GIS-SUSANTI-TNF-2015 (Anti-TNF Discontinuation )

Sponsor

Fundación de Investigación Biomédica - Hospital Universitario de La Princesa (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02994836

Collaborator

(none)

194

Enrollment

Location

Arms

68.3

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will be a multicentre prospective randomized trial to assess the percentage of patients with IBD who, after stopping anti-TNF treatment, have sustained clinical remission at one year compared to those in which the treatment is continued at stable doses

Condition or Disease	Intervention/Treatment	Phase
Crohn's Disease Inflammatory Bowel Disease Ulcerative Colitis	Biological: Anti-TNF: Infliximab (Infusion) Drug: Anti-TNF discontinuation: Physiological saline solution Biological: Anti-TNF:Adalimumab (Subcutaneus) Drug: Anti-TNF discontinuation: Physiological saline solution	Phase 4

Detailed Description

A multicentre prospective randomized trial.

Hypothesis:

The discontinuation of anti-TNF treatment in inflammatory bowel disease (IBD) patients in clinical remission is associated with an increased risk of recurrence compared with maintaining such treatment.

Main objective:

To assess the percentage of patients with IBD who, after stopping anti-TNF treatment, have sustained clinical remission at one year compared to those in which the treatment is continued at stable doses

Secondary objectives:

To compare treatment discontinuation vs. treatment continuation of anti-TNF agents in patients with Crohn´s disease or ulcerative colitis in terms of:

remission (relapse-free) time,
phenotype changes with both strategies
mucosal healing,
radiologic healing
impact on quality of life and productivity
safety
to identify relapse predictive factors.
To identify relapse predictive factors after anti-TNF drug discontinuation
Determining the profile of serum cytokines in patients with both strategies, depending on drug exposure and if maintained clinical remission or relapse.

Planned number of subject to be included: 194

The participation of at 50 hospitals in Spain with an inclusion of about 5 patients per hospital is required..

Case report Form was designed on REDCap (a free, secure, web-based application designed to support data capture for research studies).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

194 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: Multicentre, Prospective, Randomized Clinical Trial and Economic Evaluation

Actual Study Start Date :

Apr 21, 2017

Actual Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Anti-TNF Infliximab (Infusion 5mg/kg milligram(s)/Kilogram-Intravenous use) or Adalimumab (Subcutaneus 40 mg milligram(s)-subcutaneus)	Biological: Anti-TNF: Infliximab (Infusion) Infliximab (Infusion 5mg/kg milligram(s)/Kilogram-Intravenous use)(Visit1,visit 3,visit 4,visit 5, visit 6 and visit 7) Biological: Anti-TNF:Adalimumab (Subcutaneus) Adalimumab (Subcutaneus 40 mg milligram(s)-subcutaneus)(Visit 1,visit 2,visit 3,visit 4,visit 5, visit 6 and visit 7).
Placebo Comparator: Anti-TNF discontinuation (Placebo) Physiological saline solution (Infusion-Intravenous use) or Physiological saline solution (Injection-subcutaneous use)	Drug: Anti-TNF discontinuation: Physiological saline solution Physiological saline solution (Infusion-Intravenous use)(Visit1,visit 3,visit 4,visit 5, visit 6 and visit 7) Drug: Anti-TNF discontinuation: Physiological saline solution Physiological saline solution (Injection-subcutaneous use)(Visit 1,visit 2,visit 3,visit 4,visit 5, visit 6 and visit 7).

Arm

Intervention/Treatment

Active Comparator: Anti-TNF

Infliximab (Infusion 5mg/kg milligram(s)/Kilogram-Intravenous use) or Adalimumab (Subcutaneus 40 mg milligram(s)-subcutaneus)

Biological: Anti-TNF: Infliximab (Infusion)

Infliximab (Infusion 5mg/kg milligram(s)/Kilogram-Intravenous use)(Visit1,visit 3,visit 4,visit 5, visit 6 and visit 7)

Biological: Anti-TNF:Adalimumab (Subcutaneus)

Adalimumab (Subcutaneus 40 mg milligram(s)-subcutaneus)(Visit 1,visit 2,visit 3,visit 4,visit 5, visit 6 and visit 7).

