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Anti-tumor Necrosis Factor in Patients With Ulcerative Colitis in Clinical Remission: to Continue or Not? (BIOSTOP)

Primary Purpose

Colitis,Ulcerative

Status
Active
Phase
Not Applicable
Locations
Norway
Study Type
Interventional
Intervention
Discontinuation of anti-TNF treatment
Continuation of anti-TNF treatment
Sponsored by
Helse Møre og Romsdal HF
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colitis,Ulcerative focused on measuring Tumor Necrosis Factor-alpha/antagonists & inhibitors, Infliximab, Adalimumab, Golimumab, Recurrence

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • confirmed diagnosis of ulcerative colitis
  • treated for minimum 1 year with first-line anti-tumor necrosis factor (TNF) treatment
  • in sustained clinical remission during the last 3 months
  • capable of understanding and signing an informed consent form

Exclusion Criteria:

  • Discontinuation of systemic 5-Aminosalicylic acid (ASA) or immunomodulatory therapy or other medication that could affect disease activity during the last 3 months prior to randomization
  • Any treatment of systemic corticosteroids due to disease exacerbation during the last 3 months (i.e. patients being in steroid free clinical remission)
  • Patients on anti-TNF monotherapy with intolerance to both 5-ASA and immunomodulatory therapy
  • Change in the anti-TNF treatment during the last 3 months due to disease related factors, not including dose/frequency adjustments due to drug concentration measurements
  • Use of any second-line anti-TNF medication irrespective of reason for stopping first-line anti-TNF
  • Previous failed attempts of anti-TNF discontinuation of more than 4 months' duration, with the exception of discontinuation due to pregnancy
  • Detection of anti-TNF antibodies in moderate-high titers prior to randomization
  • Psychiatric or mental disorders
  • Alcohol abuse or other substance abuse
  • language barriers or other factors which makes adherence to the study protocol impossible
  • Participation in any other studies
  • pregnancy
  • breastfeeding

Sites / Locations

  • Helse Møre og Romsdal, Ålesund Sjukehus
  • Haraldsplass Diakonale sykehus
  • Haukeland Universitetssykehus Helse Bergen HF
  • Helse Førde, Førde Sentralsjukehus
  • Sykehuset Østfold HF Kalnes
  • Sykehuset Innlandet, Hamar Sykehus
  • Universitetssykehuset i Nord-Norge, Harstad
  • Sørlandet Sykehus HF, Kristiansand
  • Helse Møre og Romsdal, Kristiansund Sjukehus
  • Helse Nord Trøndelag, Levanger Sykehus
  • Akershus Universitetssykehus, Lørenskog
  • Oslo Universitetssykehus, Rikshospitalet
  • Oslo Universitetssykehus, Ullevål
  • Vestre Viken HF, Bærum Sykehus
  • Sykehuset Telemark, Skien
  • Stavanger Universitetssykehus
  • Sykehuset Vestfold, Tønsberg
  • Helse Møre og Romsdal, Volda Sjukehus
  • Helse Bergen HF Voss Sjukehus

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Anti TNF discontinuation

Anti TNF continuation

Arm Description

Discontinuation of anti-TNF treatment (Infliximab, Adalimumab, Golimumab)

Continuation of anti-TNF treatment (Infliximab, Adalimumab, Golimumab)

Outcomes

Primary Outcome Measures

Proportion of patients in sustained clinical remission
Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 2 years of randomized treatment

Secondary Outcome Measures

Proportion of patients in sustained clinical remission
Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 4 years of randomized treatment
Time from randomization to relapse
Relapse time
Time from randomization to relapse
Relapse time
Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy
Remission, but no need to restart anti-tnf therapy
Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy
Remission, but no need to restart anti-tnf therapy
Proportion of relapse patients achieving remission after anti-TNF restart
Remission after relapse
Proportion of relapse patients achieving remission after anti-TNF restart
Remission after relapse
Adverse events and serious adverse events frequency and severity
Adverse events
Adverse events and serious adverse events frequency and severity
Adverse events

