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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02994836
Recruitment Status : Active, not recruiting
First Posted : December 16, 2016
Last Update Posted : January 15, 2021
Sponsor:
Information provided by (Responsible Party):
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Study Description
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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) 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:

  1. remission (relapse-free) time,
  2. phenotype changes with both strategies
  3. mucosal healing,
  4. radiologic healing
  5. impact on quality of life and productivity
  6. safety
  7. to identify relapse predictive factors.
  8. To identify relapse predictive factors after anti-TNF drug discontinuation
  9. 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
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Study Type : Interventional  (Clinical Trial)
Estimated 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 : April 21, 2017
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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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
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Primary Outcome Measures :
  1. Sustained clinical remission after one year of follow-up (after discontinuing or continuing treatment with anti-TNF). [ Time Frame: Change at 12 months. ]

Secondary Outcome Measures :
  1. Clinical activity assessment [ Time Frame: 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)

  2. Endoscopic activity assessment [ Time Frame: 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).

  3. Radiologic activity assessment [ Time Frame: 12 Months. Month 0, month 12 or relapse ]
    Measure by absence of contrast enhancement, edema or presence of ulcers

  4. Quality of life assessment [ Time Frame: 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)

  5. The Work productivity and activity assessment [ Time Frame: 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.

  6. Clinical activity assessment [ Time Frame: 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

  7. Endoscopic activity assessment [ Time Frame: 12 Months. On the Month 0, month 12 or relapse ]
    On the Ulcerative Colitis disease: Measure by Mayo endoscopic score.


Eligibility Criteria
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Information from the National Library of Medicine

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

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.
Contacts and Locations
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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): NCT02994836


Locations
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Spain
Hospital Universitario de La Princesa
Madrid, Spain, 28006
Sponsors and Collaborators
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Investigators
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Principal Investigator: Javier MD Perez Gisbert, PhD Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
More Information
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Publications:
Bortlík M, Ďuricová D, Lukáš M, Malíčková K, Machková N, Hrdlička L, et al. Infliximab trough levels at treatment discontinuation are associated with increased risk of disease relapse in patients with inflammatory bowel diseases. 20th United European Gastroenterology Week. 2012:P0870.
Echarri A, Ollero V, Gallego C, Porta A, Castro J. Anti-TNF withdrawal in IBD patients on deep remission. Risk factors of relapse. 20th United European Gastroenterology Week. 2012:P0287.
Ciria V, Silva P, Leo E, Trigo C, De la Cruz MD, Herrera JM, et al. Factors influencing recurrence following suspension of biological treatment. Importance of mucosal healing. J Crohns Colitis. 2014;8 (suppl.1):P487.
Ramos L, Hernandez A, Carrillo M, Alonso I, Hernandez N, Quintero E. Outcome of treatment with biological agents in Crohn's disease: 117 patients in 5 years from a tertiary referral center. J Crohns Colitis. 2014;8 (suppl.1):P398.
Luppino I, Spagnuolo R, Marasco R, Cosco C, Ruggiero G, Cosco V, et al. Withdrawal of infliximab (IFX) after achieving remission: outcome in a cohort of inflammatory bowel disease (IBD) patients. Dig Liver Dis. [Conference abstract: Abstracts of the 19th National Congress of Digestive Diseases]. 2013;45S:S100-S1.
Marino M, Zucchi E, Fabbro M, Lodolo I, Maieron R, Vadalà S, et al. Outcome of infliximab discontinuation in IBD patients and therapy rechallenging in relapsers: Single centre preliminary data. J Crohns Colitis. 2014;8 (suppl.1):P401.
Annunziata ML, Papparella LG, Sansoni I, Balestrieri P, Cicala M. Normalized wall thickness at MRE predicts clinical remission in Crohn's disease after infliximab discontinuation: a 5 years follow-up. J Crohns Colitis. 2014;8 (suppl.1):P402.
Nuti F, Conte F, Cavallari N, Civitelli F, Aloi M, Alessandri C, et al. Long term efficacy of infliximab in inflammatory bowel disease at a single tertiary center. Dig Liver Dis. [Congress comunication: 17th National Congress SIGENP]. 2010;42(SUPPL. 5):S326-S7.
Armuzzi A, Marzo M, Felice C, De Vincentis F, Andrisani G, Moccio G, et al. Long-term scheduled therapy with infliximab in inflammatory bowel disease: a single-centre observational study. Gastroenterology. 2010;238 (suppl.1):S-691.
Muñoz C, Bravo MT, Ortiz de Zárate J, Arreba P, García I, Heras J, et al. Mucosal healing in patients with ulcerative colitis treated with infliximab. What happens after treatment is discontinued? J Crohns Colitis. 2014;8 (suppl.1):P405.
Casanova MJ, Chaparro M, García-Sánchez V, Nantes O, Jauregui-Amezaga A, Rojas-Feria M, et al. Evolution after anti-TNF drug discontinuation in patients with inflammatory bowel disease (IBD): a multicenter long-term follow-up study. J Crohns Colitis. 2015;9 (suppl.1):S329.
Felice C, Pugliese D, Guidi L, Marzo M, Andrisani G, Papa A, et al. Retreatment with infliximab in inflammatory bowel disease: tolerability and effectiveness of different re-induction regimens. J Crohns Colitis. 2014;8 (suppl.1):P363

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Responsible Party: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
ClinicalTrials.gov Identifier: NCT02994836    
Other Study ID Numbers: GIS-SUSANTI-TNF-2015
First Posted: December 16, 2016    Key Record Dates
Last Update Posted: January 15, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundación de Investigación Biomédica - Hospital Universitario de La Princesa:
Crohn's Disease
Inflammatory bowel disease
Anti-TNF discontinuation
Ulcerative colitis
Additional relevant MeSH terms:
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Crohn Disease
Colitis
Colitis, Ulcerative
Intestinal Diseases
Inflammatory Bowel Diseases
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
 Colonic Diseases
Pathologic Processes
Adalimumab
Infliximab
Pharmaceutical Solutions
Anti-Inflammatory Agents
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents