING INFLIXIMAB AND discontinuing anti-metabolites - CONTINUING INFLIXIMAB AND DISCONTINUING ANTI METABOLITE


Treatment: Drugs: INFLIXIMAB


Treatment: Drugs: AZATHIOPRINE


Treatment: Drugs: MERCAPTOPURINE


Treatment: Drugs: Methotrexate


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
2 ans
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
Sustained clinical remission - Sustained clinical remission defined by CDAI<150 without steroids over two years.
Timepoint [2] 0 0
2years
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
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).
Timepoint [4] 0 0
2 years
Secondary outcome [5] 0 0
Endoscopic remission - Endoscopic remission at the end of study
Timepoint [5] 0 0
2 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St Vincent Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Province De Liège
Country [2] 0 0
Belgium
State/province [2] 0 0
Gent
Country [3] 0 0
France
State/province [3] 0 0
Auvergne Rhone Alpes
Country [4] 0 0
France
State/province [4] 0 0
Bourgogne-Franche-Comte
Country [5] 0 0
France
State/province [5] 0 0
Bretagne
Country [6] 0 0
France
State/province [6] 0 0
Centre Val De Loire
Country [7] 0 0
France
State/province [7] 0 0
Grand Est
Country [8] 0 0
France
State/province [8] 0 0
Hauts De France
Country [9] 0 0
France
State/province [9] 0 0
Ile De France
Country [10] 0 0
France
State/province [10] 0 0
Normandie
Country [11] 0 0
France
State/province [11] 0 0
Nouvelle-aquitaine
Country [12] 0 0
France
State/province [12] 0 0
Occitanie
Country [13] 0 0
France
State/province [13] 0 0
Pays De La Loire
Country [14] 0 0
France
State/province [14] 0 0
Provences Alpes Cote d'Azur
Country [15] 0 0
France
State/province [15] 0 0
Paris

Funding & Sponsors
Primary sponsor type
Other
Name
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Saint-Louis Hospital, Paris, France
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT02177071
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Benjamin PARIENTE, doctor
Address 0 0
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications