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

Colitis,Ulcerative Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03011268
• Other study ID #: HMR2016-0.6
• Secondary ID: 2016-001409-18
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 9, 2017
• Est. completion date: February 1, 2025

Study information

• Verified date: June 2024
• Source: Helse Møre og Romsdal HF
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 174
• Est. completion date: February 1, 2025
• Est. primary completion date: February 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Colitis,Ulcerative
• Necrosis
• Ulcer

Intervention

Other:
• Discontinuation of anti-TNF treatment
Discontinuation of treatment with Infliximab, Adalimumab, and Golimumab in order to record time to relapse occurrences
• Continuation of anti-TNF treatment
Continuation of treatment with Infliximab, Adalimumab, and Golimumab for 2 years after randomization, then discontinue

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Helse Møre og Romsdal HF	Oslo University Hospital, University of Oslo

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	2 years
Secondary	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	4 years
Secondary	Time from randomization to relapse	Relapse time	2 years
Secondary	Time from randomization to relapse	Relapse time	4 years
Secondary	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	2 years
Secondary	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	4 years
Secondary	Proportion of relapse patients achieving remission after anti-TNF restart	Remission after relapse	2 years
Secondary	Proportion of relapse patients achieving remission after anti-TNF restart	Remission after relapse	4 years
Secondary	Adverse events and serious adverse events frequency and severity	Adverse events	2 years
Secondary	Adverse events and serious adverse events frequency and severity	Adverse events	4 years