Full Information

First Posted
January 2, 2017
Last Updated
March 16, 2023
Sponsor
Helse Møre og Romsdal HF
Collaborators
Oslo University Hospital, University of Oslo
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1. Study Identification

Unique Protocol Identification Number
NCT03011268
Brief Title
Anti-tumor Necrosis Factor in Patients With Ulcerative Colitis in Clinical Remission: to Continue or Not?
Acronym
BIOSTOP
Official Title
Continuing or Discontinuing Anti-tumor Necrosis Factor Treatment in Patients With Ulcerative Colitis in Clinical Remission: a Prospective Open Randomized Parallel-group Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 9, 2017 (Actual)
Primary Completion Date
February 1, 2023 (Actual)
Study Completion Date
February 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Helse Møre og Romsdal HF
Collaborators
Oslo University Hospital, University of Oslo

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective is to assess if discontinuation of anti- tumor necrosis factor alpha (TNF) treatment in ulcerative colitis patients in sustained clinical remission, with the option to restart treatment in the case of relapse, is non-inferior to continued anti-TNF treatment. Secondary objectives are to assess the efficacy and safety of restarting anti-TNF treatment after a relapse
Detailed Description
The BIOSTOP study is a prospective, open randomized, multicenter, parallel-group study to compare clinical outcome of discontinuing (interventional group) compared to continuing (control group) biologic treatment with anti-TNF in ulcerative colitis patients in clinical remission. Adult male and female patients with an established diagnosis of ulcerative colitis treated for minimum one year with anti-TNF maintenance therapy and being in clinical remission during the last 3 months are potential study patients. Eligible patients who have given their informed written consent will be randomized 1:1 to either discontinue anti-TNF treatment or to continue anti-TNF treatment for another two years. Patients in the control group who are still in clinical and endoscopic remission after two years on continued anti-TNF treatment, will then be switched to discontinue anti-TNF treatment. End of study/follow-up is after 4 years. In order to identify the primary endpoint (occurrence of disease relapse), each study center will have a phone number for patients to call in case of symptoms suspect of increased disease activity. If a patient is experiencing a potential disease flare (6-point Mayo score > 1) and/or 2 consecutive calprotectin tests are positive (> 200 mg/kg), an unscheduled visit including recto sigmoidoscopy will be performed without delay to document disease status. 150 participants enrolled, September 2020 Covid 19 - randomization period extended until 31.12.2020

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colitis,Ulcerative
Keywords
Tumor Necrosis Factor-alpha/antagonists & inhibitors, Infliximab, Adalimumab, Golimumab, Recurrence