Placebo Comparator: Anti-TNF discontinuation (Placebo)

Physiological saline solution (Infusion-Intravenous use) or Physiological saline solution (Injection-subcutaneous use)

Drug: Anti-TNF discontinuation: Physiological saline solution

Physiological saline solution (Infusion-Intravenous use)(Visit1,visit 3,visit 4,visit 5, visit 6 and visit 7)

Drug: Anti-TNF discontinuation: Physiological saline solution

Physiological saline solution (Injection-subcutaneous use)(Visit 1,visit 2,visit 3,visit 4,visit 5, visit 6 and visit 7).

Outcome Measures

Primary Outcome Measures

Sustained clinical remission after one year of follow-up (after discontinuing or continuing treatment with anti-TNF). [Change at 12 months.]

Secondary Outcome Measures

Clinical activity assessment [Month 0, month 1, month 2, month 4, month 6, month 8, month 10, month 12]
On Crohn´s Disease: Measure by Crohn´s Disease Activity Index (CDAI)
Endoscopic activity assessment [12 Months. On the Month 0, month 12 or relapse]
On Crohn´s Disease: Measure by Simplified endoscopic activity score for Crohn´s disease (SES-CD).
Radiologic activity assessment [12 Months. Month 0, month 12 or relapse]
Measure by absence of contrast enhancement, edema or presence of ulcers
Quality of life assessment [Month 0, month 1, month 2, month 4, month 6, month 8, month 10, month 12]
Measure by the Inflammatory Bowel Disease Questionnaire (IBDQ-9)
The Work productivity and activity assessment [Month 0, month 1, month 2, month 4, month 6, month 8, month 10, month 12]
Measure by "Spanish Work Productivity and Activity Impairment Questionnaire".This questionnaire assessments the sum of work time missed because IBD and impairment while working yields the overall work impairment (productivity loss) score. Scores are expressed as percentages of impairment/productivity loss, with higher scores indicating greater impairment.
Clinical activity assessment [Month 0, month 1, month 2, month 4, month 6, month 8, month 10, month 12]
On the Ulcerative Colitis disease: Measure by Mayo Scoring System
Endoscopic activity assessment [12 Months. On the Month 0, month 12 or relapse]
On the Ulcerative Colitis disease: Measure by Mayo endoscopic score.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients diagnosed with IBD by the usual criteria; both Crohn's and ulcerative colitis disease.
Patients older than 18 years.
In the case of patients with Crohn's disease the indication treatment with anti-TNF it must have been for luminal involvement (no perianal).
Are currently in clinical remission.
The clinical remission period with the drug at non-intensified dose it must have been at least 6 months.

The administration of ≥10 mg/kg/8 weeks or 5 mg / kg / ≤ 4 weeks, in the case of infliximab, and 40 mg / week, in the case of adalimumab, is considered an intensified dose.

At the time of inclusion, the patient should be receiving concomitant immunosuppressants (thiopurine or methotrexate) to anti-TNF treatment, and must have received these immunosuppressive drugs at stable doses for at least the last 3 months.
In patients with Crohn's disease or ulcerative colitis disease, at baseline colonoscopy (made up to 3 months prior to the screening visit) should not be "significant" injuries.
In the case of patients with Crohn's ileal or ileocolic disease, in magnetic resonance whole should not be "significant" injuries.(made up to 3 months prior to the screening visit)

Exclusion Criteria:

Age less than 18 years.
Patients who have been treated with anti-TNF for other indication than the IBD.
Patients with Crohn's disease in which the indication for treatment with anti-TNF has been the perianal involvement (or luminal and perianal both); or showing active perianal disease at the time of inclusion.
Patients who are not receiving concomitant treatment with immunosuppressants (thiopurine or methotrexate) at the moment (and in the previous 3 months).
Patients undergoing bowel resection surgery; therefore, patients who began anti-TNF therapy to prevent or treat postoperative recurrence in Crohn's disease will be excluded.
Presence of "significant" endoscopic or radiological lesions
Advanced chronic illness or any other condition that prevents the patient from coming to the clinic for monitoring or follow-up.
Patients who are pregnant, breastfeeding or intending to become pregnant during the course of the study.
Refusal to give consent for participation in the study.