Clinical trial NCT03011268: Anti-tumor Necrosis Factor in Patients With Ulcerative Colitis in Clinical Remission: to Continue or Not?
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
Overall status: COMPLETED
Phase: NA
Conditions: Colitis,Ulcerative
Keywords: Tumor Necrosis Factor-alpha/antagonists & inhibitors
Infliximab
Adalimumab
Golimumab
Recurrence
Lead sponsor: Helse Møre og Romsdal HF
Sponsor class: OTHER_GOV
Collaborators: name: Oslo University Hospital
name: University of Oslo
First posted: 2017-01-05
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Proportion of patients in sustained clinical remission
timeFrame: 2 years
Secondary outcomes:
measure: Proportion of patients in sustained clinical remission
timeFrame: 4 years
measure: Time from randomization to relapse
timeFrame: 2 years
measure: Time from randomization to relapse
timeFrame: 4 years
measure: Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy
timeFrame: 2 years
measure: Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy
timeFrame: 4 years
measure: Proportion of relapse patients achieving remission after anti-TNF restart
timeFrame: 2 years
measure: Proportion of relapse patients achieving remission after anti-TNF restart
timeFrame: 4 years
measure: Adverse events and serious adverse events frequency and severity
timeFrame: 2 years
measure: Adverse events and serious adverse events frequency and severity
timeFrame: 4 years
Other outcomes:
Locations:
city: Alesund
country: Norway
facility: Helse Møre og Romsdal, Ålesund Sjukehus
city: Bergen
country: Norway
facility: Haraldsplass Diakonale sykehus
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus Helse Bergen HF
city: Forde
country: Norway
facility: Helse Førde, Førde Sentralsjukehus
city: Fredrikstad
country: Norway
facility: Sykehuset Østfold HF Kalnes
city: Hamar
country: Norway
facility: Sykehuset Innlandet, Hamar Sykehus
city: Harstad
country: Norway
facility: Universitetssykehuset i Nord-Norge, Harstad
city: Kristiansand
country: Norway
facility: Sørlandet Sykehus HF, Kristiansand
city: Kristiansund
country: Norway
facility: Helse Møre og Romsdal, Kristiansund Sjukehus
city: Levanger
country: Norway
facility: Helse Nord Trøndelag, Levanger Sykehus
city: Lørenskog
country: Norway
facility: Akershus Universitetssykehus, Lørenskog
city: Oslo
country: Norway
facility: Oslo Universitetssykehus, Rikshospitalet
city: Oslo
country: Norway
facility: Oslo Universitetssykehus, Ullevål
city: Sandvika
country: Norway
facility: Vestre Viken HF, Bærum Sykehus
city: Skien
country: Norway
facility: Sykehuset Telemark, Skien
city: Stavanger
country: Norway
facility: Stavanger Universitetssykehus
city: Tonsberg
country: Norway
facility: Sykehuset Vestfold, Tønsberg
city: Volda
country: Norway
facility: Helse Møre og Romsdal, Volda Sjukehus
city: Voss
country: Norway
facility: Helse Bergen HF Voss Sjukehus
Study officials:
affiliation: Helse Møre og Romsdal Hospital Trust
name: Dag Arne L Hoff, md, phd
role: STUDY_DIRECTOR
References: