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Precision Dosing of Infliximab Versus Conventional Dosing of Infliximab (PRECISION)

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ClinicalTrials.gov Identifier: NCT02453776
Recruitment Status : Unknown
Verified January 2016 by M. Lowenberg, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
Recruitment status was:  Recruiting
First Posted : May 27, 2015
Last Update Posted : January 18, 2016
Sponsor:
Information provided by (Responsible Party):
M. Lowenberg, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary:
Infliximab (IFX) is highly effective in inducing and maintaining remission in patients with inflammatory bowel disease (IBD). However, a large proportion of patients will eventually lose response to IFX. Therefore, strategies to improve the outcome of maintenance treatment with IFX are required. Retrospective analyses suggest that adjusting IFX treatment in order to achieve IFX trough levels (TL) above a well-defined therapeutic threshold will improve the outcome of IFX treatment.

Condition or disease Intervention/treatment Phase
Inflammatory Bowel Disease Drug: PRECISION dosing Infliximab Phase 4

Detailed Description:

Aim of this study is to investigate the efficacy of "precision dosing" IFX maintenance treatment in comparison with standard IFX maintenance treatment in IBD patients in clinical remission.

This study will be an open, randomized, controlled trial. Inclusion criteria: Patients aged ≥18 years with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) based on endoscopy and pathology, receiving scheduled IFX therapy for ≥14 weeks, in clinical remission based on a Harvey Bradshaw Index (HBI) score ≤4 or a Partial Mayo (PM) score ≤2, for CD and UC, respectively. Exclusion criteria: Dilatation or resectional surgury in the past year and patients with a stoma/pouch.

Patients in the intervention arm will receive individualized treatment with variable IFX dosing AND/OR intervals guided by a Bayesian pharmacokinetic model, aiming to achieve an IFX TL of 3 µg/ml. Patients in the control group will continue to receive the same IFX treatment regimen that was given prior to inclusion without dose adaptation. In the control group, treatment adjustments will only be made in case of signs of active disease, in accordance to current routine care but these patients will be considered as failures to their treatment.

Primary endpoint: Proportion of patients with sustained clinical remission (based on HBI or PM). Secondary endpoints include: annual costs of IFX treatment per patient, total annual medical costs, side effects, (sustained) biochemical remission, adverse events, quality of life, IFX trough level and IFX antibodies (with an assay allowing presence of drug).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participation will result in additional blood sampling, since IFX serum concentration will be measured every 8 weeks. All other laboratory tests can be considered as routine care. Patients in the intervention group with IFX TLs >3 will receive treatment de-escalation (interval elongation and/or dose reduction) as indicated by the Baysian model. Current evidence indicates that an IFX TL of 3 suffices. Patients in the intervention group with TLs <3 will receive treatment escalation (interval shortening and/or dose increase). We hypothesize that this will result in a higher chance of remaining in clinical remission.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Precision Dosing Versus Conventional Dosing of Infliximab Maintenance Therapy: a Randomized Controlled Multicenter Study in Patients With IBD in Clinical Remission
Study Start Date : May 2015
Estimated Primary Completion Date : April 2016
Estimated Study Completion Date : April 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Infliximab

Arm Intervention/treatment
Experimental: PRECISION dosing
Infliximab may vary between 1-10 mg/kg and the interval between 4 and 12 weeks.
Drug: PRECISION dosing Infliximab
Patients in the PRECISION dosing arm will recieve model based dosing, whereas proactive adjustments in treatment can be made by measuring the Infliximab concentration.

No Intervention: Conventional dosing of Infliximab
Infliximab 5 mg/kg every 8 or 6 weeks



Primary Outcome Measures :
  1. Sustained clinical remission for the precision dosing group vs. the conventional IFX maintenance dosing group [ Time Frame: 52 weeks ]
    Sustained clinical remission based on HBI (Crohn's disease) or PM score (Ulcerative Colitis)


Secondary Outcome Measures :
  1. Cost of IFX treatment between the two groups [ Time Frame: 52 weeks ]
    Comparing costs for treatment with IFX between the two groups

  2. Proportion of patients with antibodies against IFX [ Time Frame: 52 weeks ]
  3. Quality of life [ Time Frame: 52 weeks ]
    With a QoL questionnaire

  4. Biochemical disease activity (CRP >5mg/L and fecal calprotectin ≥50% compared to baseline, to a value of >250 ug/g) [ Time Frame: 26 weeks, 52 weeks ]
    A rise in fecal calprotectin of ≥50% compared to baseline, to a value of >250 ug/g and/or serum CRP of >5mg/L



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of CD or UC based on endoscopy and pathology
  • 18 years or older
  • Clinical remission, based on a Harvey Bradshaw Index (HBI) score ≤4 or a Partial Mayo (PM) score ≤2, for CD and UC
  • Scheduled IFX maintenance treatment, regardless of interval/dosing

Exclusion Criteria:

- Dilatation or resectional surgery because of stenotic IBD in the past year


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): NCT02453776


Contacts
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Contact: Anne S Strik, drs a.s.strik@amc.uva.nl
Contact: M Lowenberg, dr m.lowenberg@amc.uva.nl

Locations
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Netherlands
Academic Medical Center Recruiting
Amsterdam, Noord-Holland, Netherlands, 1102 AZ
Contact: Anne S Strik, drs       a.s.strik@amc.uva.nl   
Contact: Mark Lowenberg, dr       m.lowenberg@amc.uva.nl   
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
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Study Director: G D'Haens Professor gastroenterology

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Responsible Party: M. Lowenberg, dr, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT02453776     History of Changes
Other Study ID Numbers: 2014_354
First Posted: May 27, 2015    Key Record Dates
Last Update Posted: January 18, 2016
Last Verified: January 2016

Keywords provided by M. Lowenberg, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Crohns Disease
Ulcerative Colitis
Infliximab
Sustained
Remission
Inflammatory bowel disease
IBD

Additional relevant MeSH terms:
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Intestinal Diseases
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Infliximab
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents