Cyclosporine Vs Steroids in DRESS

NCT04988256 | Enrolling By Invitation Early Phase 1 DMC FDA Drug

• 1 other identifier: HS-20-00118
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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).

Conditions

DRESS Syndrome; Drug-Induced Hypersensitivity Syndrome

Outcome Measures

Primary Outcomes (4)

• 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: * 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

  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: * 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

  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

Secondary Outcomes (20)

• Percentage of patients with resolution of fever

  Day 7

• Percentage of patients with resolution of fever

  Day 30

• Percentage of patients with resolution of facial edema

  Day 7

• Percentage of patients with resolution of facial edema

  Day 30

• Percentage of patients with resolution of pruritus

  Day 7

Study Arms (2)

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) 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

Drug: Cyclosporine

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 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

Drug: Methylprednisolone and Prednisone

Interventions

Cyclosporine DRUG

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

Cyclosporine

Methylprednisolone and Prednisone DRUG

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

Corticosteroids

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

USC

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Drug Hypersensitivity Syndrome

Interventions

Cyclosporine; Methylprednisolone; Prednisone

Condition Hierarchy (Ancestors)

Drug Eruptions; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 24, 2021
• First Posted: August 3, 2021
• Study Start: September 27, 2021
• Primary Completion: April 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 30, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)