Treatments Against RA and Effect on FDG-PET/CT (The TARGET Trial)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 159
- 试验地点
- 31
- 主要终点
- Change From Baseline in Vascular Inflammation as Measured by FDG-PET/CT at 6 Months
研究概览
简要总结
In a randomized controlled clinical trial, investigators will compare the effects on [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) from two treatment regimens in rheumatoid arthritis (RA) patients deemed methotrexate inadequate responders (MTX-IRs). Two common RA treatments will be compared: triple therapy (sulfasalazine, methotrexate, and hydroxychloroquine) versus tumor necrosis factor (TNF) inhibitor (etanercept or adalimumab, plus background methotrexate for all subjects and hydroxychloroquine for subjects who were taking this at screening).
详细描述
Consenting subjects will be screened for eligibility and randomized to a treatment arm. Subjects will be randomized to a treatment arm with either synthetic disease-modifying antirheumatic drugs (DMARDs) [triple therapy: sulfasalazine, methotrexate, and hydroxychloroquine] or biologic DMARDs [etanercept or adalimumab, plus background methotrexate for all subjects and hydroxychloroquine for subjects who were taking this at screening].
Once randomized, a baseline visit will be conducted with each subject. Baseline data collection includes questionnaires, disease activity score, and the first FDG-PET/CT imaging. After the baseline at week 0, subjects will visit with their rheumatologist at weeks 6, 12, 18, and 24 for safety labs and further collection of disease activity scores and questionnaires. The second FDG-PET/CT will be performed at week 24. Blood specimens will be collected at weeks 0, 6, 18, and 24 for bioassays. Subject participation will end after the week 24 visit.
Patients and care providers will be unblinded. The FDG-PET/CT image readers will be blinded to treatment arm as well as timepoint of image acquisition.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fulfill American College of Rheumatology/European League Against Rheumatism 2010 criteria for RA
- •Men ≥ 45 years and women ≥ 50 years
- •MTX monotherapy for ≥ 8 weeks at ≥ 15mg weekly or ≥ 7.5 mg weekly with a documented intolerance to higher doses
- •No non-biologic DMARDs in preceding two months (other than MTX and HCQ)
- •Disease Activity Score-28 > 3.2
- •Able to sign informed consent
排除标准
- •Use of biologic DMARD within the past 6 months or use of rituximab ever
- •Current use of >10mg per day of prednisone
- •Use of a high-intensity statin lipid lowering drug or PCSK9 inhibitor in the past 12 months
- •Prior patient reported, physician diagnosed clinical cardiovascular (CV) event
- •Insulin-dependent or uncontrolled diabetes mellitus (DM)
- •Systemic lupus erythematosus (SLE) or other autoimmune and chronic inflammatory diseases (i.e. inflammatory bowel disease, sarcoidosis)
- •Cancer treated in the last 5 years (except basal and squamous cell) or any lymphoma or melanoma
- •Known pregnancy, HIV, Hepatitis B Virus, Hepatitis C Virus, active (or untreated latent) tuberculosis
- •Baseline: liver, renal or blood count abnormalities, Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- •Known sulfa allergy, macular disease or hypersensitivity to treatments; known demyelinating disease; uncompensated Congestive Heart Failure (CHF)
- •Intra-articular injection within the 4 weeks prior to baseline FDG PET/CT
- •2 or more high dose radiation scans in the past year (CT scan with contrast, angiogram, SPECT nuclear medicine scan, myocardial/cardiac perfusion scan)
研究组 & 干预措施
Triple therapy (MTX+SSZ+HCQ)
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate [MTX]).
干预措施: Methotrexate (Drug)
Triple therapy (MTX+SSZ+HCQ)
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate [MTX]).
干预措施: Sulfasalazine (Drug)
Triple therapy (MTX+SSZ+HCQ)
Sulfasalazine (SSZ) 1 g bid and hydroxychloroquine (HCQ) 200 mg twice daily, not to exceed 6.5mg/kg HCQ (in addition to concomitant methotrexate [MTX]).
干预措施: Hydroxychloroquine (Drug)
TNF inhibitor (etanercept or adalimumab)
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
干预措施: Methotrexate (Drug)
TNF inhibitor (etanercept or adalimumab)
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
干预措施: Etanercept (Drug)
TNF inhibitor (etanercept or adalimumab)
etanercept 50 mg subcutaneously weekly or adalimumab 40 mg subcutaneously every other week (in addition to concomitant methotrexate, plus hydroxychloroquine, for subjects who were taking this at screening). Biologic treatment will be assigned randomly.
干预措施: Adalimumab (Drug)
结局指标
主要结局
Change From Baseline in Vascular Inflammation as Measured by FDG-PET/CT at 6 Months
时间窗: 0, 6 months
The primary outcome was the change in the mean of the maximum of the target to background ratio (TBR) in the most diseased segment (MDS) of of the index vessel as measured by FDG-PET/CT scans conducted at baseline and after 24 weeks of randomized treatment allocation (MDS meanmaxTBR). The index vessel is the vessel (either aorta, left carotid, or right carotid) with the highest meanmaxTBR at baseline. Higher values indicate greater vascular inflammation. FDG uptake measurement: PET-CT images were batch-analyzed by an investigator blinded to the patients' clinical information. FDG uptake was evaluated within the wall of the ascending aorta and bilateral carotid arteries (as maximum and mean standardized FDG uptake value \[SUVmax and SUVmean, respectively\]) approximately every 5 mm on axial images. Subsequently, the target-to-background ratio (TBR) was reported (ratio of the average arterial to blood axial slice SUVmax) to correct for the blood compartment contribution.
次要结局
- Change From Baseline in the Average TBR of the Aorta(0, 6 months)
- Change From Baseline in the Average TBR of the Bilateral Carotids(0, 6 months)
- Change From Baseline in the Average TBR of the Index Vessel(0, 6 months)
- Change From Baseline in the MDS of the Aorta(0, 6 months)
研究者
Daniel H. Solomon, M.D.,MPH
Chief, Section of Clinical Sciences
Brigham and Women's Hospital