A Randomized Controlled Pilot Trial of Cyclosporine Vs Steroids in DRESS
试验速览
- 阶段
- 早期 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Percentage of patients with complete or near complete resolution of organ involvement at day 30, on steroid therapy and cyclosporine therapy
研究概览
简要总结
Current treatments for patients with drug reaction with eosinophilia and systemic symptoms (DRESS) include supportive care, steroids and cyclosporine. No randomized controlled trial (RCT) exists in comparing these treatments and all available literature comes in the form of case reports and case series. These two treatments are considered standard of care and this trial seeks only to compare outcomes of DRESS between these two therapies. No additional labs, therapies or procedures will be used apart from those that are routinely done for patients with this diagnosis.
This will be a pilot study to determine efficacy of the two therapies with particular endpoints in mind so that the investigators can study the safety of these two therapies in patients with DRESS.
Data suggests a potential benefit for adults with DRESS using either steroids or cyclosporine but the investigators are seeking a comparison of efficacy of these two therapies. The study population will include adults with a Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) score of greater than 4 (i.e. a likely diagnosis of DRESS). The investigators will exclude patients with sepsis, active Hepatitis B or C, active tuberculosis, a documented allergy to steroids or cyclosporine, and patients with an estimated glomerular filtration rate (eGFR) < 30 (unless on dialysis in which case the participants will be included).
详细描述
Current treatments for patients with drug reaction with eosinophilia and systemic symptoms (DRESS) include supportive care, steroids, cyclosporine and to a lesser extent, intravenous immunoglobulin (IVIG). Regarding IVIG, a recent case series suggests no improved benefit in adults. No randomized controlled trial (RCT) exists in comparing these treatments and all available literature comes in the form of case reports and case series. These two treatments are considered standard of care and this trial seeks only to compare outcomes of DRESS between these two therapies. No additional labs, therapies or procedures will be used apart from those that are routinely done for patients with this diagnosis.
This will be a pilot study to determine efficacy of the two therapies with particular endpoints in mind so that the investigators can study the safety of these two therapies in patients with DRESS. Hopefully, this study will allow the investigators to better power a full prospective trial in the future.
This is a potentially life-threatening severe cutaneous adverse reaction (SCAR) with significant potential morbidity. Data suggests a potential benefit for adults with DRESS using either steroids or cyclosporine but the investigators are seeking a comparison of efficacy of these two therapies. The study population will include adults with a Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) score of greater than 4 (i.e. a likely diagnosis of DRESS). The investigators will exclude patients with sepsis, active Hepatitis B or C, active tuberculosis, a documented allergy to steroids or cyclosporine, and patients with an estimated glomerular filtration rate (eGFR) < 30 (unless on dialysis in which case the participants will be included).
Participants will be randomized using a randomization protocol at all sites. Primary endpoints will include percentage of participants with complete or near complete resolution of organ involvement as well as erythema resolution at day 7 and day 30.
Secondary endpoints will be:
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
- •Adults with a RegiSCAR score of greater than 4 (i.e a likely diagnosis of DRESS)
排除标准
- •Active sepsis
- •Active hepatitis B or C
- •Active tuberculosis
- •Documented allergy to steroids or cyclosporine
- •Estimated glomerular filtration rate (eGFR) < 30 (unless on dialysis, in which case they will be included)
研究组 & 干预措施
Cyclosporine
All Patients start with 5 mg/kg/day (3 mg/kg/day if renal impairment) PO divided bid for 7 days (or IV if patient is NPO)
- If complete resolution, stop cyclosporine and monitor closely for relapse
a. If patient relapses, give 5 (3 if renal impairment) mg/kg/day PO divided bid PO for 7 days
i. If down-trending, start oral taper regimen
ii. If not down-trending, switch to steroid arm 2. If >25% improvement and labs are down-trending, start the oral taper regimen. 3. If 0-25% improvement, give 5 (3 if renal impairment) mg/kg/day PO divided bid for 3 days
- If down-trending, start oral taper regimen
- If not down-trending, switch to steroid arm
- If no improvement or up-trending labs at 7 days, switch to steroid arm
Oral Taper Regimen set as 3 mg/kg PO divided bid for 14 days, then 2 mg/kg PO divided bid for 20 days. If renal impairment, oral taper regimen set as 2 mg/kg PO divided bid for 14 days, then 1 mg/kg PO divided bid for 20 days
干预措施: Cyclosporine (Drug)
Corticosteroids
All Patients start with 500 mg IV Methylprednisolone for 3 days
-
If >25% improvement (must be >25% in all involved organs), start the taper regimen 2. If 0-25% improvement (in ≥1 involved internal organ), give 500 mg IV Methylprednisolone for 4 days
-
If no improvement, switch to cyclosporine arm of treatment
-
If 0-25% improvement, give 500 mg IV Methylprednisolone for 3 days
i. If labs are down-trending, start the taper regimen
ii. If labs are not down-trending, switch to cyclosporine arm of the study
c. If >25% improvement, start the taper regimen
Taper Regimen set as:
- 125 mg IV Methylprednisolone x3 days
- 1.2 mg/kg PO prednisone x1 week
- 1 mg/kg PO prednisone x1 week
- 0.8 mg/kg PO prednisone x1 week
- 0.6 mg/kg PO prednisone x1 week
- 0.4 mg/kg PO prednisone x1 week
- 0.2 mg/kg PO prednisone x1 week
- 0.1 mg/kg PO prednisone x1 week
- 0.05 mg/kg PO prednisone x1 week
干预措施: Methylprednisolone and Prednisone (Drug)
结局指标
主要结局
Percentage of patients with complete or near complete resolution of organ involvement at day 30, on steroid therapy and cyclosporine therapy
时间窗: Day 30
Measured by the following quantitative metrics: * Creatinine within 1.25x of baseline or upper limit of normal, whichever is higher * Aspartate Aminotransferase (AST) within 1.5x of baseline or upper limit of normal, whichever is higher * Troponin-T, Creatine Kinase Myocardial Band (CK-MB), Pro B-type Natriuretic Peptide (Pro-BNP), and lipase within 1.25x of baseline or upper limit of normal, whichever is higher * Resolution of interstitial pneumonitis on chest x-ray
Percentage of patients with complete or near complete resolution of erythema at day 7, on steroid therapy and cyclosporine therapy
时间窗: Day 7
Clinical measurement of erythema
Percentage of patients with complete or near complete resolution of erythema at day 30, on steroid therapy and cyclosporine therapy
时间窗: Day 30
Clinical measurement of erythema
次要结局
- 30-day readmission rate(Day 30)
- Percentage of patients with resolution of facial edema(Day 30)
- Percentage of patients with resolution of lymphadenopathy(Day 30)
- Patients with autoimmune disease development(Day 90)
- Total days of hospitalization after initial dermatology consult(0-120 days)
- Percentage of patients with resolution of fever(Day 30)
- Percentage of patients with resolution of pruritus(Day 30)
- Absolute eosinophil proportion compared to peak value(Day 30)
- Viral reactivation(Day 90)
- Mortality(Day 90)
研究者
Scott Worswick
Associate Professor
University of Southern California