The Norwegian Drug Monitoring Study

NCT03074656 | Completed

• 1 other identifier: DIA2016-1
• Study Type: interventional
• Target: 611
• Locations: 1 country
• Sites: 21

Brief Summary

Infliximab and other TNF-inhibitors have revolutionised the treatment of several immunological inflammatory diseases. Still, more than half of the patients either do not respond sufficiently to infliximab therapy or loose efficacy over time. The large individual variation in the serum drug concentrations on standard doses and the development of anti-drug antibodies are thought to be main reasons for these treatment failures. An individualised treatment strategy based on systematic assessments of serum drug concentrations, therapeutic drug monitoring, has been proposed as a clinical tool to optimise efficacy of infliximab treatment. Therapeutic drug monitoring seems reasonable both from a clinical and an economical point of view, but the effectiveness of this treatment strategy still remain to be shown. The NOR-DRUM study is planned as a national, randomised controlled multicentre trial in two parts aiming to assess the effectiveness of therapeutic drug monitoring in order to achieve remission in patients with immunological inflammatory diseases starting infliximab treatment (part A) and in order to maintain disease control in patients on maintenance infliximab treatment (part B). The results of the NOR-DRUM study will hopefully contribute to an implementation of a personalised medicine approach to treatment with infliximab and other biological drugs.

Conditions

Rheumatoid Arthritis; Spondyloarthritis; Ankylosing Spondylitis; Crohn Disease; Ulcerative Colitis; Psoriasis; Psoriatic Arthritis

Keywords

infliximab; therapeutic drug monitoring; anti drug antibodies; TDM

Outcome Measures

Primary Outcomes (2)

• Proportion of patients in remission defined by disease specific composite scores Study part A

  Definition of remission: DAS 28 score \<2.6 in patients with RA and PsA, ASDAS score \<1.3 in patients with SpA, Mayo score of ≤2 with no sub scores \>1 in patients with UC, HBI score of ≤4 in CD and PASI score of ≤4 in patients with Ps.

  30 weeks

• Sustained disease control throughout the study period without disease worsening defined by disease specific composite scores Study part B

  Definition of disease worsening: RA/PsA: Change DAS28 of ≥ 1.2 and min DAS 3.2 SpA: Increase in ASDAS of ≥1.1 and min ASDAS of 2.1 UC: Increase in Partial Mayo score of ≥ 3 and min score of ≥ 5 CD: Increase in HBI of ≥ 4 points and min score of 7 Ps: Increase in PASI of ≥ 3 points and min PASI score of 5 Or: Patient and investigator consensus on disease worsening

  52 weeks

Secondary Outcomes (35)

• Time to sustained remission (Part A)

  Assessed at all time points up to 30 weeks

• Patient's and physician's global assessment of disease activity (Part A and B)

  30 weeks (A) and 52 weeks (B)

• ESR (Part A and B)

  30 weeks (A) and 52 weeks (B)

• CRP (Part A and B)

  30 weeks (A) and 52 weeks (B)

• Occurrence of anti-drug antibodies (Part A and B)

  30 weeks (A) and 52 weeks (B)

Study Arms (2)

Therapeutic drug monitoring

EXPERIMENTAL

Administration of infliximab according to a treatment strategy based on therapeutic drug monitoring and assessments of anti-drug antibodies

Other: Therapeutic drug monitoring

Standard care

ACTIVE COMPARATOR

Administration of infliximab according to standard clinical care, without knowledge of drug levels or status of anti-drug antibodies

Other: Standard care

Interventions

Therapeutic drug monitoring OTHER

Treatment algorithm based on assessments of serum drug levels and anti-drug antibodies

Therapeutic drug monitoring

Standard care OTHER

Treatment algorithm based on standard clinical assessments, without knowledge of serum drug levels and anti-drug antibodies

Standard care

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• NOR-DRUM A
• A clinical diagnosis of one of the following; rheumatoid arthritis, spondyloarthritis (including ankylosing spondylitis), psoriatic arthritis\*, ulcerative colitis, Crohn's disease or chronic plaque psoriasis
• Male or non-pregnant female
• ≥18 and \< 75 years of age at screening
• A clinical indication to start INX
• Subject not in remission according to diagnosis-specific disease activity scores
• Subject capable of understanding and signing an informed consent form
• Patients with psoriatic arthritis with predominantly axial manifestations should be included and assessed as spondyloarthritis
• NOR-DRUM B
• A clinical diagnosis of one of the following; rheumatoid arthritis, spondyloarthritis (including ankylosing spondylitis), psoriatic arthritis\*, ulcerative colitis, Crohn's disease or chronic plaque psoriasis
• Male or non-pregnant female
• ≥18 and \< 75 years of age at screening
• On maintenance therapy with infliximab for a minimum of 30 weeks and a maximum of 3 years
• A clinical indication for further infliximab treatment
• Subject capable of understanding and signing an informed consent form

You may not qualify if:

• NOR-DRUM A
• Major co-morbidities, such as previous malignancies within the last 5 years, severe diabetes mellitus, severe infections (including HIV), uncontrollable hypertension, severe cardiovascular disease (NYHA class 3 or 4), severe respiratory diseases, demyelinating disease, significant chronic widespread pain syndrome, laboratory abnormalities or significant renal or hepatic disease and/or other diseases or conditions where treatment with infliximab is either found contra-indicated by the clinician or which make adherence to the protocol difficult
• A positive screening for TB and hepatitis
• Inadequate birth control, pregnancy or subject considering becoming pregnant during the study period
• Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol difficult
• Prior use of infliximab within the last 6 months
• NOR-DRUM B
• Major co-morbidities, such as previous malignancies within the last 5 years, severe diabetes mellitus, severe infections, uncontrollable hypertension, severe cardiovascular disease (NYHA class 3 or 4), severe respiratory diseases, demyelinating disease, significant chronic widespread pain syndrome, laboratory abnormalities or significant renal or hepatic disease and/or other diseases or conditions where treatment with infliximab is either found contra-indicated by the clinician or which make adherence to the protocol difficult
• Inadequate birth control, pregnancy or subject considering becoming pregnant during the study period
• Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol difficult