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
174 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Anti TNF discontinuation
Arm Type
Experimental
Arm Description
Discontinuation of anti-TNF treatment (Infliximab, Adalimumab, Golimumab)
Arm Title
Anti TNF continuation
Arm Type
Active Comparator
Arm Description
Continuation of anti-TNF treatment (Infliximab, Adalimumab, Golimumab)
Intervention Type
Other
Intervention Name(s)
Discontinuation of anti-TNF treatment
Other Intervention Name(s)
Remicade, Remsima, Inflectra, Humira, Simponi
Intervention Description
Discontinuation of treatment with Infliximab, Adalimumab, and Golimumab in order to record time to relapse occurrences
Intervention Type
Other
Intervention Name(s)
Continuation of anti-TNF treatment
Other Intervention Name(s)
Remicade, Remsima, Inflectra, Humira, Simponi
Intervention Description
Continuation of treatment with Infliximab, Adalimumab, and Golimumab for 2 years after randomization, then discontinue
Primary Outcome Measure Information:
Title
Proportion of patients in sustained clinical remission
Description
Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 2 years of randomized treatment
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Proportion of patients in sustained clinical remission
Description
Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 4 years of randomized treatment
Time Frame
4 years
Title
Time from randomization to relapse
Description
Relapse time
Time Frame
2 years
Title
Time from randomization to relapse
Description
Relapse time
Time Frame
4 years
Title
Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy
Description
Remission, but no need to restart anti-tnf therapy
Time Frame
2 years
Title
Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy
Description
Remission, but no need to restart anti-tnf therapy
Time Frame
4 years
Title
Proportion of relapse patients achieving remission after anti-TNF restart
Description
Remission after relapse
Time Frame
2 years
Title
Proportion of relapse patients achieving remission after anti-TNF restart
Description
Remission after relapse
Time Frame
4 years
Title
Adverse events and serious adverse events frequency and severity
Description
Adverse events
Time Frame
2 years
Title
Adverse events and serious adverse events frequency and severity
Description
Adverse events
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: confirmed diagnosis of ulcerative colitis treated for minimum 1 year with first-line anti-tumor necrosis factor (TNF) treatment in sustained clinical remission during the last 3 months capable of understanding and signing an informed consent form Exclusion Criteria: Discontinuation of systemic 5-Aminosalicylic acid (ASA) or immunomodulatory therapy or other medication that could affect disease activity during the last 3 months prior to randomization Any treatment of systemic corticosteroids due to disease exacerbation during the last 3 months (i.e. patients being in steroid free clinical remission) Patients on anti-TNF monotherapy with intolerance to both 5-ASA and immunomodulatory therapy Change in the anti-TNF treatment during the last 3 months due to disease related factors, not including dose/frequency adjustments due to drug concentration measurements Use of any second-line anti-TNF medication irrespective of reason for stopping first-line anti-TNF Previous failed attempts of anti-TNF discontinuation of more than 4 months' duration, with the exception of discontinuation due to pregnancy Detection of anti-TNF antibodies in moderate-high titers prior to randomization Psychiatric or mental disorders Alcohol abuse or other substance abuse language barriers or other factors which makes adherence to the study protocol impossible Participation in any other studies pregnancy breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dag Arne L Hoff, md, phd
Organizational Affiliation
Helse Møre og Romsdal Hospital Trust
Official's Role
Study Director
Facility Information:
Facility Name
Helse Møre og Romsdal, Ålesund Sjukehus
City
Alesund
Country
Norway
Facility Name
Haraldsplass Diakonale sykehus
City
Bergen
ZIP/Postal Code
5009
Country
Norway
Facility Name
Haukeland Universitetssykehus Helse Bergen HF
City
Bergen
Country
Norway
Facility Name
Helse Førde, Førde Sentralsjukehus
City
Forde
Country
Norway
Facility Name
Sykehuset Østfold HF Kalnes
City
Fredrikstad
Country
Norway
Facility Name
Sykehuset Innlandet, Hamar Sykehus
City
Hamar
Country
Norway
Facility Name
Universitetssykehuset i Nord-Norge, Harstad
City
Harstad
Country
Norway
Facility Name
Sørlandet Sykehus HF, Kristiansand
City
Kristiansand
Country
Norway
Facility Name
Helse Møre og Romsdal, Kristiansund Sjukehus
City
Kristiansund
Country
Norway
Facility Name
Helse Nord Trøndelag, Levanger Sykehus
City
Levanger
Country
Norway
Facility Name
Akershus Universitetssykehus, Lørenskog
City
Lørenskog
ZIP/Postal Code
1478
Country
Norway
Facility Name
Oslo Universitetssykehus, Rikshospitalet
City
Oslo
Country
Norway
Facility Name
Oslo Universitetssykehus, Ullevål
City
Oslo
Country
Norway
Facility Name
Vestre Viken HF, Bærum Sykehus
City
Sandvika
Country
Norway
Facility Name
Sykehuset Telemark, Skien
City
Skien
Country
Norway
Facility Name
Stavanger Universitetssykehus
City
Stavanger
Country
Norway
Facility Name
Sykehuset Vestfold, Tønsberg
City
Tonsberg
Country
Norway
Facility Name
Helse Møre og Romsdal, Volda Sjukehus
City
Volda
Country
Norway
Facility Name
Helse Bergen HF Voss Sjukehus
City
Voss
Country
Norway

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
At this time there is no such plan for IPD sharing. It might be an issue regarding material stored in the study Biobank - that will be elucidated at a later stage.

Learn more about this trial

Anti-tumor Necrosis Factor in Patients With Ulcerative Colitis in Clinical Remission: to Continue or Not?

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