A NORwegian Multicentre Randomised Controlled Trial Assessing the Effectiveness of Tailoring Infliximab Treatment by Therapeutic DRUg Monitoring - The NOR-DRUM Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 611
- 试验地点
- 25
- 主要终点
- Proportion of patients in remission defined by disease specific composite scores Study part A
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
- •Patients with psoriatic arthritis and predominantly axial manifestations should be included and assessed as spondyloarthritis
排除标准
- •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
- •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
结局指标
主要结局
Proportion of patients in remission defined by disease specific composite scores Study part A
时间窗: 30 weeks
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.
Sustained disease control throughout the study period without disease worsening defined by disease specific composite scores Study part B
时间窗: 52 weeks
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
次要结局
- 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))
- Occurrence of drug discontinuation (Part A and B)(30 weeks (A) and 52 weeks (B))
- Proportion of patients with improvement defined by disease specific composite scores (Part A)(14 weeks)
- Time to remission (Part A)(Assessed at all time points up to week 30)
- DAS28 (RA and PsA only)(30 weeks (A) and 52 weeks (B))
- Partial Mayo score(30 weeks (A) and 52 weeks (B))
- SDAI (RA and PsA only)(30 weeks (A) and 52 weeks (B))
- EULAR response (RA and PsA only)(30 weeks (A))
- ACR/EULAR remission(30 weeks (A))
- Cost effectiveness, QALY(30 weeks (A) and 52 weeks (B))
- Cost effectiveness, ICERs(30 weeks (A) and 52 weeks (B))
- Health utility (EQ-5D)(30 weeks (A) and 52 weeks (B))
- Quality of life (SF-36)(30 weeks (A) and 52 weeks (B))
- Safety (adverse events frequency)(30 weeks (A) and 52 weeks (B))
- Time to disease worsening(52 weeks)
- Proportion of patients in remission, diagnostic subgroups (overall in B)(30 weeks (A) and 52 weeks (B))
- Serum drug level(Assessed at all time points up to 30 weeks)
- ACR response(30 weeks (A))
- DAPSA (PsA only)(30 weeks (A) and 52 weeks (B))
- BASDAI (SpA only)(30 weeks (A) and 52 weeks (B))
- ASDAS(30 weeks (A) and 52 weeks (B))
- Partial Mayo Score (UC only)(30 weeks (A) and 52 weeks (B))
- Harvey-Bradshaw Index (CD only)(30 weeks (A) and 52 weeks (B))
- Psoriasis Area and Severity Index (PASI) (Ps only)(30 weeks (A) and 52 weeks (B))
- Modified Health Assessment Questionnaire(30 weeks (A) and 52 weeks (B))
- Rheumatoid Arthritis Impact of Disease (RA only)(30 weeks (A) and 52 weeks (B))
- Psoriatic Arthritis Impact of Disease (PsAID) score(30 weeks (A) and 52 weeks (B))
- Total drug consumption(30 weeks (A) and 52 weeks (B))
- Dermatology Life Quality Index (DLQI)(30 weeks (A) and 52 weeks (B))
- Calprotectin(30 weeks (A) and 52 weeks (B))
- Inflammatory Bowel Disease Questionnaire (IBDQ)(30 weeks (A) and 52 weeks (B))
研究者
Espen A. Haavardsholm, MD PhD
Professor, MD, PhD
Diakonhjemmet Hospital