Cardiac Sarcoidosis Multi-Center Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 44
- 主要终点
- Summed perfusion rest score (SPRS) on FDG-PET scan
研究概览
简要总结
Prospective randomized controlled trial comparing low dose Prednisone(or Prednisolone)/Methotrexate combination to standard dose Prednisone(or Prednisolone) in patients diagnosed with acute active clinically manifest cardiac sarcoidosis and not yet treated.
The Investigators hypothesize that low dose Prednisone(or Prednisolone)/Methotrexate combination will be as effective as standard dose Prednisone(or Prednisolone), and result in significantly better quality of life and less toxicity than standard dose Prednisone(or Prednisolone).
详细描述
Subjects meeting the study inclusion/exclusion criteria will be randomized equally to receive either:
Everywhere but Japan:
- Prednisone 0.5 mg kg/day for 6-months (MAX dose 30 mg per day) or
- Methotrexate 15-20 mg po, sc, or IM once a week for 6-months + Folic Acid OD (exact dose and directions at physician) for 6 months + Prednisone 20 mg day for 1 month, then 10 mg OD for 1 month, then 5 mg OD for one month then STOP
In Japan:
- Prednisone or prednisolone 0.5 mg/kg po (max 30mg) for one month then reduce by 5 mg per month for five months or
- Methotrexate 5-20mg po, sc or IM once week for 6-months +Folic Acid 2-5 mg OD for 6-months+Prednisone or prednisolone 20mg OD for 1 month then 10mg OD for 1 month then 5 mg OD one month
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(i) Cardiac sarcoidosis presenting with one or more of the following clinical findings:
- •advanced conduction system disease (defined as Mobitz II AV block or third degree AV block)
- •significant sinus node dysfunction (defined as average HR less than 40bpm when awake and/or sustained atrial arrhythmias)
- •non- sustained or sustained ventricular arrhythmia
- •left ventricular dysfunction (LVEF < 50%)
- •right ventricular dysfunction (RVEF < 40%)
- •(ii) No alternative explanation for clinical features
- •(iii) Nuclear Imaging within six-months of enrollment consisting of FDG-PET scan with FDG uptake suggestive of active CS and myocardial perfusion imaging
- •AND ONE OR BOTH OF FOLLOWING
- •(iv) Positive biopsy for Sarcoid (either EMB or extra-cardiac)
- •(v) CT Chest showing features consistent with pulmonary sarcoidosis and/or mediastinal and/or hilar lymphadenopathy
排除标准
- •Current or recent (within two months) non-topical treatment for sarcoidosis
- •Current Oral/IV treatment of duration greater than 5 days
- •Currently taking Methotrexate or Prednisone for another health condition
- •Intolerance or contra-indication to Methotrexate or Prednisone
- •Patient does not meet all of the above listed inclusion criteria
- •Patient is unable or unwilling to provide informed consent
- •Patient is included in another randomized clinical trial
- •Patient has a contraindication to PET imaging or is unlikely to tolerate due to severe claustrophobia
- •Pregnancy (all women of child bearing age and potential will have a negative BHCG test before enrollment)
- •Breastfeeding
- •Women of childbearing age who refuse to use a highly effective and medically acceptable form of contraception throughout the study
- •Patients for whom the investigator believes that the trial is not in the interest of the patient
研究组 & 干预措施
Methotrexate
[Dose everywhere except Japan] Methotrexate 15-20 mg orally, sc, or IM once a week for 6 months + Prednisone 20 mg po daily for one month then 10 mg po daily for one month then 5 mg po daily for one month and then stop. Also Folic Acid OD (exact dose and directions at physicians discretion) for 6 months.
[Dose in Japan] Methotrexate 5-20mg mg orally, sc, or IM once a week for 6 months+ Prednisone or Prednisolone 20mg OD for 1 month then 10mg OD for 1 month then 5 mg OD one month. Also Folic Acid 2 mg po daily for 6 months.
干预措施: Prednisone or Prednisolone (Drug)
Prednisone (or Prednisolone)
[Dose everywhere except Japan] Prednisone 0.5 mg kg/day for 6 months (max dose 30 mg)
[Dose in Japan] Prednisone or prednisolone 0.5 mg/kg po (max 30mg) for one month then reduce by 5 mg per month for five months
干预措施: Prednisone or Prednisolone (Drug)
Methotrexate
[Dose everywhere except Japan] Methotrexate 15-20 mg orally, sc, or IM once a week for 6 months + Prednisone 20 mg po daily for one month then 10 mg po daily for one month then 5 mg po daily for one month and then stop. Also Folic Acid OD (exact dose and directions at physicians discretion) for 6 months.
[Dose in Japan] Methotrexate 5-20mg mg orally, sc, or IM once a week for 6 months+ Prednisone or Prednisolone 20mg OD for 1 month then 10mg OD for 1 month then 5 mg OD one month. Also Folic Acid 2 mg po daily for 6 months.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Summed perfusion rest score (SPRS) on FDG-PET scan
时间窗: 6 months
Measure of myocardial scarring and fibrosis (blinded core lab analysis)
次要结局
- LVEF and RVEF assessed on echocardiogram(6 months)
- Highly sensitive Troponin I levels and BNP levels(6 months)
- Patient reported symptoms related to medication(6 months)
- Disease Specific Quality of Life (KSQ and SAT)(6 months)
- BMI(6 months)
- Generic Quality of Life (SF 36)(6 months)
- Mortality(6 months)
- Complete heart block(6 months)
- Medication related adverse events(6 months)
- Medication compliance(6 months)
- Blood pressure(6 months)
- HbA1C(6 months)
- Ventricular arrhythmia burden(6 months)
- Cardiovascular hospitalizations(6 months)
- Modified Cleveland Clinic Glucocorticoid Toxicity Score(6 months)
- Glucocorticoid Toxicity Index(6 months)
- T-score on bone density scan(6 months)
- FDG-PET and myocardial perfusion(6 month scan)
- CMR Endpoints(6 months)