Sponsors & Collaborators

• Diakonhjemmet Hospital: lead
• Oslo University Hospital: collaborator
• University Hospital, Akershus: collaborator

Study Sites (21)

Akershus University Hospital

Oslo, Lørenskog, 1478, Norway

Location

Sørlandet Sykehus, Arendal

Arendal, Norway

Location

Ålesund, HELSE MØRE OG ROMSDAL HF

Ålesund, Norway

Location

Haukeland, HELSE BERGEN HF,

Bergen, Norway

Location

Bodø, NORDLANDSSYKEHUSET

Bodø, Norway

Location

Drammen, VESTRE VIKEN HF

Drammen, Norway

Location

Elverum, SYKEHUSET INNLANDET HF

Elverum, Norway

Location

Helse Førde Hf

Førde, Norway

Location

Hamar, SYKEHUSET INNLANDET HF

Hamar, Norway

Location

HAUGESUND SANITETSFORENING revmatismesykehus

Haugesund, Norway

Location

Haugesund Sjukehus

Haugesund, Norway

Location

SØRLANDET SYKEHUS HF Kristiansand

Kristiansand, Norway

Location

REVMATISMESYKEHUSET AS, Lillehammer

Lillehammer, Norway

Location

Sykehuset Østfold Moss

Moss, 1535, Norway

Location

Rikshospitalet

Oslo, 0372, Norway

Location

Diakonhjemmet Sykehus

Oslo, 0687, Norway

Location

Betanien Hospital

Skien, Norway

Location

Stavanger Universitetssjukehus

Stavanger, Norway

Location

Tromsø, UNIVERSITETSSYKEHUSET NORD-NORGE HF

Tromsø, Norway

Location

St Olavs Hospital

Trondheim, Norway

Location

Sykehuset Vestfold, Tønsberg

Tønsberg, Norway

Location

Related Publications (3)

• Syversen SW, Jorgensen KK, Goll GL, Brun MK, Sandanger O, Bjorlykke KH, Sexton J, Olsen IC, Gehin JE, Warren DJ, Klaasen RA, Noraberg G, Bruun TJ, Dotterud CK, Ljosa MKA, Haugen AJ, Njalla RJ, Zettel C, Ystrom CM, Bragnes YH, Skorpe S, Thune T, Seeberg KA, Michelsen B, Blomgren IM, Strand EK, Mielnik P, Torp R, Mork C, Kvien TK, Jahnsen J, Bolstad N, Haavardsholm EA. Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial. JAMA. 2021 Dec 21;326(23):2375-2384. doi: 10.1001/jama.2021.21316.

  PMID: 34932077 DERIVED

• Syversen SW, Goll GL, Jorgensen KK, Sandanger O, Sexton J, Olsen IC, Gehin JE, Warren DJ, Brun MK, Klaasen RA, Karlsen LN, Noraberg G, Zettel C, Ljosa MKA, Haugen AJ, Njalla RJ, Bruun TJ, Seeberg KA, Michelsen B, Strand EK, Skorpe S, Blomgren IM, Bragnes YH, Dotterud CK, Thune T, Ystrom CM, Torp R, Mielnik P, Mork C, Kvien TK, Jahnsen J, Bolstad N, Haavardsholm EA. Effect of Therapeutic Drug Monitoring vs Standard Therapy During Infliximab Induction on Disease Remission in Patients With Chronic Immune-Mediated Inflammatory Diseases: A Randomized Clinical Trial. JAMA. 2021 May 4;325(17):1744-1754. doi: 10.1001/jama.2021.4172.

  PMID: 33944876 DERIVED

• Syversen SW, Goll GL, Jorgensen KK, Olsen IC, Sandanger O, Gehin JE, Warren DJ, Sexton J, Mork C, Jahnsen J, Kvien TK, Bolstad N, Haavardsholm EA. Therapeutic drug monitoring of infliximab compared to standard clinical treatment with infliximab: study protocol for a randomised, controlled, open, parallel-group, phase IV study (the NOR-DRUM study). Trials. 2020 Jan 6;21(1):13. doi: 10.1186/s13063-019-3734-4.

  PMID: 31907007 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid; Spondylarthritis; Spondylitis, Ankylosing; Crohn Disease; Colitis, Ulcerative; Psoriasis; Arthritis, Psoriatic

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Spondylitis; Spinal Diseases; Bone Diseases; Axial Spondyloarthritis; Spondylarthropathies; Ankylosis; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases; Skin Diseases, Papulosquamous; Skin Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Espen A Haavardsholm, MD, PhD

  Diakonhjemmet Hospital

  PRINCIPAL INVESTIGATOR

• Tore K Kvien, MD, PhD

  Diakonhjemmet Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: March 9, 2017
• Study Start: March 1, 2017
• Primary Completion: December 14, 2020
• Study Completion: December 14, 2020
• Last Updated: March 8, 2021

Record last verified: 2021-03

Locations

NO (21)