The Norwegian Drug Monitoring Study

NCT ID: NCT03074656

Last Updated: 2021-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 611 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-01
• Study Completion Date: 2020-12-14

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Therapeutic drug monitoring

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

Group Type: EXPERIMENTAL

Therapeutic drug monitoring

Intervention Type: OTHER

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

Standard care

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

Group Type: ACTIVE_COMPARATOR

Standard care

Intervention Type: OTHER

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

Interventions

Therapeutic drug monitoring

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

Intervention Type: OTHER

Standard care

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

NOR-DRUM A

1. 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

2. Male or non-pregnant female

3. ≥18 and < 75 years of age at screening

4. A clinical indication to start INX

5. Subject not in remission according to diagnosis-specific disease activity scores

6. 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

1. 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

2. Male or non-pregnant female

3. ≥18 and < 75 years of age at screening

4. On maintenance therapy with infliximab for a minimum of 30 weeks and a maximum of 3 years

5. A clinical indication for further infliximab treatment

6. Subject capable of understanding and signing an informed consent form

• Patients with psoriatic arthritis and predominantly axial manifestations should be included and assessed as spondyloarthritis

Exclusion Criteria

NOR-DRUM A

1. 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

2. A positive screening for TB and hepatitis

3. Inadequate birth control, pregnancy or subject considering becoming pregnant during the study period

4. Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol difficult

5. Prior use of infliximab within the last 6 months

NOR-DRUM B

1. 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

2. Inadequate birth control, pregnancy or subject considering becoming pregnant during the study period

3. Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol difficult

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oslo University Hospital

OTHER

Sponsor Role: collaborator

University Hospital, Akershus

OTHER

Sponsor Role: collaborator

Diakonhjemmet Hospital

OTHER

Sponsor Role: lead

Responsible Party

Espen A. Haavardsholm, MD PhD

Professor, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Espen A Haavardsholm, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Diakonhjemmet Hospital

Tore K Kvien, MD, PhD

Role: STUDY_DIRECTOR

Diakonhjemmet Hospital

Locations

Akershus University Hospital

Oslo, Lørenskog, Norway

Sørlandet Sykehus, Arendal

Arendal, , Norway

Ålesund, HELSE MØRE OG ROMSDAL HF

Ålesund, , Norway

Haukeland, HELSE BERGEN HF,

Bergen, , Norway

Bodø, NORDLANDSSYKEHUSET

Bodø, , Norway

Drammen, VESTRE VIKEN HF

Drammen, , Norway

Elverum, SYKEHUSET INNLANDET HF

Elverum, , Norway

Helse Førde Hf

Førde, , Norway

Hamar, SYKEHUSET INNLANDET HF

Hamar, , Norway

HAUGESUND SANITETSFORENING revmatismesykehus

Haugesund, , Norway

Haugesund Sjukehus

Haugesund, , Norway

SØRLANDET SYKEHUS HF Kristiansand

Kristiansand, , Norway

REVMATISMESYKEHUSET AS, Lillehammer

Lillehammer, , Norway

Sykehuset Østfold Moss

Moss, , Norway

Rikshospitalet

Oslo, , Norway

Diakonhjemmet Sykehus

Oslo, , Norway

Betanien Hospital

Skien, , Norway

Stavanger Universitetssjukehus

Stavanger, , Norway

Tromsø, UNIVERSITETSSYKEHUSET NORD-NORGE HF

Tromsø, , Norway

St Olavs Hospital

Trondheim, , Norway

Sykehuset Vestfold, Tønsberg

Tønsberg, , Norway

Countries

Norway

References

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.

Reference Type: DERIVED

PMID: 34932077 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33944876 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31907007 (View on PubMed)

Other Identifiers

DIA2016-1

Identifier Type: -

Identifier Source: org_study_id