Cyclosporine Vs Steroids in DRESS

NCT ID: NCT04988256

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-27
• Study Completion Date: 2026-06-30

Brief Summary

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).

Detailed Description

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:

1. fever presence, resolution of facial edema, resolution of pruritus, lymphadenopathy, eosinophil count at days 7 and 30

2. days of hospitalization

3. mortality at days 7, 30 and 90

4. viral reactivation at days 30, 60 and 90

5. those with autoimmune development by day 30 and day 90

6. 30 day re-admission rate.

Conditions

DRESS Syndrome; Drug-Induced Hypersensitivity Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

1. 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

1. If down-trending, start oral taper regimen

2. If not down-trending, switch to steroid arm

4. 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

Group Type: ACTIVE_COMPARATOR

Cyclosporine

Intervention Type: DRUG

Patients randomized to cyclosporine will be treated as mentioned under "Arm/Group Description"

Corticosteroids

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

1. If no improvement, switch to cyclosporine arm of treatment

2. 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:

1. 125 mg IV Methylprednisolone x3 days

2. 1.2 mg/kg PO prednisone x1 week

3. 1 mg/kg PO prednisone x1 week

4. 0.8 mg/kg PO prednisone x1 week

5. 0.6 mg/kg PO prednisone x1 week

6. 0.4 mg/kg PO prednisone x1 week

7. 0.2 mg/kg PO prednisone x1 week

8. 0.1 mg/kg PO prednisone x1 week

9. 0.05 mg/kg PO prednisone x1 week

Group Type: EXPERIMENTAL

Methylprednisolone and Prednisone

Intervention Type: DRUG

All patients randomized to steroids will initially be treated with IV methylprednisolone and eventually started on an oral prednisone taper.

Interventions

Cyclosporine

Patients randomized to cyclosporine will be treated as mentioned under "Arm/Group Description"

Intervention Type: DRUG

Methylprednisolone and Prednisone

All patients randomized to steroids will initially be treated with IV methylprednisolone and eventually started on an oral prednisone taper.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adults with a RegiSCAR score of greater than 4 (i.e a likely diagnosis of DRESS)

Exclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Southern California

OTHER

Sponsor Role: lead

Responsible Party

Scott Worswick

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

USC

Los Angeles, California, United States

Countries

United States

Other Identifiers

HS-20-00118

Identifier Type: -

Identifier Source: org_study_id