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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).
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cyclosporine | Active Comparator | 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)
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 |
|
| Corticosteroids | Experimental | All Patients start with 500 mg IV Methylprednisolone for 3 days 1. 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
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:
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclosporine | Drug | Patients randomized to cyclosporine will be treated as mentioned under "Arm/Group Description" |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of patients with complete or near complete resolution of organ involvement at day 30, on steroid therapy and cyclosporine therapy | Measured by the following quantitative metrics:
| Day 7 |
| Percentage of patients with complete or near complete resolution of organ involvement at day 30, on steroid therapy and cyclosporine therapy | Measured by the following quantitative metrics:
| Day 30 |
| Percentage of patients with complete or near complete resolution of erythema at day 7, on steroid therapy and cyclosporine therapy | Clinical measurement of erythema | Day 7 |
| Percentage of patients with complete or near complete resolution of erythema at day 30, on steroid therapy and cyclosporine therapy | Clinical measurement of erythema | Day 30 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of patients with resolution of fever | Less than 38 degrees Celsius for at least 24 hours | Day 7 |
| Percentage of patients with resolution of fever | Less than 38 degrees Celsius for at least 24 hours |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| USC | Los Angeles | California | 90033 | United States |
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| ID | Term |
|---|---|
| D063926 | Drug Hypersensitivity Syndrome |
| ID | Term |
|---|---|
| D003875 | Drug Eruptions |
| D003872 | Dermatitis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D016572 | Cyclosporine |
| D008775 | Methylprednisolone |
| D011241 | Prednisone |
| ID | Term |
|---|---|
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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| Methylprednisolone and Prednisone | Drug | All patients randomized to steroids will initially be treated with IV methylprednisolone and eventually started on an oral prednisone taper. |
|
| Day 30 |
| Percentage of patients with resolution of facial edema | Clinical resolution of edema for at least 24 hours | Day 7 |
| Percentage of patients with resolution of facial edema | Clinical resolution of edema for at least 24 hours | Day 30 |
| Percentage of patients with resolution of pruritus | Resolution for at least 24 hours | Day 7 |
| Percentage of patients with resolution of pruritus | Resolution for at least 24 hours | Day 30 |
| Percentage of patients with resolution of lymphadenopathy | Clinical resolution of lymphadenopathy for at least 24 hours | Day 7 |
| Percentage of patients with resolution of lymphadenopathy | Clinical resolution of lymphadenopathy for at least 24 hours | Day 30 |
| Absolute eosinophil proportion compared to peak value | Proportion of absolute eosinophils | Day 7 |
| Absolute eosinophil proportion compared to peak value | Proportion of absolute eosinophils | Day 30 |
| Patients with autoimmune disease development | Measured by titers of autoimmune markers (Antinuclear Antibody (ANA), Thyroid Stimulating Hormone (TSH)) compared to baseline | Day 30 |
| Patients with autoimmune disease development | Measured by titers of autoimmune markers (Antinuclear Antibody (ANA), Thyroid Stimulating Hormone (TSH)) compared to baseline | Day 90 |
| Total days of hospitalization after initial dermatology consult | Number of days | 0-120 days |
| Viral reactivation | Measured by titers of Human Herpesvirus 6 (HHV6), Cytomegalovirus (CMV), and Epstein-Barr Virus (EBV) | Day 30 |
| Viral reactivation | Measured by titers of Human Herpesvirus 6 (HHV6), Cytomegalovirus (CMV), and Epstein-Barr Virus (EBV) | Day 60 |
| Viral reactivation | Measured by titers of Human Herpesvirus 6 (HHV6), Cytomegalovirus (CMV), and Epstein-Barr Virus (EBV) | Day 90 |
| Mortality | Proportion of patient mortality | Day 7 |
| Mortality | Proportion of patient mortality | Day 30 |
| Mortality | Proportion of patient mortality | Day 90 |
| 30-day readmission rate | Proportion of patients re-admitted to the hospital within 30 days of discharge | Day 30 |
| D006968 |
| Hypersensitivity, Delayed |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D004342 | Drug Hypersensitivity |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D010455 |
| Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011244 | Pregnadienediols |